Insights into phenolic compounds from microalgae: structural variety and complex beneficial activities from health to nutraceutics.

Phenolic compounds (PCs) are a family of secondary metabolites with recognized biological activities making them attractive for the biomedical "red" biotechnology. The development of the eco-sustainable production of natural bioactive metabolites requires using easy cultivable organisms, such as microalgae, which represents one of the most promising sources for biotechnological applications. Microalgae are photosynthetic organisms inhabiting aquatic systems, displaying high levels of biological and functional diversities, and are well-known producers of fatty acids and carotenoids. They are also rich in other families of bioactive molecules e.g. phenolic compounds. Microalgal PCs however are less investigated than other molecular components. This study aims to provide a state-of-art picture of the actual knowledge on microalgal phenolic compounds, reviewing information on the PC content variety and chemodiversity in microalgae, their environmental modulation, and we aim to report discuss data on PC biosynthetic pathways. We report the challenges of promoting microalgae as a relevant source of natural PCs, further enhancing the interests of microalgal "biofactories" for biotechnological applications (i.e. nutraceutical, pharmacological, or cosmeceutical products).

DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease.

Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1-6 ANN NEUROL 2019;85:296-301.

Challenging microalgal vitamins for human health.

BACKGROUND: Vitamins' deficiency in humans is an important threat worldwide and requires solutions. In the concept of natural biofactory for bioactive compounds production, microalgae represent one of the most promising targets filling many biotechnological applications, and allowing the development of an eco-sustainable production of natural bioactive metabolites. Vitamins are probably one of the cutting edges of microalgal diversity compounds. MAIN TEXT: Microalgae can usefully provide many of the required vitamins in humans, more than terrestrial plants, for instance. Indeed, vitamins D and K, little present in many plants or fruits, are instead available from microalgae. The same occurs for some vitamins B (B12, B9, B6), while the other vitamins (A, C, D, E) are also provided by microalgae. This large panel of vitamins diversity in microalgal cells represents an exploitable platform in order to use them as natural vitamins' producers for human consumption. This study aims to provide an integrative overview on vitamins content in the microalgal realm, and discuss on the great potential of microalgae as sources of different forms of vitamins to be included as functional ingredients in food or nutraceuticals for the human health. We report on the biological roles of vitamins in microalgae, the current knowledge on their modulation by environmental or biological forcing and on the biological activity of the different vitamins in human metabolism and health protection. CONCLUSION: Finally, we critically discuss the challenges for promoting microalgae as a relevant source of vitamins, further enhancing the interests of microalgal "biofactory" for biotechnological applications, such as in nutraceuticals or cosmeceuticals.

Nutrient removal efficiency of green algal strains at high phosphate concentrations.

The effects of autotrophic and mixotrophic conditions on microalgae growth and nutrient removal efficiency from synthetic wastewater by different microalgae were investigated. Although several studies have demonstrated the suitability of microalgae technologies for ammonia-rich wastewater treatment, only a few have been used for treatment of phosphate-rich industrial wastewaters. In this work, six microalgae were cultivated in batch mode in a growth medium with a high phosphate concentration (0.74 Mm PO4 3--P) and different carbon sources (ammonium acetate and sodium bicarbonate) without CO2 supplementation or pH adjustment. Their potential for nutrient removal and biomass generation was estimated. The biomass growth in the reactors was modeled and the data aligned to the Verhulst model with R2 > 0.93 in all cases. Chlorella pyrenoidosa ACUF_808 showed the highest final biomass productivity of 106.21 and 75.71 mg·L-1·d-1 in media with inorganic and organic carbon sources, respectively. The highest phosphorus removal efficiency was 32% with Chlorella vulgaris ACUF_809, while the nitrate removal efficiency in all reactors exceeded 93%. The coupled cultivation of the novel isolated strains of C. pyrenoidosa and C. vulgaris under mixotrophic conditions supplemented with ammonium acetate might be a promising solution for simultaneous nitrate and phosphate removal from phosphorus-rich wastewaters.

On the human health benefits of microalgal phytohormones: An explorative in silico analysis.

Phytohormones represent a group of secondary metabolites with different chemical structures, in which belong auxins, cytokinins, gibberellins, or brassinosteroids. In higher plants, they cover active roles in growth or defense function, while their potential benefits for human health protection were noted for some phytohormones and little explored for many others. In this study, we developed a target fishing strategy on fifty-three selected naturally occurring phytohormones covering different families towards proteins involved in key cellular functions related to human metabolism and health protection/disease. This in silico analysis strategy aims to screen the potential human health-driven bioactivity of more than fifty phytohormones through the analysis of their interactions with specific targets. From this analysis, twenty-eight human targets were recovered. Some targets e.g., the proteins mitochondrial glutamate dehydrogenase (GLUD1) or nerve growth factor (NGF) bound many phytohormones, highlighting their involvement in amino acid metabolism and/or in the maintenance or survival of neurons. Conversely, some phytohormones specifically interacted with some proteins, e.g., SPRY domain-containing SOCS box protein 2 (SPSB2) or Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1), both involved in human immune response. They were then investigated with a molecular docking analysis approach. Our bioprospecting study indicated that many phytohormones may endow human health benefits, with potential functional role in multiple cellular processes including immune response and cell cycle progression.

Biotechnological response curve of the cyanobacterium Spirulina subsalsa to light energy gradient.

BACKGROUND: Microalgae represent a suitable and eco-sustainable resource for human needs thanks to their fast growth ability, together with the great diversity in species and intracellular secondary bioactive metabolites. These high-added-value compounds are of great interest for human health or animal feed. The intracellular content of these valuable compound families is tightly associated with the microalgal biological state and responds to environmental cues, e.g., light. Our study develops a Biotechnological response curve strategy exploring the bioactive metabolites synthesis in the marine cyanobacterium Spirulina subsalsa over a light energy gradient. The Relative Light energy index generated in our study integrates the red, green and blue photon flux density with their relative photon energy. The Biotechnological response curve combined biochemical analysis of the macromolecular composition (total protein, lipid, and carbohydrate content), total sterols, polyphenols and flavonoids, carotenoids, phenolic compounds, vitamins (A, B1, B2, B6, B9, B12, C, D2, D3, E, H, and K1), phycobiliproteins, together with the antioxidant activity of the biomass as well as the growth ability and photosynthesis. RESULTS: Results demonstrated that light energy significantly modulate the biochemical status of the microalga Spirulina subsalsa revealing the relevance of the light energy index to explain the light-induced biological variability. The sharp decrease of the photosynthetic rate at high light energy was accompanied with an increase of the antioxidant network response, such as carotenoids, total polyphenols, and the antioxidant capacity. Conversely, low light energy favorized the intracellular content of lipids and vitamins (B2, B6, B9, D3, K1, A, C, H, and B12) compared to high light energy. CONCLUSIONS: Results of the Biotechnological response curves were discussed in their functional and physiological relevance as well as for the essence of their potential biotechnological applications. This study emphasized the light energy as a relevant tool to explain the biological responses of microalgae towards light climate variability, and, therefore, to design metabolic manipulation of microalgae.

The Carotenoid Diatoxanthin Modulates Inflammatory and Angiogenesis Pathways In Vitro in Prostate Cancer Cells.

Xanthophylls, a group of carotenoids, have attracted attention as human health benefit compounds thanks to their functionality and bioavailability. The great antioxidant and anti-inflammatory abilities of diatoxanthin (Dt), a photoprotective xanthophyll synthetized by diatoms, were recently documented. This study investigates the capacity of Dt to intercept prostate cancer progression in vitro on different human cell lines, exploring its role against cancer proliferation and angiogenesis. Our results highlighted the chemopreventive role of Dt already at low concentration (44.1 pM) and suggest that the Dt-induced cancer cell death occurred through oxidative stress mechanisms. This hypothesis was supported by variations on the expression of key genes and proteins. Oxidative stress cell deaths (e.g., ferroptosis) are recently described types of cell death that are closely related to the pathophysiological processes of many diseases, such as tumors. Nonetheless, the interest of Dt was further strengthened by its ability to inhibit angiogenesis. The results are discussed considering the actual progress and requirements in cancer therapy, notably for prostate cancer.

Insights into the biosynthesis pathway of phenolic compounds in microalgae.

Among the most relevant bioactive molecules family, phenolic compounds (PCs) are well known in higher plants, while their knowledge in microalgae is still scarce. Microalgae represent a novel and promising source of human health benefit compounds to be involved, for instance, in nutraceutical composition. This study aims to investigate the PCs biosynthetic pathway in the microalgal realm, exploring its potential variability over the microalgal biodiversity axis. A multistep in silico analysis was carried out using a selection of core enzymes from the pathway described in land plants. This study explores their presence in ten groups of prokaryotic and eukaryotic microalgae.. Analyses were carried out taking into account a wide selection of algal protein homologs, functional annotation of conserved domains and motifs, and maximum-likelihood tree construction. Results showed that a conserved core of the pathway for PCs biosynthesis is shared horizontally in all microalgae. Conversely, the ability to synthesize some subclasses of phenolics may be restricted to only some microalgal groups (i.e., Chlorophyta) depending on featured enzymes, such as the flavanone naringenin and other related chalcone isomerase dependent compounds.

A Comparative Analysis of Mucus Immunomodulatory Properties from Seven Marine Gastropods from the Mediterranean Sea.

The treatment of inflammatory and immune-related diseases due to dysfunctioning of the immune system necessitates modulation of the immune response through immunomodulatory compounds. Marine environments are considered as a new frontier for health benefit product implementations. Marine biodiversity is still a low explored resource, despite it is expected to represent an important platform for chemical bioactive compounds. Within the phylum Mollusca, gastropods are known to synthetize mucus, the latter presenting relevant bioactive properties, e.g., related to immunomodulant molecules able to activate the innate and acquired immune system. This study proposes a bioprospecting of the immunomodulant activity of mucus isolated from seven common gastropod species from the Gulf of Naples (Mediterranean Sea). Results showed that not all mucus displayed a significant cytotoxic activity on the two human cancer cell lines A549 and A2058. On the other hand, the mucus from Bolinus brandaris was strongly bioactive and was therefore thoroughly investigated at cellular, molecular, and protein levels on the human monocytes U937 line. It can conclusively induce monocyte differentiation in vitro and significantly stimulate natural immunity response.

The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells.

Contact between SARS-CoV-2 and human lung cells involves the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, the latter being strongly involved in the regulation of inflammation as well as blood pressure homeostasis. SARS-CoV-2 infection is characterized by a strong inflammatory response defined as a "cytokine storm". Among recent therapeutic approaches against SARS-CoV-2 targeting the dramatic inflammatory reaction, some natural products are promising. Diatoms are microalgae able to produce bioactive secondary metabolites, such as the xanthophyll diatoxanthin (Dt). The aim of this study is to demonstrate the anti-inflammatory effects of Dt on the A549-hACE2 lung cell line, exploring its interaction with the ACE2 receptor, as well as depicting its role in inhibiting a cytokine storm induced by the SARS-CoV-2 spike glycoprotein. Results showed that Dt enhanced the cell metabolism, e.g., the percent of metabolically active cells, as well as the ACE2 enzymatic activity. Moreover, Dt strongly affected the response of the SARS-CoV-2 spike glycoprotein-exposed A549-hACE2 cells in decreasing the interleukin-6 production and increasing the interleukin-10 release. Moreover, Dt upregulated genes encoding for the interferon pathway related to antiviral defense and enhanced proteins belonging to the innate immunity response. The potential interest of Dt as a new therapeutic agent in the treatment and/or prevention of the severe inflammatory syndrome related to SARS-CoV-2 infection is postulated.

Microbial biofilm community structure and composition on the lithic substrates of Herculaneum Suburban Baths.

In this work, we want to investigate the impact of different substrates and different environmental condition on the biofilm communities growing on plaster, marble, and mortar substrates inside the Herculaneum Suburban Baths. To do so, we measured environmental conditions and sampled biofilm communities along the walls of the baths and used culture-dependent and -independent molecular techniques (DGGE) to identify the species at each sampling sites. We used the species pool to infer structure and richness of communities within each site in each substrate, and confocal light scanning microscopy to assess the three-dimensional structure of the sampled biofilms. To gather further insights, we built a meta-community network and used its local realizations to analyze co-occurrence patterns of species. We found that light is a limiting factor in the baths environment, that moving along sites equals moving along an irradiation gradient, and that such gradient shapes the community structure, de facto separating a dark community, rich in Bacteria, Fungi and cyanobacteria, from two dim communities, rich in Chlorophyta. Almost all sites are dominated by photoautotrophs, with Fungi and Bacteria relegated to the role of rare species., and structural properties of biofilms are not consistent within the same substrate. We conclude that the Herculaneum suburban baths are an environment-shaped community, where one dark community (plaster) and one dim community (mortar) provides species to a "midway" community (marble).

A Spotlight on Rad52 in Cyanidiophytina (Rhodophyta): A Relic in Algal Heritage.

The RADiation sensitive52 (RAD52) protein catalyzes the pairing between two homologous DNA sequences' double-strand break repair and meiotic recombination, mediating RAD51 loading onto single-stranded DNA ends, and initiating homologous recombination and catalyzing DNA annealing. This article reports the characterization of RAD52 homologs in the thermo-acidophilic Cyanidiophyceae whose genomes have undergone extensive sequencing. Database mining, phylogenetic inference, prediction of protein structure and evaluation of gene expression were performed in order to determine the functionality of the RAD52 protein in Cyanidiophyceae. Its current function in Cyanidiophytina could be related to stress damage response for thriving in hot and acidic environments as well as to the genetic variability of these algae, in which, conversely to extant Rhodophyta, sexual mating was never observed.

Biofilm architecture on different substrates of an Oculatella subterranea (Cyanobacteria) strain isolated from Pompeii archaeological site (Italy).

The Cyanobacterium Oculatella subterranea Zammit, Billi, Albertano inhabits hypogea and stone caves and is a pioneer of different stone substrata. In this study, a strain isolated from the House of Marco Castricio (Archaeological Park of Pompeii, Italy) was identified by a polyphasic approach and used for an in vitro colonization test to verify the influence of the substrate on the biofilm architecture. Fine structure of O. subterranea microbial mats was revealed as well as filaments orientation toward light source. This aim has been achieved through confocal laser scanner microscope microscopy and computer image analysis. Moreover, bioreceptivity of five different substrates, commonly retrieved in archaeological sites of Campania, was assessed for O. subterranea. Our results show that the three-dimensional structure of O. subterranea microbial mats is poorly affected by physical and geochemical features of substrates: in fact, the porous architecture of its biofilm was preserved, independently of the materials. On the other hand, the area/perimeter ratio relative to the O. subterranea growth on tuff, brick, and porphyry showed significant differences, indicating dissimilar levels of bioreceptivity of the three substrates.