Marine Algae-Derived Bioactive Compounds: A New Wave of Nanodrugs?

Marine algae are rich in bioactive nutraceuticals (e.g., carbohydrates, proteins, minerals, fatty acids, antioxidants, and pigments). Biotic (e.g., plants, microorganisms) and abiotic factors (e.g., temperature, pH, salinity, light intensity) contribute to the production of primary and secondary metabolites by algae. Easy, profitable, and sustainable recovery methods include novel solid-liquid and liquid-liquid extraction techniques (e.g., supercritical, high pressure, microwave, ultrasound, enzymatic). The spectacular findings of algal-mediated synthesis of nanotheranostics has attracted further interest because of the availability of microalgae-based natural bioactive therapeutic compounds and the cost-effective commercialization of stable microalgal drugs. Algal extracts can serve as stabilizing/capping and reducing agents for the synthesis of thermodynamically stable nanoparticles (NPs). Different types of nanotherapeutics have been synthesized using physical, chemical, and biological methods. Marine algae are a fascinating source of lead theranostics compounds, and the development of nanotheranostics has been linked to enhanced drug efficacy and safety. Indeed, algae are remarkable nanobiofactories, and their pragmatic properties reside in their (i) ease of handling; (ii) capacity to absorb/accumulate inorganic metallic ions; (iii) cost-effectiveness; and (iv) capacity of eco-friendly, rapid, and healthier synthesis of NPs. Preclinical and clinical trials shall enable to really define effective algal-based nanotherapies. This review aims to provide an overview of the main algal compounds that are nutraceuticals and that can be extracted and purified for nanotheranostic purposes.

Ecological and Industrial Implications of Dynamic Seaweed-Associated Microbiota Interactions.

Seaweeds are broadly distributed and represent an important source of secondary metabolites (e.g., halogenated compounds, polyphenols) eliciting various pharmacological activities and playing a relevant ecological role in the anti-epibiosis. Importantly, host (as known as basibiont such as algae)-microbe (as known as epibiont such as bacteria) interaction (as known as halobiont) is a driving force for coevolution in the marine environment. Nevertheless, halobionts may be fundamental (harmless) or detrimental (harmful) to the functioning of the host. In addition to biotic factors, abiotic factors (e.g., pH, salinity, temperature, nutrients) regulate halobionts. Spatiotemporal and functional exploration of such dynamic interactions appear crucial. Indeed, environmental stress in a constantly changing ocean may disturb complex mutualistic relations, through mechanisms involving host chemical defense strategies (e.g., secretion of secondary metabolites and antifouling chemicals by quorum sensing). It is worth mentioning that many of bioactive compounds, such as terpenoids, previously attributed to macroalgae are in fact produced or metabolized by their associated microorganisms (e.g., bacteria, fungi, viruses, parasites). Eventually, recent metagenomics analyses suggest that microbes may have acquired seaweed associated genes because of increased seaweed in diets. This article retrospectively reviews pertinent studies on the spatiotemporal and functional seaweed-associated microbiota interactions which can lead to the production of bioactive compounds with high antifouling, theranostic, and biotechnological potential.

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

INTRODUCTION: Trans-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 METHODS: Indeed, 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." RESULTS: With 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. CONCLUSION: In 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.

Synergistic Extraction of Europium (III) using Di-n-Butylsulfoxide and Picrolonic Acid.

AIM AND OBJECTIVE: Europium (Eu(III)) is a rare-earth metal, the softest, least dense, and most volatile member of lanthanides. It is greatly applied in the control rods of nuclear reactors. Although various extraction methods of Eu(III) have been reported, we present a novel mixture of easily available extractants in optimized experimental conditions to extract it efficiently, quickly, and cost-effectively. MATERIALS AND METHODS: Physical-chemical conditions (e.g., pH, equilibration time, temperature, europium concentration, extractants concentration, presence of specific metal ions) were optimized. The extractants, picrolonic acid (HPA) and di-n-butylsulfoxide (DBSO), were thoroughly mixed at equal concentration in chloroform. Standard Eu(III) solution was used for determining the method's accuracy. Reagent blank was prepared under identical conditions but without metal ions. Using the metallochromic dye arsenazo III as the blank, the absorbance of Eu(III) was measured spectrophotometrically at 651 nm. The distribution ratio (i.e., Eu(III) concentration in the aqueous phase before and after extraction) defined the extraction yield. RESULTS: HPA/DBSO mixture (0.01 M) had a synergistic effect on Eu(III) extraction (1.19×10-5 mole/dm3), achieving a maximum yield (≥ 99%) at pH 2, during 5 minutes equilibration at room temperature. Eu(III) extraction was reduced depending on the nature but not on the metal ions concentration. Extractants could be recycled four times without consequent degradation. Deionized water (dH2O) was the best strippant besides its availability and low-cost. The composition of the extracted adduct was defined as Eu(PA)3.2DBSO. CONCLUSION: This alternative method was found to be stable, simple, rapid, cost-effective, reliable, accurate and sensitive. It could be used for Eu(III) extraction and refining on a pilot plant scale.

Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?

Natural bioactive compounds with anti-carcinogenic activity are gaining tremendous interest in the field of oncology. Cinnamon, an aromatic condiment commonly used in tropical regions, appeared incredibly promising as an adjuvant for cancer therapy. Indeed, its whole or active parts (e.g., bark, leaf) exhibited significant anti-carcinogenic activity, which is mainly due to two cinnamaldehyde derivatives, namely 2-hydroxycinnaldehyde (HCA) and 2- benzoyloxycinnamaldehyde (BCA). In addition to their anti-cancer activity, HCA and BCA exert immunomodulatory, anti-platelets, and anti-inflammatory activities. The highly reactive α,ßunsaturated carbonyl pharmacophore, called Michael acceptor, contributes to their therapeutic effects. The molecular mechanisms underlying their anti-tumoral and anti-metastatic effects are miscellaneous, strongly suggesting that these compounds are multi-targeting compounds. Nevertheless, unravelling the exact molecular mechanisms of HCA and BCA remains a challenging matter which is necessary for optimal controlled-drug targeting delivery, safety, and efficiency. Eventually, their poor pharmacological properties (e.g., systemic bioavailability and solubility) represent a limitation and depend both on their administration route (e.g., per os, intravenously) and the nature of the formulation (e.g., free, smart nano-). This concise review focused on the potential of HCA and BCA as adjuvants in cancer. We describe their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.

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 underlying POAG 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.

Graphene, an Interesting Nanocarbon Allotrope for Biosensing Applications: Advances, Insights, and Prospects.

Graphene, a relatively new two-dimensional (2D) nanomaterial, possesses unique structure (e.g. lighter, harder, and more flexible than steel) and tunable physicochemical (e.g. electronical, optical) properties with potentially wide eco-friendly and cost-effective usage in biosensing. Furthermore, graphene-related nanomaterials (e.g. graphene oxide, doped graphene, carbon nanotubes) have inculcated tremendous interest among scientists and industrials for the development of innovative biosensing platforms, such as arrays, sequencers and other nanooptical/biophotonic sensing systems (e.g. FET, FRET, CRET, GERS). Indeed, combinatorial functionalization approaches are constantly improving the overall properties of graphene, such as its sensitivity, stability, specificity, selectivity, and response for potential bioanalytical applications. These include real-time multiplex detection, tracking, qualitative, and quantitative characterization of molecules (i.e. analytes [H2O2, urea, nitrite, ATP or NADH]; ions [Hg2+, Pb2+, or Cu2+]; biomolecules (DNA, iRNA, peptides, proteins, vitamins or glucose; disease biomarkers such as genetic alterations in BRCA1, p53) and cells (cancer cells, stem cells, bacteria, or viruses). However, there is still a paucity of comparative reports that critically evaluate the relative toxicity of carbon nanoallotropes in humans. This manuscript comprehensively reviews the biosensing applications of graphene and its derivatives (i.e. GO and rGO). Prospects and challenges are also introduced.

Development of Cephradine-Loaded Gelatin/Polyvinyl Alcohol Electrospun Nanofibers for Effective Diabetic Wound Healing: In-Vitro and In-Vivo Assessments.

Diabetic wound infections caused by conventional antibiotic-resistant Staphylococcus aureus strains are fast emerging, leading to life-threatening situations (e.g., high costs, morbidity, and mortality) associated with delayed healing and chronic inflammation. Electrospinning is one of the most widely used techniques for the fabrication of nanofibers (NFs), induced by a high voltage applied to a drug-loaded polymer solution. Particular attention is given to electrospun NFs for pharmaceutical applications (e.g., original drug delivery systems) and tissue regeneration (e.g., as tissue scaffolds). However, there is a paucity of reports related to their application in diabetic wound infections. Therefore, we prepared eco-friendly, biodegradable, low-immunogenic, and biocompatible gelatin (GEL)/polyvinyl alcohol (PVA) electrospun NFs (BNFs), in which we loaded the broad-spectrum antibiotic cephradine (Ceph). The resulting drug-loaded NFs (LNFs) were characterized physically using ultraviolet-visible (UV-Vis) spectrophotometry (for drug loading capacity (LC), drug encapsulation efficiency (EE), and drug release kinetics determination), thermogravimetric analysis (TGA) (for thermostability evaluation), scanning electron microscopy (SEM) (for surface morphology analysis), and Fourier-transform infrared spectroscopy (FTIR) (for functional group identification). LNFs were further characterized biologically by in-vitro assessment of their potency against S. aureus clinical strains (N = 16) using the Kirby-Bauer test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, by ex-vivo assessment to evaluate their cytotoxicity against primary human epidermal keratinocytes using MTT assay, and by in-vivo assessment to estimate their diabetic chronic wound-healing efficiency using NcZ10 diabetic/obese mice (N = 18). Thin and uniform NFs with a smooth surface and standard size (<400 nm) were observed by SEM at the optimized 5:5 (GEL:PVA) volumetric ratio. FTIR analyses confirmed the drug loading into BNFs. Compared to free Ceph, LNFs were significantly more thermostable and exhibited sustained/controlled Ceph release. LNFs also exerted a significantly stronger antibacterial activity both in-vitro and in-vivo. LNFs were significantly safer and more efficient for bacterial clearance-induced faster chronic wound healing. LNF-based therapy could be employed as a valuable dressing material to heal S. aureus-induced chronic wounds in diabetic subjects.

Green Synthesis of Ciprofloxacin-Loaded Cerium Oxide/Chitosan Nanocarrier and its Activity Against MRSA-Induced Mastitis.

Methicillin-resistant Staphylococcus aureus (MRSA)-induced mastitis is one of the biggest animal welfare issues and economic burdens worldwide. As a possible effective treatment, ciprofloxacin (CIP)-loaded cerium oxide (CeO2)/chitosan (CS) nanocomposite was synthesized using an eco-friendly approach, characterized, and evaluated. From 350 mastitis-positive milk samples, 35 mecA-positive MRSA strains were confirmed by antibiotic sensitivity testing and PCR. CeO2 nanoparticles (NPs) were synthetized using the seeds' extract of Amomum subulatum (aka black cardamom/BC) as a reducing and capping agent, which was conjugated with CS by ionic gelation before CIP was nanoencapsulated. The resulting NPs were characterized physically (by using FESEM, TEM, EDS, XRD, FTIR, ZP, and UV-Vis spectrophotometry), biologically and pharmacologically (through in-vitro/ex-vivo antibacterial, cytotoxic, and drug release behavior assays). The CIP-nanocomposite was represented by pure, stable, small, pseudospherical NPs of crystalline nature. FTIR confirmed the surface linkage of CS and CIP in CeO2 NPs. CIP-CeO2/CS nanocarrier exerted enhanced antibacterial activity at lower MIC (8 µg/mL) compared to that of free CIP drug alone. Also, they were hemocompatible and not hepatotoxic. CIP release from the nanocarrier was better sustained in physiological-like conditions. Taken together, the phytogenic CIP-CeO2/CS nanocarrier could be considered as a potent and safe therapeutic solution for MRSA-induced mastitis.

Breast Cancer Inhibition by Biosynthesized Titanium Dioxide Nanoparticles Is Comparable to Free Doxorubicin but Appeared Safer in BALB/c Mice.

Cancer remains a global health burden prompting affordable, target-oriented, and safe chemotherapeutic agents to reduce its incidence rate worldwide. In this study, a rapid, cost-effective, and green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) has been carried out; Ex vivo and in vivoevaluation of their safety and anti-tumor efficacy compared to doxorubicin (DOX), a highly efficient breast anti-cancer agent but limited by severe cardiotoxicity in many patients.Thereby,TiO2 NPs were eco-friendly synthetized using aqueous leaf extract of the tropical medicinal shrub Zanthoxylum armatum as a reducing agent. Butanol was used as a unique template. TiO2 NPs were physically characterized by ultraviolet-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) as routine state-of-the art techniques. The synthesized TiO2 NPs were then evaluated for their cytotoxicity (by MTT, FACS, and oxidative stress assays) in 4T1 breast tumor cells, and their hemocompatibility (by hemolysis assay). In vivo anti-tumor efficacy and safety of the TiO2 NPs were further assessed using subcutaneous 4T1 breast BALB/c mouse tumor model.The greenly prepared TiO2 NPs were small, spherical, and crystalline in nature. Interestingly, they were hemocompatible and elicited a strong DOX-like concentration-dependent cytotoxicity-induced apoptosis both ex vivo and in vivo (with a noticeable tumor volume reduction). The underlying molecular mechanism was, at least partially, mediated through reactive oxygen species (ROS) generation (lipid peroxidation). Unlike DOX (P < 0.05), it is important to mention that no cardiotoxicity or altered body weight were observed in both the TiO2 NPs-treated tumor-bearing mouse group and the PBS-treated mouse group (P > 0.05). Taken together, Z. armatum-derived TiO2 NPs are cost-effective, more efficient, and safer than DOX. The present findings shall prompt clinical trials using green TiO2 NPs, at least as a possible alternative modality to DOX for effective breast cancer therapy.

Green and Cost-Effective Synthesis of Metallic Nanoparticles by Algae: Safe Methods for Translational Medicine.

Metal nanoparticles (NPs) have received much attention for potential applications in medicine (mainly in oncology, radiology and infectiology), due to their intriguing chemical, electronical, catalytical, and optical properties such as surface plasmon resonance (SPR) effect. They also offer ease in controlled synthesis and surface modification (e.g., tailored properties conferred by capping/protecting agents including N-, P-, COOH-, SH-containing molecules and polymers such as thiol, disulfide, ammonium, amine, and multidentate carboxylate), which allows (i) tuning their size and shape (e.g., star-shaped and/or branched) (ii) improving their stability, monodispersity, chemical miscibility, and activity, (iii) avoiding their aggregation and oxidation over time, (iv) increasing their yield and purity. The bottom-up approach, where the metal ions are reduced in the NPs grown in the presence of capping ligands, has been widely used compared to the top-down approach. Besides the physical and chemical synthesis methods, the biological method is gaining much consideration. Indeed, several drawbacks have been reported for the synthesis of NPs via physical (e.g., irradiation, ultrasonication) and chemical (e.g., electrochemisty, reduction by chemicals such as trisodium citrate or ascorbic acid) methods (e.g., cost, and/ortoxicity due to use of hazardous solvents, low production rate, use of huge amount of energy). However, (organic or inorganic) eco-friendly NPs synthesis exhibits a sustainable, safe, and economical solution. Thereby, a relatively new trend for fast and valuable NPs synthesis from (live or dead) algae (i.e., microalgae, macroalgae and cyanobacteria) has been observed, especially because of its massive presence on the Earth's crust and their unique properties (e.g., capacity to accumulate and reduce metallic ions, fast propagation). This article discusses the algal-mediated synthesis methods (either intracellularly or extracellularly) of inorganic NPs with special emphasis on the noblest metals, i.e., silver (Ag)- and gold (Au)-derived NPs. The key factors (e.g., pH, temperature, reaction time) that affect their biosynthesis process, stability, size, and shape are highlighted. Eventually, underlying molecular mechanisms, nanotoxicity and examples of major biomedical applications of these algal-derived NPs are presented.

Fabrication, physical characterizations and in vitro antibacterial activity of cefadroxil-loaded chitosan/poly(vinyl alcohol) nanofibers against Staphylococcus aureus clinical isolates.

Particular attention is devoting to the design of electrospun nanofibers (NFs) as new drug delivery nanosystems to overcome bacterial resistance and toxicological issues. Their advantages include high encapsulation efficiency, great drug-loading capacity, easiness in production, cost-effectiveness, and controlled targeted drug delivery. We aim to characterize electrospun chitosan (CS)/poly(vinyl alcohol) (PVA) NFs (CPNFs) loaded with cefadroxil monohydrate (CFX), a broad spectrum antibiotic. The biodegradable and biocompatible carrier system was greenly fabricated by electrospinning at various CS/PVA ratios. CPNFs were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and UV-spectrometry. Their potential toxicity was evaluated in human epidermal keratinocytes by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Their antibacterial activity was tested by agar well diffusion method and MTT assay against clinical isolates of Staphylococcus aureus, a Gram-positive bacterium involved in serious skin infections. The thermostable CFX-loaded CPNFs at optimized 30:70 ratio revealed a burst and sustained release profile that occurred predominantly by diffusion following non-Fickian (anomalous) transport mechanism, as well as a more potent and safe antibacterial than free CFX. Thus, electrospun CFX-loaded CPNFs could be a new promising transdermal drug delivery system to activate the wound healing process and cost-effectively treat S. aureus-induced (resistant) skin infections.

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.

Favourable influence of hydrophobic surfaces on protein structure in porous organically-modified silica glasses.

Organically-modified siloxanes were used as host materials to examine the influence of surface chemistry on protein conformation in a crowded environment. The sol-gel materials were prepared from tetramethoxysilane and a series of monosubstituted alkoxysilanes, RSi(OR')(3), featuring alkyl groups of increasing chain length in the R-position. Using circular dichroism spectroscopy in the far-UV region, apomyoglobin was found to transit from an unfolded state to a native-like helical state as the content of the hydrophobic precursor increased from 0 to 15%. At a fixed molar content of 5% RSi(OR')(3), the helical structure of apomyoglobin increased with the chain length of the R-group, i.e. methyl

Isolation, purification, structural elucidation and antimicrobial activities of kocumarin, a novel antibiotic isolated from actinobacterium Kocuria marina CMG S2 associated with the brown seaweed Pelvetia canaliculata.

AIMS: Screening of seaweed-associated bacteria capable of producing antimicrobials. METHODS AND RESULTS: Fifteen microbial strains, associated to the brown seaweed Pelvetia canaliculata (Linnaeus) attached to the rocks of Sonmiani Beach (Karachi, Pakistan), were screened. Crude extract filtrates of CMG S2 strain grew on Zobell marine agar (ZMA) had the most remarkable antimicrobial activity. Based on its phenotypic aspects (e.g. Gram-positive, microccoid form), biochemical characteristics (e.g. halotolerance) and genetic analyses, CMG S2 is identified as a putatively new Kocuria marina type strain belonging to the actinobacteria's class and micrococcaceae family. Thereby, the nucleotide sequence analysis of its full-length 16S ribosomal ribonucleic acid (rRNA) gene (GenBank accession number EU073966.1) displayed highest identity (i.e. 99%) and score (2630) with K. marina KMM 3905. Phylogenic trees analysis using the neighbor-joining method showed closest evolutionary distance of CMG S2 with KMM 3905 strain and K. carniphila (DC2201) specie. Interestingly, a unique ultraviolet (UV)-bioactive compound was purified from CMG S2 crude extracts by flash silica gel column and thin-layer chromatography (TLC) techniques. Its chemical structure was unraveled as 4-[(Z)-2 phenyl ethenyl] benzoic acid (PEBA, later named kocumarin) by nuclear magnetic resonance (NMR) spectroscopy techniques. Importantly, kocumarin demonstrated prominent and rapid growth inhibition against all tested fungi and pathogenic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), with a minimal fungal inhibitory concentration (MFC) of 15-25µg/mL and a minimal (bacterial) inhibitory concentration (MIC) of 10-15µg/mL. SIGNIFICANCE AND IMPACT OF THE STUDY: Kocumarin represents a new promising natural antibiotic for in vivo and environmental applications.

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.

Spectro-Fluor™ Technology for Reliable Detection of Proteins and Biomarkers of Disease: A Pioneered Research Study.

Quantitative and qualitative characterization of fluorinated molecules represents an important task. Fluorine-based medicinal chemistry is a fast-growing research area due to the positive impact of fluorine in drug discovery, and clinical and molecular imaging (e.g., magnetic resonance imaging, positron emission tomography). Common detection methods include fluorinated-based labelling using radioactive isotopes or fluorescent dyes. Nevertheless, these molecular imaging methods can be harmful for health due to the potential instability of fluorochromes and cytoxicity of radioisotopes. Therefore, these methods often require expensive precautionary measures. In this context, we have developed, validated and patented carbon-fluorine spectroscopy (CFS™), recently renamed Spectro-Fluor™ technology, which among a non-competitive family of in-house made devices called PLIRFA™ (Pulsed Laser Isochronic Raman and Fluorescence Apparatus™), allows reliable detection of Carbon-Fluorine (C-F) bonds. C-F bonds are known to be stable and safe labels once incorporated to any type of molecules, cells, compounds or (nano-) materials. In this pioneered research study, we used Spectro-Fluor™ to assess biomarkers. As a proof-of-principle experiment, we have established a three-step protocol intended to rapid protein detection, which simply consisted of: (i) incorporating a sufficient concentration of an aromatic amino-acid (fluorinated versus non-fluorinated) into cultured cells; (ii) simultaneously isolating the fluorinated protein of interest and the non-fluorinated form of the protein (control) by immune-precipitation; (iii) comparatively analyzing the respective spectrum obtained for the two protein forms by Spectro-Fluor™. Thereby, we were able to differentiate, from colon cancer cells HCT-116, the fluorinated and non-fluorinated forms of p21, a key transcriptional factor and downstream target of p53, the so-called "guardian of the genome". Taken together, our data again demonstrates the beneficial alternative use of Spectro-Fluor™, which once combined with an innovative methodology permits one to quickly, reliably, safely and cost-effectively detect physiological or pathological proteins in cells.

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.

A study of pH effects on the bacterial surface physicochemical properties of Acinetobacter baumannii.

The first step in the biofilm formation is the bacterial attachment to solid surfaces, which is dependent on the bacteria cell surface physico-chemical properties. The purpose of this work was to analyze the effect of pH on the physicochemical cell surface properties of Acinetobacter baumannii by two different methods. The cell surface properties were evaluated using the microbial adhesion to solvents method (MATS) and contact angle measurements (CAM). MATS technique allowed us to enlighten that A. baumannii was hydrophilic at the different values of pH. It was found that at a desired pH of 6.5, the strain presents a maximum and stable value of electron-donor characteristic, while the electron acceptor character increased as the pH increased. Regardless of the methods employed, the obtained results using MATS and CAM confirmed the influence of the pH on the surface physicochemical properties of A. baumannii. The cell surface electron-donor and electron-acceptor character at pH 6.5 was found to be quite similar using both methods.

Characterization of bacterial biofilms formed on urinary catheters.

BACKGROUND: The formation of bacterial biofilms on urinary catheters is a leading cause of urinary tract infections in intensive care units. Cytobacteriological examination of urine from patients is often misleading, due to the formation of these biofilms. Therefore, characterizing these biofilms and identifying the bacterial species residing on the surface of catheters are of major importance. METHODS: We studied the formation of biofilms on the inner surface of urinary catheters using microbiological culture techniques, with the direct contact of catheter pieces with blood agar. The bacterial species on the surface were characterized by scanning electron microscopy, and the kinetic profile of biofilm formation on a silicone substrate for an imipenem-resistant Acinetobacter baumannii bacterium was evaluated with a crystal violet staining assay. RESULTS: The bacterial species that constituted these biofilms were identified as a variety of gram-negative bacilli, with a predominance of strains belonging to Pseudomonas aeruginosa. The other isolated strains belonged to A baumannii and Klebsiella ornithinolytica. Kinetic profiling of biofilm formation identified the transient behavior of A baumannii between its biofilm and planktonic state. This strain was highly resistant to all of the antibiotics tested except colistin. Scanning electron microscopy images showed that the identified isolated species formed a dense and interconnected network of cellular multilayers formed from either a single cell or from different species that were surrounded and enveloped by a protective matrix. CONCLUSIONS: Microbiological analysis of the intraluminal surface of the catheter is required for true identification of the causative agents of catheter-associated urinary tract infections. This approach, combined with a routine cytobacteriological examination of urine, allows for the complete characterization of biofilm-associated species, and also may help prevent biofilm formation in such devices and help guide optimum antibiotic treatment.