Bacteria can produce cellulose, one of the most abundant biopolymer on earth, and emerge as an interesting candidate to fabricate advanced materials. Cellulose produced by Komagataeibacter Xylinus, a bacterial strain, is a pure water insoluble biopolymer, without hemicellulose or lignin. Bacterial cellulose (BC) exhibits a nanofibrous porous network microstructure with high strength, low density and high biocompatibility and it has been proposed as cell scaffold and wound healing material. The formation of three dimensional (3D) cellulose self-standing structures is not simple. It either involves complex multi-step synthetic procedures or uses chemical methods to dissolve cellulose and remold it. Here we present an in situ single-step method to produce self-standing 3D-BC structures with controllable wall thickness, size and geometry in a reproducible manner. Parameters such as hydrophobicity of the surfaces, volume of the inoculum and time of culture define the resulting 3D-BC structures. Hollow spheres and convex domes can be easily obtained by changing the surface wettability. The potential of these structures as a 3D cell scaffold is exemplified supporting the growth of mouse embryonic stem cells within a hollow spherical BC structure, indicating its biocompatibility and future prospective.

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Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases).

Actuated structures are becoming relevant in medical fields; however, they call for flexible/soft-base materials that comply with biological tissues and can be synthesized in simple fabrication steps. In this work, we extend the palette of techniques to afford soft, actuable spherical structures taking advantage of the biosynthesis process of bacterial cellulose. Bacterial cellulose spheres (BCS) with localized magnetic nanoparticles (NPs) have been biosynthesized using two different one-pot processes: in agitation and on hydrophobic surface-supported static culture, achieving core-shell or hollow spheres, respectively. Magnetic actuability is conferred by superparamagnetic iron oxide NPs (SPIONs), and their location within the structure was finely tuned with high precision. The size, structure, flexibility and magnetic response of the spheres have been characterized. In addition, the versatility of the methodology allows us to produce actuated spherical structures adding other NPs (Au and Pt) in specific locations, creating Janus structures. The combination of Pt NPs and SPIONs provides moving composite structures driven both by a magnetic field and a H2O2 oxidation reaction. Janus Pt/SPIONs increased by five times the directionality and movement of these structures in comparison to the controls.

Background Alzheimer’s disease (AD) is a neurodegenerative disease with as yet no efficient therapies. Many drugs and therapies have been designed and developed against this neurodegenerative disease, although none has successfully terminated a phase‐III clinical trial in humans. To shift the perspective for the design of new AD therapies, membrane lipid therapy has been tested, which assumes that brain lipid alterations lie upstream in the pathophysiology of AD. A hydroxylated derivative of docosahexaenoic acid was used, 2‐hydroxy‐docosahexaenoic acid (DHA‐H), which has shown efficacy against hallmarks of AD pathology in a transgenic mouse model of AD (5xFAD). Method Lipid samples were obtained from cultured cells and blood plasma and brain from WT and 5xFAD mice. Both, cell cultures and animals were treated with DHA‐H and DHA under different conditions. Mice were subjected to the Radial Arm Maze test during the last month of treatment just before sacrifice. Fatty acid analysis was performed by GC‐FID and GC‐MS (Gas Chromatography‐Flame Ionization Detector and ‐Mass Spectrometry) and the lipidomic analysis carried out by ESI‐MS (Electrospray ionization‐Mass Spectrometry). Result Here, for the first time, DHA‐H is shown to undergo α‐oxidation to generate the heneicosapentaenoic acid (HPA, C21:5, n‐3) metabolite, an odd‐chain omega‐3 polyunsaturated fatty acid that accumulates in cell cultures, mouse blood plasma and brain tissue upon DHA‐H treatment. Interestingly, DHA‐H does not share metabolic routes with its natural analog DHA (C22:6, n‐3) but rather, DHA‐H and DHA accumulate distinctly, both having different effects on cell fatty acid composition. This is partly explained because DHA‐H α‐hydroxyl group provokes steric hindrance on fatty acid carbon 1, which in turn leads to diminished uptake by cultured cells and accumulation as free fatty acid in cell membranes. Finally, DHA‐H administration to mice elevated the brain HPA levels which in turn were directly and positively correlated with cognitive spatial scores in AD mice. This effect appeared in the apparent absence of DHA‐H and without any significant change DHA levels in brain. Conclusion The evidence presented in this work suggest that the metabolic conversion of DHA‐H into HPA could represent a key event in the therapeutic effects of DHA‐H against AD.

Background DHA‐H (Hydroxy‐docosahexaenoic acid) is a molecule in development for Alzheimer’s disease (AD) treatment based on the concept of membrane lipid therapy (melitherapy). Once entered the cell, DHA‐H is metabolized via α‐oxidation to the fatty acid HPA (Heneicosapentaenoic acid). DHA‐H has been shown to reduce the amyloidogenic processing of Amyloid Precursor Protein (APP), as well as having a neuroprotective effect in cellular models. Although the mechanism of action of DHA‐H is not yet fully understood, results obtained in excitotoxicity models and lipid profile analysis suggest that HPA could be a DHA‐H effector. Methods : APP processing was assessed in cell cultures of HEK293 and N2a neuroblastoma cell lines and analyzed by western blot. Neuroprotective effect of DHA‐H and HPA was tested in neuron cells differentiated from SH‐SY5Y neuroblastoma cells that were stimulated with NMDA (N‐Methyl‐D‐Aspartate)/Ca to induce excitotoxicity. Lipid samples for lipid profile analysis were obtained from the same cultured cells by addition of chloroform/methanol. Fatty acids were transformed into methyl esters and analyzed by GC‐FID (Gas Chromatography‐Flame ionization detector). Results : DHA‐H administration decreases the levels of derivatives from the APP amyloidogenic processing. DHA‐H and HPA showed a neuroprotective effect in a neuronal model of NMDA‐induced excitotoxicity. DHA‐H administration does not significantly alter the main fatty acids but clearly increases HPA levels in the cells. Conclusion All these results together demonstrate that DHA‐H exerts neuroprotection and prevents amyloidogenic processing possibly through its metabolic intermediate HPA. Therefore, HPA appears as a new promising molecule for Alzheimer’s therapy.

Background DHA‐H (2‐hydroxy‐docosahexaenoic acid) is a promising therapeutic approach for Alzheimer’s Disease (AD). DHA‐H gives rise to dose‐dependent increased levels of HPA (Heneicosapentaenoic acid) in blood plasma and brain whereas DHA‐H remains virtually absent from the brain of DHA‐H‐treated mice. Oral administration of DHA‐H to a transgenic model of AD (5xFAD mice) induces a significative cognitive recovery. However, the molecular mechanism underlying this neuroprotective effect remains largely unresolved. Method Screening of potential receptors for DHA‐H and HPA was performed using computational tools. PPARG (Peroxisome Proliferator‐Activated Receptor γ) activity was determined by cell‐based assays. Levels of proteins involved in amyloid production as well as synaptic markers were determined by WB and/or ELISA. β‐ and γ‐secretase activities were measured in cell‐free assays. Neuronal density was determined by immunohistochemistry. Brain levels of DHA‐H and HPA were determined by Electrospray Ionization – Mass Spectrometry (ESI‐MS). Result Both DHA‐H and HPA are activators of PPARG. We have analyzed the effect of DHA‐H treatment on the amyloidogenic route in the 5xFAD mice and this effect was related with PPARG activity. We observed a modulation of protein levels and enzymatic activities involved in β‐amyloid production as well as a prevention of synaptic and neuron degeneration in DHA‐H‐treated mice as compared with untreated controls. These changes were related with improved cognitive scores in these mice. Conclusion All these results together indicate that DHA‐H administration must prevent neuronal degeneration and cognitive decline in AD mice through its immediate metabolite HPA and without apparent involvement of PPARG.