Matters of size: Roles of hyaluronan in CNS aging and disease

Involvement of extracellular matrix (ECM) components in aging and age-related neurodegeneration is not well understood. The role of hyaluronan (HA), a major extracellular matrix glycosaminoglycan, in malignancy and inflammation is gaining new understanding. In particular, the differential biological effects of high molecular weight (HMW-HA) and low molecular weight hyaluronan (LMW-HA), and the mechanism behind such differences are being uncovered. Tightly regulated in the brain, HA can have diverse effects on cellular development, growth and degeneration. In this review, we summarize the homeostasis and signaling of HA in healthy tissue, discuss its distribution and ontogeny in the central nervous system (CNS), summarize evidence for its involvement in age-related neurodegeneration and Alzheimer Disease (AD), and assess the potential of HA as a therapeutic target in the CNS.     

Protective immunity against influenza virus challenge by norovirus P particle-M2e and HA2-AtCYN vaccines in chickens

Development of a broadly reactive influenza vaccine that can provide protection against emerging type A influenza viruses is a big challenge. We previously demonstrated that a vaccine displaying the extracellular domain of the matrix protein 2 (M2e) on the surface loops of norovirus P-particle (M2eP) can partially protect chickens against several subtypes of avian influenza viruses. In the current study, a chimeric vaccine containing a conserved peptide from the subunit 2 of hemagglutinin (HA) glycoprotein (HA2) and Arabidopsis thaliana cyanase protein (AtCYN) (HA2-AtCYN vaccine) was evaluated in 2-weeks-old chickens. Depending on the route of administration, the HA2-AtCYN vaccine was shown to induce various levels of HA2-specific IgA in tears as well as serum IgG, which were associated with partial protection of chickens against tracheal shedding of a low pathogenicity H5N2 challenge virus. Furthermore, intranasal administration with a combination of HA2-AtCYN and M2eP vaccines resulted in enhanced protection compared to each vaccine alone. Simultaneous intranasal administration of the vaccines did not interfere with secretory IgA induction by each vaccine. Additionally, significantly higher M2eP-specific proliferative responses were observed in peripheral blood mononuclear cells of all M2eP-vaccinated groups when compared with the mock-vaccinated group. Although tripling the number of M2e copies did not enhance the protective efficacy of the chimeric vaccine, it significantly reduced immunodominance of P-particle epitopes without affecting the robustness of M2e-specific immune responses. Taken together, our data suggests that mucosal immunization of chickens with combinations of mechanistically different cross-subtype-conserved vaccines has the potential to enhance the protective efficacy against influenza virus challenge.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6–59 months of age: A phase 3, randomized,noninferiority study

Background

In the Southern Hemisphere 2010 influenza season, Seqirus’ split-virion, trivalent inactivated influenza vaccine was associated with increased reports of fevers and febrile reactions in young children. A staged clinical development program of a quadrivalent vaccine (Seqirus IIV4 [S-IIV4]; Afluria® Quadrivalent/Afluria Quad?/Afluria Tetra?), wherein each vaccine strain is split using a higher detergent concentration to reduce lipid content (considered the cause of the increased fevers and febrile reactions), is now complete.

Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface

The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury.     

Radioembolization with yttrium-90 microspheres work up: Practical approach and literature review

Radioembolization (RE) is a selective internal radiotherapy technique in which yttrium-90 blended microspheres are infused through the hepatic arteries. It is based on the fact that primary and secondary hepatic tumors are vascularized mostly by arterial blood flow whereas healthy hepatocytes obtain their blood supply mostly from the portal network. This enables high radiation doses to be delivered, sparing the surrounding non-malignant liver parenchyma. Most of the complications are caused by unexpected particles passing into the gastrointestinal tract through branches originating from the main hepatic arterial supply. Knowledge of this hepatic arterial network and of its variations and the technical considerations this raises are required in preparation for treatment. This work describes the specific anatomical features and techniques for this anatomy through recent literature illustrated by cases from our own experience.     

引导组织再生术与骨移植联合治疗根分叉病变

目的:以牙周引导再生术(GTR)观察胶原膜与Bio-Oss和HA联合治疗Ⅱ～Ⅲ度根分叉病变的疗效。方法:选53例根分叉区病变的患牙65个,分HA GTR及Bio-Oss GTR二组,术后以定性及定量指标对比分析疗效。结果:与术前相比两组术后牙周袋深度(PD)、根分叉水平探入深度(HPD)、附着丧失(AL)、牙龈指数(GI)均明显减少,且有显著性差异(P<0.05);Bio-Oss GTR组PD值低于HA GTR组(P<0.05)。两组骨缺损处均有明显新生牙槽骨。结论:Bio-Oss和HA联合GTR治疗Ⅱ～Ⅲ度根分叉病变,可获得良好的临床疗效,Bio-Oss稍优于HA。     

骨髓间质干细胞介导用于颌面整形的动物实验研究

目的体外扩增小型猪骨髓间质干细胞(bone marrow derived mesenchymal stem cells,BMMSCs),研究其介导颌面整形的可行性.方法分离培养小型猪BMMSCs,扩增后接种到预制的羟基磷灰石/磷酸三钙(hydroxyapatite/tricalcium phosphate,HA/TCP)材料上,分别自体回植入小型猪额骨骨膜下,定期行X线、CT检查.术后12周和20周分别处死动物,取材后进行组织学和扫描电镜检查分析.结果动物额部外形术后明显改变.植入之BMMSCs-HA/TCP复合体与额骨表面紧密融合,强度似骨,复合体内广泛分布着新生骨组织,成骨性好.结论经培养扩增的BMMSCs与HA/TCP复合植入额骨骨膜下在额骨表面形成骨组织,可用来改变面部形态,为颌面整形治疗提供了新的思路.     

Functionalized Polycaprolactone/Hydroxyapatite Composite Microspheres for Promoting Bone Consolidation in a Rat Distraction Osteogenesis Model

Distraction osteogenesis (DO) is an ideal model to study bone regeneration. The major limitation is the relatively long period required for new bone consolidation. Here, we investigated whether the application of polycaprolactone (PCL) and hydroxyapatite (HA) composite microspheres could enhance bone formation in DO. Pure PCL microspheres and composite PCL and 10% HA microspheres were synthesized. Bone mesenchymal stem cells isolated from green fluorescent protein rats (GFP-rBMSCs) were cultured with microspheres in a rotary bioreactor system. Scanning electron microscopy was used to examine the microstructures. Osteogenic differentiation of rBMSCs was confirmed. Moreover, PCL/HA (20 mg) and PCL (20 mg) were locally administered into the distraction gap in the rat DO model toward the end of the distraction period. Imaging detection, mechanical and histological examinations were performed to assess the quality of the 4-week regenerates. Results showed that the microspheres were of uniform size and monodisperse. After incubation with rBMSCs in culture, PCL/HA microspheres showed a better ability for cell adhesion and osteogenic differentiation compared with PCL microspheres. In vivo, bone volume/total tissue volume, bone mineral density, and mechanical properties of the new callus were significantly higher in the PCL/HA group compared with the PCL group. Histological analyses confirmed improved bone formation and vascularization in PCL/HA group. We presented an effective protocol for the generation of functionalized microspheres and demonstrated implantation of PCL/HA microspheres into the distraction regenerate could significantly enhance bone consolidation. Thus, the application of PCL/HA composite microspheres may be a novel approach for promoting bone regeneration. This article is protected by copyright. All rights reserved © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:961-971, 2020