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In the last decades Blue Growth policy in european and non-european countries produced a great impulse in applied marine sciences, comprehending the research of new bioactive molecules in marine organisms. These organisms are a great source of natural compounds with unique features resulting from the huge variability of marine habitats and species living in them. Most of the marine compounds in use and in clinical trials are drugs for cancer therapy and many of them are conjugated to antibody to form antibody-drug conjugates (ADCs). Severe pain, viral infections, hypertriglyceridemia, obesity, Alzheimer’s and other CNS diseases are further target conditions for these pharmaceuticals. This review summarizes the state-of-the-art marine drugs focusing on the most successful results in the fast expanding field of marine pharmacology.

Diet has a strong influence on many physiological processes, which in turn have important implications on a variety of pathological conditions. In this respect, microRNAs (miRNAs), a class of small non-coding RNAs playing a relevant epigenetic role in controlling gene expression, may represent mediators between the dietary intake and the healthy status. Despite great advances in the field of nutri-epigenomics, it remains unclear how miRNA expression is modulated by the diet and, specifically, the intake of specific nutrients. We investigated the whole circulating miRNome by small RNA-sequencing performed on plasma samples of 120 healthy volunteers with different dietary habits (vegans, vegetarians, and omnivores). Dietary intakes of specific nutrients were estimated for each subject from the information reported in the food-frequency questionnaire previously validated in the EPIC study. We focused hereby on the intake of 23 natural compounds (NCs) of the classes of lipids, micro-elements, and vitamins. We identified 78 significant correlations (rho > 0.300, p -value < 0.05) among the estimated daily intake of 13 NCs and the expression levels of 58 plasma miRNAs. Overall, vitamin D, sodium, and vitamin E correlated with the largest number of miRNAs. All the identified correlations were consistent among the three dietary groups and 22 of them were confirmed as significant ( p -value < 0.05) by age-, gender-, and body-mass index-adjusted Generalized Linear regression Model analysis. miR-23a-3p expression levels were related with different NCs including a significant positive correlation with sodium (rho = 0.377) and significant negative correlations with lipid-related NCs and vitamin E. Conversely, the estimated intake of vitamin D was negatively correlated with the expression of the highest number of circulating miRNAs, particularly miR-1277-5p (rho = −0.393) and miR-144-3p (rho = −0.393). Functional analysis of the targets of sodium intake-correlated miRNAs highlighted terms related to cardiac development. A similar approach on targets of those miRNAs correlated with vitamin D intake showed an enrichment in genes involved in hormone metabolisms, while the response to chronic inflammation was among the top enriched processes involving targets of miRNAs negatively related with vitamin E intake. Our findings show that nutrients through the habitual diet influence circulating miRNA profiles and highlight that this aspect must be considered in the nutri-epigenomic research.

Arthrospira platensis holds promise for biotechnological applications due to its rapid growth and ability to produce valuable bioactive compounds like phycocyanin (PC). This study explores the impact of salinity and brewery wastewater (BWW) on the mixotrophic cultivation of A. platensis. Utilizing BWW as an organic carbon source and seawater (SW) for salt stress, we aim to optimize PC production and biomass composition. Under mixotrophic conditions with 2% BWW and SW, A. platensis showed enhanced biomass productivity, reaching a maximum of 3.70 g L−1 and significant increases in PC concentration. This study also observed changes in biochemical composition, with elevated protein and carbohydrate levels under salt stress that mimics the use of seawater. Mixotrophic cultivation with BWW and SW also influenced the FAME profile, enhancing the content of C16:0 and C18:1 FAMES. The purity (EP of 1.15) and yield (100 mg g−1) of PC were notably higher in mixotrophic cultures, indicating the potential for commercial applications in food, cosmetics, and pharmaceuticals. This research underscores the benefits of integrating the use of saline water with waste valorization in microalgae cultivation, promoting sustainability and economic efficiency in biotechnological processes.

Octocorals have proven to be a prolific source of bioactive natural products, exhibiting a wide spectrum of pharmacological activities. Among octocorals, Pennatulaceans, commonly known as sea pens, are among the most dominant soft coral species living in benthic communities. Nonetheless, reports on bioactivity and chemical investigations of this genus are scarce. This prompted us to shed light on the pharmacological potential of the extracts of the sea pen Pennatula phosphorea, Linneus 1758, and gain an overview of its metabolome. Crude octocoral extracts, obtained with a modified Kupchan extraction protocol, were assessed for their bioactivity potential, revealing the hexanic extract to exert anti-inflammatory effects and interesting protective properties in an in vitro model of sarcopenia and in auditory HEI-OC1 cisplatin-treated cells, while the chloroformic extract was active in reducing A375 melanoma cell viability in a concentration-dependent manner. An untargeted metabolomic analysis unveiled that P. phosphorea collects a wide array of glycerophospholipids and phosphosphingolipids belonging to the ceramide phosphoinositol class, which were exclusive or more abundant in the hexanic extract. Their proven anti-inflammatory and cytoprotective effects could demonstrate the activity shown by the P. phosphorea hexanic extract. In addition, a group of prostaglandins, eluted mainly in the chloroformic extract, were putatively annotated. Since prostanoids from marine origin have been demonstrated to exert cytotoxic and anti-proliferative properties against various cancer cell lines, the presence of PGs in the P. phosphorea chloroform extract could justify its anti-melanoma activity. This is the first report on the presence of glycerophospholipids, phosphosphingolipids, and prostaglandins, along with the identification of novel congeners, in sea pens.

Apigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity. Male C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations. When compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens. Apigenin prevents systemic metabolic alterations, counteracts enteric inflammation and normalizes colonic dysmotility associated with obesity.

Extra-virgin olive oil (EVOO) polyphenols contribute to Mediterranean diet health-promoting properties. One of the most abundant secoiridoid present in EVOO, Oleacein (OA), demonstrated anticancer activity against several tumors. Nevertheless, its role against melanoma has not still investigated. This study aimed at determining in vitro the antimelanoma activity of OA and the relative mechanism of action. OA induced cell growth inhibition in 501Mel melanoma cells with an IC50 in the low micromolar range of concentrations. Moreover, an OA concentration approximating the IC50 induced G1/S phase arrest, DNA fragmentation, and downregulation of genes encoding antiapoptotic (BCL2 and MCL1) and proproliferative (c-KIT, K-RAS, PIK3R3, mTOR) proteins, while increased transcription levels of the proapoptotic protein BAX. Concordantly, OA increased the levels of miR-193a-3p (targeting MCL1, c-KIT and K-RAS), miR-193a-5p (targeting PIK3R3 and mTOR), miR-34a-5p (targeting BCL2 and c-KIT) and miR-16-5p (miR-16-5p targeting BCL2, K-RAS and mTOR), while decreased miR-214-3p (targeting BAX). These modulatory effects might contribute to the inhibition of 501Mel melanoma cell growth observed after treatment with an olive leaves-derived formulation rich in OA, with potential application against in situ cutaneous melanoma. Altogether, these results demonstrate the ability of OA to contrast the proliferation of cutaneous melanoma cells through the transcriptional modulation of relevant genes and microRNAs, confirming the anticancer potential of EVOO and suggesting OA as a chemopreventive agent for cancer disease therapy.

Hearing loss is one of the most common sensory disorders in humans, and a large number of cases are due to ear cell damage caused by ototoxic drugs including anticancer agents, such as cisplatin. The recent literature reported that hearing loss is promoted by an excessive generation of reactive oxygen species (ROS) in cochlea cells, which causes oxidative stress. Recently, polysaccharides from the cyanobacterium Arthrospira platensis showed many biological activities, including antioxidant activity, suggesting their potential use to combat hearing loss. On these bases, this study describes the extraction, purification, and characterization of water-soluble polysaccharides from A. platensis (SPPs) and the investigation of their protective role against cisplatin toxicity on House Ear Institute-Organ of Corti (HEI-OC1) cells. The results showed that SPPs (5–80 µg/mL) induced a dose-dependent increase in viability, statistically significant at 40 µg/mL and 80 µg/mL. Moreover, SPPs, evaluated at 80 µg/mL, inhibited the cisplatin-induced ROS level increase in HEI-OC1. This evidence highlights the potential of SPPs as natural candidates to protect cochlear ear cells against ototoxic oxidative agents. Moreover, in view of the potential use of microalgal polysaccharides to realize hydrogels, SPPs could also represent a healthy carrier for other topically administered otoprotective agents.

The natural environment represents an important source of drugs that originates from the terrestrial and, in minority, marine organisms. Indeed, the marine environment represents a largely untapped source in the process of drug discovery. Among all marine organisms, sponges with algae represent the richest source of compounds showing anticancer activity. In this study, the two secondary metabolites pelorol (PEL) and 5-epi-ilimaquinone (EPI), purified from Dactylospongia elegans were investigated for their anti-melanoma activity. PEL and EPI induced cell growth repression of 501Mel melanoma cells in a concentration- and time-dependent manner. A cell cycle block in the G1 phase by PEL and EPI was also observed. Furthermore, PEL and EPI induced significant accumulation of DNA histone fragments in the cytoplasmic fraction, indicating a pro-apoptotic effect of both compounds. At the molecular level, PEL and EPI induced apoptosis through the increase in pro-apoptotic BAX expression, confirmed by the decrease in its silencing miR-214-3p and the decrease in the anti-apoptotic BCL-2, MCL1, and BIRC-5 mRNA expression, attested by the increase in their silencing miRNAs, i.e., miR-193a-3p and miR-16-5p. In conclusion, our data indicate that PEL and EPI exert cytotoxicity activity against 501Mel melanoma cells promoting apoptotic signaling and inducing changes in miRNA expression and their downstream effectors. For these reasons could represent promising lead compounds in the anti-melanoma drug research.

For topical treatment of skin cancer, the design of pH-responsive nanocarriers able to selectively release the drug in the tumor acidic microenvironment represents a reliable option for targeted delivery. In this context, a series of newly synthesized surface-active fatty acid-protic ionic liquids (FA-PILs), based on tetramethylguanidinium cation and different natural hydrophobic fatty acid carboxylates, have been investigated with the aim of developing a pH-sensitive nanostructured drug delivery system for cutaneous administration in the skin cancer therapy. The capability of FA-PILs to arrange in micelles when combined with each other and with the non-ionic surfactant d-α-Tocopherol polyethylene glycol succinate (vitamin E TPGS) as well as their ability to solubilize imiquimod, an immuno-stimulant drug used for the treatment of skin cancerous lesions, have been demonstrated. The FA-PILs-TPGS mixed micelles showed pH-sensitivity, suggesting that the acidic environment of cancer cells can trigger nanostructures’ swelling and collapse with consequent rapid release of imiquimod and drug cytotoxic potential enhancement. The in vitro permeation/penetration study showed that the micellar formulation produced effective imiquimod concentrations into the skin exposed to acid environment, representing a potential efficacious and selective drug delivery system able to trigger the drug release in the tumor tissues, at lower and less irritating drug concentrations.

This study explores the mixotrophic cultivation of Limnospira platensis using dairy byproducts, specifically scotta whey (SW), buttermilk wastewater (BMW), and dairy wastewater (DWW), to promote biomass production and enhance the composition of bioactive compounds. By assessing various concentrations (1%, 2%, and 4% v v−1) of these byproducts in a modified growth medium, this study aims to evaluate their effect on L. platensis growth, phycocyanin (C-PC) content, and fatty acid methyl ester (FAME) profiles. The results show that the optimal biomass production was achieved with 2% scotta and dairy wastewater, reaching maximum concentrations of 3.30 g L−1 and 3.19 g L−1, respectively. Mixotrophic cultivation led to increased C-PC yields, especially in buttermilk and dairy wastewater treatments, highlighting the potential for producing valuable pigments. Additionally, the FAME profiles indicated minimal changes compared to the control, with oleic and γ-linolenic acids being dominant in mixotrophic conditions. These findings support the viability of utilizing dairy byproducts for sustainable L. platensis cultivation, contributing to a circular bioeconomy while producing bioactive compounds of nutritional and commercial interest.