Bouzid Menaa

Graphene nanomaterials as biocompatible and conductive scaffolds for stem cells: impact for tissue engineering and regenerative medicine

The discovery of the interesting intrinsic properties of graphene, a two‐dimensional nanomaterial, has boosted further research and development for various types of applications from electronics to biomedicine. During the last decade, graphene and several graphene‐derived materials, such as graphene oxide, carbon nanotubes, activated charcoal composite, fluorinated graphenes and three‐dimensional graphene foams, have been extensively explored as components of biosensors or theranostics, or to remotely control cell–substrate interfaces, because of their remarkable electro‐conductivity. To date, despite the intensive progress in human stem cell research, only a few attempts to use carbon nanotechnology in the stem cell field have been reported. Interestingly, most of the recent in vitro studies indicate that graphene‐based nanomaterials (i.e. mainly graphene, graphene oxide and carbon nanotubes) promote stem cell adhesion, growth, expansion and differentiation. Although cell viability in vitro is not affected, their potential nanocytoxicity (i.e. nanocompatibility and consequences of uncontrolled nanobiodegradability) in a clinical setting using humans remains unknown. Therefore, rigorous internationally standardized clinical studies in humans that would aim to assess their nanotoxicology are requested. In this paper we report and discuss the recent and pertinent findings about graphene and derivatives as valuable nanomaterials for stem cell research (i.e. culture, maintenance and differentiation) and tissue engineering, as well as for regenerative, translational and personalized medicine (e.g. bone reconstruction, neural regeneration). Also, from scarce nanotoxicological data, we also highlight the importance of functionalizing graphene‐based nanomaterials to minimize the cytotoxic effects, as well as other critical safety parameters that remain important to take into consideration when developing nanobionanomaterials. Copyright

Bioencapsulation of apomyoglobin in nanoporous organosilica sol–gel glasses: Influence of the siloxane network on the conformation and stability of a model protein

Nanoporous sol-gel glasses were used as host materials for the encapsulation of apomyoglobin, a model protein employed to probe in a rational manner the important factors that influence the protein conformation and stability in silica-based materials. The transparent glasses were prepared from tetramethoxysilane (TMOS) and modified with a series of mono-, di- and tri-substituted alkoxysilanes, R(n)Si(OCH(3))(4-n) (R = methyl-, n = 1; 2; 3) of different molar content (5, 10, 15%) to obtain the decrease of the siloxane linkage (-Si-O-Si-). The conformation and thermal stability of apomyoglobin characterized by circular dichroism spectroscopy (CD) was related to the structure of the silica host matrix characterized by (29)Si MAS NMR and N(2) adsorption. We observed that the protein transits from an unfolded state in unmodified glass (TMOS) to a native-like helical state in the organically modified glasses, but also that the secondary structure of the protein was enhanced by the decrease of the siloxane network with the methyl modification (n = 0 < n = 1 < n = 2 < n = 3; 0 < 5 < 10 < 15 mol %). In 15% trimethyl-modified glass, the protein even reached a maximum molar helicity (-24,000 deg. cm(2) mol(-1)) comparable to the stable folded heme-bound holoprotein in solution. The protein conformation and stability induced by the change of its microlocal environment (surface hydration, crowding effects, microstructure of the host matrix) were discussed owing to this trend dependency. These results can have an important impact for the design of new efficient biomaterials (sensors or implanted devices) in which properly folded protein is necessary.

Trans-fatty acids, dangerous bonds for health? A background review paper of their use, consumption, health implications and regulation in France

IntroductionTrans-fatty acids (TFAs) can be produced either from bio-hydrogenation in the rumen of ruminants or by industrial hydrogenation. While most of TFAs’ effects from ruminants are poorly established, there is increasing evidence that high content of industrial TFAs may cause deleterious effects on human health and life span.Material and methodsIndeed, several epidemiological and experimental studies strongly suggest that high content of most TFA isomers could represent a higher risk of developing cardiovascular diseases by a mechanism that lowers the “good HDL cholesterol” and raises the “bad LDL cholesterol.”ResultsWith respect to the general precautionary principle and considering the existence of an international policy consensus regarding the need for public health action, some industrialized countries, such as France, are still not sufficiently involved in preventive strategies that aim to efficiently reduce TFAs content and TFAs consumption and produce alternative healthier fat sources.ConclusionIn this manuscript, we provide an overview about TFAs origins, their use and consumption among French population. We also discuss their potential human health implications as well as the preventive and regulatory measures undertaken in France.

Technological Approaches to Minimize Industrial Trans Fatty Acids in Foods

Trans fatty acids (TFAs) mainly arise from 2 major sources: natural ruminal hydrogenation and industrial partial catalytic hydrogenation. Increasing evidence suggests that most TFAs and their isomers cause harmful health effects (that is, increased risk of cardiovascular diseases). Nevertheless, in spite of the existence of an international policy consensus regarding the need for public health action, several countries (for example, France) do not adopt sufficient voluntary approaches (for example, governmental regulations and systematic consumer rejections) nor sufficient industrial strategies (for example, development of healthier manufacturing practices and innovative processes such as fat interesterifications) to eliminate deleterious TFAs from processed foods while ensuring the overall quality of the final product (for example, nutritional value and stability). In this manuscript, we first review the physical-chemical properties of TFAs, their occurrence in processed foods, their main effects on health, and the routine analytical methods to characterize TFAs, before emphasizing on the major industrial methods (that is, fat food reformulation, fat interesterification, genetically modified FAs composition) that can be used worldwide to reduce TFAs in foods.

Keeping an eye on myocilin: a complex molecule associated with primary open-angle glaucoma susceptibility.

MYOC encodes a secretary glycoprotein of 504 amino acids named myocilin. MYOC is the first gene to be linked to juvenile open-angle glaucoma (JOAG) and some forms of adult-onset primary open-angle glaucoma (POAG). The gene was identified as an up-regulated molecule in cultured trabecular meshwork (TM) cells after treatment with dexamethasone and was originally referred to as trabecular meshwork-inducible glucocorticoid response (TIGR). Elevated intraocular pressure (IOP), due to decreased aqueous outflow, is the strongest known risk factor for POAG. Increasing evidence showed that the modulation of the wild-type (wt) myocilin protein expression is not causative of glaucoma while some misfolded and self-assembly aggregates of mutated myocilin may be associated with POAG in related or unrelated populations. The etiology of the disease remains unclear. Consequently, a better understanding of the molecular mechanisms underlyingPOAG is required to obtain early diagnosis, avoid potential disease progression, and develop new therapeutic strategies. In the present study, we review and discuss the most relevant studies regarding structural characterizations, expressions, molecular interactions, putative functions of MYOC gene and/or its corresponding protein in POAG etiology.

Protein Adsorption onto Organically Modified Silica Glass Leads to a Different Structure than Sol-Gel Encapsulation ☆

The secondary structures of two proteins were examined by circular dichroism spectroscopy after adsorption onto a series of organically modified silica glasses. The glasses were prepared by the sol-gel technique and were varied in hydrophobicity by incorporation of 5% methyl, propyl, trifluoropropyl, or n-hexyl silane. Both cytochrome c and apomyoglobin were found to lose secondary structure after adsorption onto the modified glasses. In the case of apomyoglobin, the alpha-helical content of the adsorbed protein ranged from 21% to 28%, well below the 62% helix found in solution. In contrast, these same glasses led to a striking increase in apomyoglobin structure when the protein was encapsulated within the pores during sol-gel processing: the helical content of apomyoglobin increased with increasing hydrophobicity from 18% in an unmodified glass to 67% in a 5% hexyl-modified glass. We propose that proteins preferentially adsorb onto unmodified regions of the silica surface, whereas encapsulated proteins are more susceptible to changes in surface hydration due to the proximity of the alkyl chain groups.

Importance of Fluorine and Fluorocarbons in Medicinal Chemistry and Oncology

Carbon-Fluorine (C-F) can serve as a molecular tag for many applications in medicinal chemistry and oncology such as identification (i.e. screening), imaging (i.e. tracing) and analytical characterization. Thereby, fluorination, a chemical process to add a fluorine atom into a single molecule or a complex matrix materials (e.g. compounds) is largely used in the pharmaceutical field to confer some interesting properties to cancer drug compounds (e.g. enhancement of bioavailability). It is further more recently used for labelling some biological molecules of interest (i.e. peptides, nucleic acids) or nanomaterials (i.e. nanoparticles) which are of high importance for cancer chemoand biotherapy (e.g. immunotherapy) as well as for tumor (aka tumour)/cancer imaging (i.e. staging/prognosis, biodistribution, cancer diagnosis and therapy). Indeed, In addition to be easy-to-handle, efficient, soluble, smaller and cheaper, C-F bond is more stable than fluorescent dye, less toxic than fluorine radioisotopes, and less harmful than radio-waves. We have developed a patented technology called carbon-fluorine spectroscopy (CFS aka Spectro-Fluor®) along with methods and applications to not only specifically and sensitively detect C-F bonds in raw pure compound, complex materials but also to screen (e.g. drug discovery and drug security) as well as to trace F-molecules in vivo for improved medical care, particularly but not limited to the oncology sector (e.g. tumor/cancer imaging, development of new F- reagents, F-biomolecules, and anti-cancer agents). In this paper, we reviewed and discussed the major physical-chemical properties of C-F bond, the main applications of fluorocarbons as well as the state-of-art imaging technologies that use fluorine for clinical and research and development (R&D) oncology purposes (e.g. drug design, drug discovery, drug delivery and molecular imaging). An emphasis is put on the use of safer, unlabeled fluorinated molecules thanks to the emerging and promising CFS derived platform green technology that allows to reliably detecting unlabeled C-F molecules. Overall, we conclude that fluorine is a magical atom for molecular diagnosis and therapy that does not always need to be labelled.

Promising Plant Extracts with In Vivo Anti-melanoma Potential

Melanoma is a highly aggressive, therapy-resistant skin cancer, representing an increasing health problem due to its complex etiology, heterogeneity, and modest results obtained with the current treatment options. Development of targeted bioactive phytochemicals as therapeutics might provide better choices for melanoma tumor regression and enhancement in patient’s survival. Therefore, the constant search for alternative drugs that are effective, specific, and nontoxic in the treatment of melanoma is required and encouraged. Very few, but emerging studies, mainly published during the last decade, purposed that some plant extracts, contain effective and low-adverse effects anti-melanoma drug. In this review, based on the relevant literature and relatively recent in vivo studies using melanoma-bearing animal models, we report five most plant extracts which are promising in the prevention and/or the treatment of melanoma.

Dietary Intake of (-)-Epigallocatechin-3-gallate against Aging and Cancers: Nanoencapsulation of Multi- Rings Still Requires New Rounds!

Dietary Intake of (-)-Epigallocatechin-3-gallate against Aging and Cancers: Nanoencapsulation of Multi- Rings Still Requires New Rounds! Polyphenols, a superfamily of naturally occurring phytochemicals, are gaining popularity because of their potential health benefits. Indeed, as demonstrated in ex-vivo and in non-primates models, they exert variable and pleiotropic biological effects (e.g. anti- or pro-oxidant, anti-inflammatory, anti-tumoral, anti-aging) depending on their structure and physicochemical features. However, these effects are often limited Carnauba wax by their overall unstability and bioavailability. The fact that some polyphenols act either as anti-oxidants (e.g. against aging) or as pro-oxidants (e.g. against tumors/cancers), remain an unsolved paradigm. Interestingly, emergent studies suggest that nano-encapsulated polyphenols might overcome some limitations frequently observed with dietary bulk-polyphenols (e.g. bioavailability, pharmacokinetics, targeting, efficacy, toxicity and safety), subsequently potentiating their biological effects. In this context, the case of (-)-epigallocatechin- 3-gallate (EGCG) is quite intriguing.

Protein helical structure enhancement in biocompatible fluoro-phosphonate-based nanoporous silica glasses assessed by circular dichroism spectroscopy

The role of fluorine and phosphonate groups on protein structure and biocompatibility has been probed by protein encapsulation in tetramethoxysilane (TMOS)-based sol-gel glass and assessed by circular dichroism spectroscopy (CD). Apomyoglobin (apoMb) is known as a model protein for the study of protein folding. Thus, we demonstrated the increase of apoMb helicity in phosphonate and fluorinated phosphonate-based sol-gel glasses via the addition of methane diphosphonic acid (MDPA) and difluoromethane diphosphonic acid (DFMDPA) during the hydrolysis/polycondensation of TMOS precursor forming a nanoporous sol-gel glass host matrix for the protein. Alternatively to silica surface functionalisation using organosilane modifiers, functional organic molecules or nano-agents can be doped directly during the sol-gel process. Since TMOS is not functionalised, we can probe the role of some organic molecules as intermediates as well as their surface hydration effect contributing to the protein folding process. The presence of both fluorine and phosphonate groups in TMOS glass folded the protein to its native state as function of its molar content. The protein ellipticity has been enlightened by CD with signals observable at 222 nm characterising the secondary protein structure at the far UV. The incorporation of these groups to the sol-gel glass systems to mimic the behaviour and conformation of protein as function of its surrounding environment brings both steric and hydrophobic properties to enhance the protein folding. These results are important from the point of view of potential applications in bio-nanotechnology with the design of efficient biomaterials but also to probe the role of fluorine and phosphonate groups in protein folding for the human healthcare.