Structure elucidation and antiviral activity of a cold water-extracted mannogalactofucan Ts1-1A from Trametes sanguinea against human cytomegalovirus in vitro.

In this study, we purified a partially acetylated heteropolysaccharide (Ts1-1A) from the fruit bodies of Trametes sanguinea Lloyd through cold water extraction and serial chromatographic separation. The purified polysaccharide Ts1-1A (12.8 kDa) was characterized as a branched mannogalactofucan with a backbone of alternately connected 1,3-linked α-Fucp and 1,6-linked α-Galp, which was partially substituted by non-reducing end units of ß-Manp at O-2 and O-3 positions of 1,6-linked α-Galp. Ts1-1A showed pronounced anti-human cytomegalovirus activity at the concentration of 200 and 500 µg/mL in systematical assessments including morphological changes, western blotting, qPCR, indirect immunofluorescence and tissue culture infective dose assays. Moreover, Ts1-1A exerted its antiviral activity at two distinct stages of viral proliferation manifesting as significantly inhibiting viral protein (IE1/2 and p52) expression and reducing viral gene (UL123, UL44 and UL32) replication in the HCMV-infected WI-38 cells. At viral attachment stage, Ts1-1A interacted with HCMV and prevented HCMV from attaching to its host cells. While at early phase of viral replication stage, Ts1-1A suppressed HCMV replication by downregulating NQO1 and HO-1 proteins related to oxidative stress as an antioxidant. To sum up, Ts1-1A is a promising anti-HCMV agent which could be developed for HCMV infection prevention and therapy.

NINJ2 deficiency inhibits preadipocyte differentiation and promotes insulin resistance through regulating insulin signaling.

OBJECTIVE: Genetic variants in ninjurin-2 (NINJ2; nerve injury-induced protein 2) confer risk of ischemic strokes and coronary artery disease as well as endothelial activation and inflammation. However, little is known about NINJ2's in vivo functions and underlying mechanisms. METHODS: The phenotypes of NINJ2 knockout mice were analyzed, and mechanisms of NINJ2 that regulate body weight, insulin resistance, and glucose homeostasis and lipogenesis were investigated in vivo and in vitro. RESULTS: This study found that mice lacking NINJ2 showed impaired adipogenesis, increased insulin resistance, and abnormal glucose homeostasis, all of which are risk factors for strokes and coronary artery disease. Mechanistically, NINJ2 directly interacts with insulin receptor/insulin-like growth factor 1 receptor (INSR/IGF1R), and NINJ2 knockdown can block insulin-induced mitotic clonal expansion during preadipocyte differentiation by inhibiting protein kinase B/extracellular signal-regulated kinase (AKT/ERK) signaling and by decreasing the expression of key adipocyte transcriptional regulators CCAAT/enhancer-binding protein ß (C/EBP-ß), C/EBP-α, and peroxisome proliferator-activated receptor γ (PPAR-γ). Furthermore, the interaction between NINJ2 and INSR/IGF1R is needed for maintaining insulin sensitivity in adipocytes and muscle via AKT and glucose transporter type 4. Notably, adenovirus-mediated NINJ2 overexpression can ameliorate diet-induced insulin resistance in mice. CONCLUSIONS: In conclusion, these findings reveal NINJ2 as an important new facilitator of insulin receptors, and the authors propose a unique regulatory mechanism between insulin signaling, adipogenesis, and insulin resistance.

Three-dimensional assessment of posterior capsule-intraocular lens interaction with and without primary posterior capsulorrhexis: an intraindividual randomized trial.

PURPOSE: To assess the morphologic and clinical features of posterior capsule-intraocular lens (IOL) interaction following cataract surgery with and without primary posterior continuous curvilinear capsulorrhexis (PPCCC) at a three-dimensional (3-D) level using Scheimpflug imaging. METHODS: This prospective intraindividual randomized comparative study comprised 56 patients (112 eyes) with age-related cataract who had bilateral cataract surgery and hydrophobic acrylic IOLs implantation. In randomized order, cataract surgery with PPCCC was performed in 1 eye (PPCCC group), and the posterior capsule was left intact in the fellow eye (NPCCC group). Scheimpflug imaging containing 25 images distributed in 360° was taken 1 day, 1 week, 1 month, and 3 months postoperatively. RESULTS: 46 patients completed 3 months follow-up. Posterior capsule-IOL interaction can be morphologically classified into two types including complete adhesion and floppy shape in PPCCC group, and six types including full area wave, full area flat, concentric ring wave, concentric ring flat, sector, and complete adhesion in NPCCC group. The adhesion index (AI), defined as the proportion of complete adhesion of posterior capsule-IOL in 25 cross-section tomograms, was 0.45 ± 0.45, 0.79 ± 0.37, 0.92 ± 0.26 and 1.00 ± 0.00 in PPCCC group, while 0.05 ± 0.18, 0.41 ± 0.47, 0.87 ± 0.34, and 0.96 ± 0.21 in NPCCC group at 1 day, 1 week, 1 month and 3 months postoperatively, respectively (p = 0.001, 0.001, 0.338 and 0.151). CONCLUSIONS: 3-D Scheimpflug imaging was favorable in observing of posterior capsule-IOL interaction. Faster posterior capsule adhesion to the IOL was found in PPCCC group than in NPCCC group.

Outcomes and Complications of Sutured Scleral-Fixated Foldable Intraocular Lens Implantation: A Retrospective Study of 5-Year Follow-Up.

PURPOSE: To evaluate long-term outcomes and complications of sutured scleral-fixated foldable intraocular lens (IOL) implantation. DESIGN: Retrospective study. METHODS: Patients who underwent sutured scleral-fixated foldable IOL implantation using 10-0 polypropylene suture were followed up for at least 5 years at one Chinese tertiary hospital and two primary hospitals. RESULTS: 52 eyes among 48 patients (35 male and 13 female) were evaluated. The mean age (years) was 50.27 ± 20.08 (range: 6 to 81). The mean postoperative follow-up time (months) was 79.70 ± 18.84 (range: 60 to 121). The mean best-corrected visual acuity (BCVA) improved from 0.83 ± 0.69 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.50 ± 0.45 logMAR at the last follow-up visit. There was improved or unchanged BCVA in 44 eyes (84.62%) and reduced BCVA in 8 eyes (15.38%). Mild intraoperative intravitreal hemorrhage was observed in 3 eyes (5.77%). Early postoperative complications included transient elevated intraocular pressure (IOP) in 5 eyes (9.62%) and hypotony in 1 eye (1.92%). Secondary epimacular membrane occurred in 5 eyes (9.62%) and retinal detachment (RD; 3 years postsurgery), subconjunctival suture knot exposure (5 years postsurgery), and persistent elevated IOP (in a GRAVES patient) occurred in 1 eye (1.92%) each. No suture erosion or breakage nor IOL dislocation was observed. No visually threatening IOL tilt or decentration was reported in any patient. CONCLUSION: Sutured scleral-fixated foldable IOL implantation demonstrated satisfactory long-term outcomes and rare suture-related complications. This technology was safe and did not require complicated equipment and is of considerable interest in the setting of aphakia without adequate capsule support.