Bone loss recovery in mice following microgravity with concurrent bone-compartment-specific osteocyte characteristics

Space missions provide the opportunity to investigate the influence of gravity on the dynamic remodelling processes in bone. Mice were examined following space flight and subsequent recovery to determine the effects on bone compartment-specific microstructure and composition. The resulting bone loss following microgravity recovered only in trabecular bone, while in cortical bone the tissue mineral density was restored after only one week on Earth. Detection of TRAP-positive bone surface cells in the trabecular compartment indicated increased resorption following space flight. In cortical bone, a persistent reduced viability of osteocytes suggested an impaired sensitivity to mechanical stresses. A compartment-dependent structural recovery from microgravity-induced bone loss was shown, with a direct osteocytic contribution to persistent low bone volume in the cortical region even after a recovery period. Trabecular recovery was not accompanied by changes in osteocyte characteristics. These post-space-flight findings will contribute to the understanding of compositional changes that compromise bone quality caused by unloading, immobilisation, or disuse.

The Role of Hyaluronic Acid in Sport-Related Tendinopathies: A Narrative Review

Tendinopathy is a complex clinical condition with a rising incidence and prevalence, particularly during sports practice. For the return to play in affected patients, adequate functional and structural recovery of the tendon is the ultimate goal, avoiding the high risk of recurrence. In this perspective, local therapies alongside exercise are showing promising results. Despite evidence suggesting hyaluronic acid (HA) injections as effective in the treatment of tendinopathy, current recommendations about the management of this condition do not include this intervention. HA seems to be an effective therapeutic option for the management of sport-related tendinopathies, but further studies with a larger sample size are needed to confirm available findings. In this narrative review, we analyzed available literature about the rationale of the use of HA in the management of tendon injury and, particularly, in sport-related tendinopathies.

Changes of Visual Acuity and Macular Thickness after Phacovitrectomy with Posterior Capsulectomy of Epiretinal Membrane

Purpose: To investigate the functional and structural recovery period of idiopathic epiretinal membranes after phacovitrectomy with posterior capsulectomy.Methods: From March 2012 to January 2015, 57 patients diagnosed with idiopathic epiretinal membranes with cataracts who underwent combined vitrectomy and cataract surgery with pars plana posterior capsulectomy were enrolled. The best-corrected visual acuity and central foveal thickness were analyzed retrospectively.Results: The average best-corrected visual acuity before surgery was 0.30 ± 0.23 logarithm of minimal angle of resolution (logMAR), and the mean central foveal thickness was 442 ± 93 μm. As of the 12-month follow-up, the average postoperative best-corrected visual acuity had improved to 0.08 ± 0.11 logMAR, and the central foveal thickness after surgery had decreased to 386 ± 58 μm at 12 months.Conclusions: After removing the potential influence of cataracts and posterior capsular opacity, the recovery of idiopathic epiretinal membranes continued up to 12 months after surgery.

Bioactive Electrospun Fibers of Poly(ε-Caprolactone) Incorporating α-Tocopherol for Food Packaging Applications

Antioxidant activity is an important feature for food contact materials such as packaging, aiming to preserve freshness and retard food spoilage. Common bioactive agents are highly susceptible to various forms of degradation; therefore, protection is required to maintain functionality and bioavailability. Poly(ε-caprolactone) (PCL), a biodegradable GRAS labeled polymer, was used in this study for encapsulation of α-tocopherol antioxidant, a major component of vitamin E, in the form of electrospun fibers. Rheological properties of the fiber forming solutions, which determine the electrospinning behavior, were correlated with the properties of electrospun fibers, e.g., morphology and surface properties. Interactions through hydrogen bonds were evidenced between the two components. These have strong effect on structuration of macromolecular chains, especially at low α-tocopherol amounts, decreasing viscosity and elastic modulus. Intra-molecular interactions in PCL strengthen at high α-tocopherol amounts due to decreased solvation, allowing good structural recovery after cease of mechanical stress. Morphologically homogeneous electrospun fibers were obtained, with ~6 μm average diameter. The obtained fibers were highly hydrophobic, with fast release in 95% ethanol as alternative simulant for fatty foods. This induced good in vitro antioxidant activity and significant in vivo reduction of microbial growth on cheese, as determined by respirometry. Therefore, the electrospun fibers from PCL entrapping α-tocopherol as bioactive agent showed potential use in food packaging materials.

Macrophages stimulate epicardial VEGFaa to trigger cardiomyocyte proliferation in larval zebrafish heart regeneration

Cardiac injury induces a sustained innate immune response in both zebrafish and mammals. Macrophages, highly plastic immune cells, perform a range of both beneficial and detrimental functions during mammalian cardiac repair yet their precise roles in zebrafish cardiac regeneration are not fully understood. Here we characterise cardiac regeneration in the rapidly regenerating larval zebrafish laser injury model and use macrophage ablation and macrophage-less irf8 mutants to define the requirement of macrophages for key stages of regeneration. We found macrophages to display cellular heterogeneity and plasticity in larval heart injury as in mammals. Live heartbeat-synchronised imaging and RNAseq revealed an early proinflammatory macrophage phase which then resolves to an anti-inflammatory, profibrotic phase. Macrophages are required for cardiomyocyte proliferation but not for functional or structural recovery following injury. Macrophages are specifically recruited to the epicardial-myocardial niche, triggering the expansion of the epicardium which upregulates mitogen VEGFaa. Experimental perturbation of VEGF signalling confirmed VEGFaa to be an important inducer of cardiomyocyte proliferation revealing a previously unrecognised mechanism by which macrophages aid cardiac regeneration.

Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of Autophagy and Immune Response

Traumatic spinal cord injury (SCI) is untreatable and remains the leading cause of disability. Neuroprotection and recovery after SCI can be partially achieved by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian target of rapamycin (mTOR) pathway. However, mechanisms regulated by the mTOR pathway are not only controlled by mTORC1, but also by a second mTOR complex (mTORC2). Second-generation inhibitor, pp242, inhibits both mTORC1 and mtORC2, which led us to explore its therapeutic potential after SCI and compare it to RAPA treatment. In a rat balloon-compression model of SCI, the effect of daily RAPA (5 mg/kg; IP) and pp242 (5 mg/kg; IP) treatment on inflammatory responses and autophagy was observed. We demonstrated inhibition of the mTOR pathway after SCI through analysis of p-S6, p-Akt, and p-4E-BP1 levels. Several proinflammatory cytokines were elevated in pp242-treated rats, while RAPA treatment led to a decrease in proinflammatory cytokines. Both RAPA and pp242 treatments caused an upregulation of LC3B and led to improved functional and structural recovery in acute SCI compared to the controls, however, a greater axonal sprouting was seen following RAPA treatment. These results suggest that dual mTOR inhibition by pp242 after SCI induces distinct mechanisms and leads to recovery somewhat inferior to that following RAPA treatment.