Recent Advances in Hydroxyapatite-Based Biocomposites for Bone Tissue Regeneration in Orthopedics

Bone tissue is a nanocomposite consisting of an organic and inorganic matrix, in which the collagen component and the mineral phase are organized into complex and porous structures. Hydroxyapatite (HA) is the most used ceramic biomaterial since it mimics the mineral composition of the bone in vertebrates. However, this biomimetic material has poor mechanical properties, such as low tensile and compressive strength, which make it not suitable for bone tissue engineering (BTE). For this reason, HA is often used in combination with different polymers and crosslinkers in the form of composites to improve their mechanical properties and the overall performance of the implantable biomaterials developed for orthopedic applications. This review summarizes recent advances in HA-based biocomposites for bone regeneration, addressing the most widely employed inorganic matrices, the natural and synthetic polymers used as reinforcing components, and the crosslinkers added to improve the mechanical properties of the scaffolds. Besides presenting the main physical and chemical methods in tissue engineering applications, this survey shows that HA biocomposites are generally biocompatible, as per most in vitro and in vivo studies involving animal models and that the results of clinical studies on humans sometimes remain controversial. We believe this review will be helpful as introductory information for scientists studying HA materials in the biomedical field.     

Whole Body Vibration Improves Brain and Musculoskeletal Health by Modulating the Expression of Tissue-Specific Markers: FNDC5 as a Key Regulator of Vibration Adaptations

Whole body vibration (WBV) is well known to exert beneficial effects on multiple tissues, improving synaptic transmission, muscle mass, bone quality, and reducing anxiety and depressive behavior. However, the underlying molecular mechanisms are not yet fully understood, and organs and tissues may respond differently to the vibratory stimulus depending on multiple factors. Therefore, we investigated the WBV effects on the brain and musculoskeletal tissue of 4-month-old young mice, evaluating synaptic plasticity by electrophysiological recordings and tissue organization by histology and histomorphometric analysis. Specifically, WBV protocols were characterized by the same vibration frequency (45 Hz), but different in vibration exposure time (five series of 3 min for the B protocol and three series of 2 min and 30 s for the C protocol) and recovery time between two vibration sessions (1 min for the B protocol and 2 min and 30 s for the C protocol). In addition, immunohistochemistry was conducted to evaluate the expression of fibronectin type III domain-containing protein 5 (FNDC5), as well as that of tissue-specific markers, such as brain-derived neurotrophic factor (BDNF) in brain, myostatin in muscle and collagen I (COL-1) in bone. Our results suggest that the WBV effects depend closely on the type of protocol used and support the hypothesis that different organs or tissues have different susceptibility to vibration. Further studies will be needed to deepen our knowledge of physiological adaptations to vibration and develop customized WBV protocols to improve and preserve cognitive and motor functions.     

PCSK9 Affects Astrocyte Cholesterol Metabolism and Reduces Neuron Cholesterol Supplying In Vitro: Potential Implications in Alzheimer’s Disease

The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) involvement in Alzheimer’s disease (AD) is poorly investigated. We evaluated the in vitro PCSK9 modulation of astrocyte cholesterol metabolism and neuronal cholesterol supplying, which is fundamental for neuronal functions. Moreover, we investigated PCSK9 neurotoxic effects. In human astrocytoma cells, PCSK9 reduced cholesterol content (−20%; p < 0.05), with a greater effect in presence of beta amyloid peptide (Aβ) (−37%; p < 0.01). PCSK9 increased cholesterol synthesis and reduced the uptake of apoE-HDL-derived cholesterol (−36%; p < 0.0001), as well as the LDL receptor (LDLR) and the apoE receptor 2 (ApoER2) expression (−66% and −31%, respectively; p < 0.01). PCSK9 did not modulate ABCA1- and ABCG1-cholesterol efflux, ABCA1 levels, or membrane cholesterol. Conversely, ABCA1 expression and activity, as well as membrane cholesterol, were reduced by Aβ (p < 0.05). In human neuronal cells, PCSK9 reduced apoE-HDL-derived cholesterol uptake (−41%; p < 0.001) and LDLR/apoER2 expression (p < 0.05). Reduced cholesterol internalization occurred also in PCSK9-overexpressing neurons exposed to an astrocyte-conditioned medium (−39%; p < 0.001). PCSK9 reduced neuronal cholesterol content overall (−29%; p < 0.05) and increased the Aβ-induced neurotoxicity (p < 0.0001). Our data revealed an interfering effect of PCSK9, in cooperation with Aβ, on brain cholesterol metabolism leading to neuronal cholesterol reduction, a potentially deleterious effect. PCSK9 also exerted a neurotoxic effect, and thus represents a potential pharmacological target in AD.     

Phenolic composition,antiproliferative and antiulcerogenic activities of a polyphenol-rich purified extract from açai (Euterpe oleracea) fruits

The bioactivity and phytochemical composition of a partially purified extract of açai (PPEA), concentrated in phenolic compounds (PC) and without the presence of macronutrients, were investigated. The major PC quantified by UHPLC-DAD-LTQ-Orbitrap MS-MS/MS in the PPEA are anthocyanins. In vitro, PPEA showed a cytostatic effect on the K-562 lymphoid leukaemia at a concentration of 40 μg PC mL⁻¹, with a GI₅₀ equal to 1.08 μg PC mL⁻¹. In vivo, the extract did not promote acute toxicity in mice in any of the doses tested. The extract displayed gastroprotective activity in rats treated orally with 16, 48 and 160 mg PC kg⁻¹, with a significant decrease in the ulcerative lesion index, compared with the negative control. The lack of toxicity and the bioactivity of the PPEA show that this extract is beneficial to health and useful as a commercial food additive containing natural violet colourant, with pharmaceutical and functional potentials.     

Comments on: Process modeling for slope and aspect with application to elevation data maps

The authors should be commended on their methodological development of stochastic processes for slope and aspect. Their development of basic distribution theory needed to study these two processes, and the sufficient conditions that ensure independence and non-informative induced priors, provide a thorough contribution to the collection of work on gradient processes. The fully model-based approach for inference for slope and aspect enables the propagation of uncertainty to environmental process models of interest that would use these variables as explanatory variables in a regression. I greatly appreciate the opportunity to comment on this exciting work and offer some additional model considerations and applications. Specifically, I reaffirm the importance of scalability of the methodology to large datasets, offering a few considerations with regard to model specification. Next, I discuss the unique challenges of using the predictive distributions of the slope and aspect processes as input variables in spatial regression models. Finally, I offer possible applications and extensions of this work that might provide innovative insights into environmental processes.     

Therapeutic Potential of Antimicrobial Peptides in Polymicrobial Biofilm-Associated Infections

It is widely recognized that many chronic infections of the human body have a polymicrobial etiology. These include diabetic foot ulcer infections, lung infections in cystic fibrosis patients, periodontitis, otitis, urinary tract infections and even a proportion of systemic infections. The treatment of mixed infections poses serious challenges in the clinic. First, polymicrobial communities of microorganisms often organize themselves as biofilms that are notoriously recalcitrant to antimicrobial therapy and clearance by the host immune system. Secondly, a plethora of interactions among community members may affect the expression of virulence factors and the susceptibility to antimicrobials of individual species in the community. Therefore, new strategies able to target multiple pathogens in mixed populations need to be urgently developed and evaluated. In this regard, antimicrobial or host defense peptides (AMPs) deserve particular attention as they are endowed with many favorable features that may serve to this end. The aim of the present review is to offer a comprehensive and updated overview of studies addressing the therapeutic potential of AMPs in mixed infections, highlighting the opportunities offered by this class of antimicrobials in the fight against polymicrobial infections, but also the limits that may arise in their use for this type of application.     

Nanoemulsion as advanced edible coatings to preserve the quality of fresh-cut fruits and vegetables: a review

The increasing consumer's demand regarding the healthy diet has promoted the research towards novel approaches for preserving minimally processed fruits and vegetables without the necessity of using preservatives. Emulsion-based edible coatings technology is considered a valuable alternative to improve fresh-cut fruit and vegetable quality. This review discusses some recent advances for the preservation of the quality and safety of fresh-cut fruits and vegetables with respect to the use of nanoemulsion-based edible coatings as carrier of functional compounds such as antimicrobial agents, antioxidants and texture enhancers. It focuses especially on the use of natural functional compounds in food preservation as an alternative to synthetic additives. Moreover, the preparation and characterisation of nanoemulsion are also reviewed.