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Marine microalgae are considered a potentially new and valuable source of biologically active molecules for applications in the food industry as well as in the pharmaceutical, nutraceutical, and cosmetic sectors. They can be easily cultured, have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. In this study, 21 diatoms, 7 dinoflagellates, and 4 flagellate species were grown in three different culturing conditions and the corresponding extracts were tested for possible antioxidant, anti-inflammatory, anticancer, anti-diabetes, antibacterial, and anti-biofilm activities. In addition, for three diatoms we also tested two different clones to disclose diversity in clone bioactivity. Six diatom species displayed specific anti-inflammatory, anticancer (blocking human melanoma cell proliferation), and anti-biofilm (against the bacteria Staphylococcus epidermidis) activities whereas, none of the other microalgae were bioactive against the conditions tested for. Furthermore, none of the 6 diatom species tested were toxic on normal human cells. Culturing conditions (i.e., nutrient starvation conditions) greatly influenced bioactivity of the majority of the clones/species tested. This study denotes the potential of diatoms as sources of promising bioactives for the treatment of human pathologies.

Microalgae have been shown to be excellent producers of lipids, pigments, carbohydrates, and a plethora of secondary metabolites with possible applications in the pharmacological, nutraceutical, and cosmeceutical sectors. Recently, various microalgal raw extracts have been found to have anti-inflammatory properties. In this study, we performed the fractionation of raw extracts of the diatom Cylindrotheca closterium, previously shown to have anti-inflammatory properties, obtaining five fractions. Fractions C and D were found to significantly inhibit tumor necrosis factor alpha (TNF-⍺) release in LPS-stimulated human monocyte THP-1 cells. A dereplication analysis of these two fractions allowed the identification of their main components. Our data suggest that lysophosphatidylcholines and a breakdown product of chlorophyll, pheophorbide a, were probably responsible for the observed anti-inflammatory activity. Pheophorbide a is known to have anti-inflammatory properties. We tested and confirmed the anti-inflammatory activity of 1-palmitoyl-sn-glycero-3-phosphocholine, the most abundant lysophosphatidylcholine found in fraction C. This study demonstrated the importance of proper dereplication of bioactive extracts and fractions before isolation of compounds is commenced

Systemic lupus erythematosus (SLE) imposes a great burden on the lives of patients. Patients’ and physicians’ concerns about the disease diverge considerably. Physicians focus on controlling disease activity to prevent damage accrual, while patients focus on symptoms that impact on health-related quality of life (HRQoL). The existing clinician reported outcomes (ClinRO), such as disease activity indices, remission, low disease activity (LLDAS), response (SRI and BICLA) do not include the patient perspective.Several investigations show that patients judged in remission by the treating physician, still report the presence of relevant clinical symptoms.1 2Patients and physicians assess the disease differently (discordance up to 58% of cases)Patients tend to score disease activity higher than physiciansPatients consider subjective manifestations as more relevant than physiciansPhysicians consider laboratory abnormalities as more relevantIt seems there is a discordance between patients and physicians when it comes to prioritising outcomes.The best way to identify the patients’ priorities is through Patient Reported Outcomes (PROs). PROs allow us to capture aspects of the disease which have an impact on patients and constitute their burden of the disease. Ideally, the dialogue between doctor and patient should address the most bothersome symptoms for the individual patient. What is most bothersome for one might not be the same as for someone else and it most likely won´t be the same priority as the doctor has. At the same time, some of the most bothersome symptoms are difficult (if not impossible) to manage with traditional SLE treatments. In these cases, the communication becomes even more important, and a communication gap can be detrimental to the HRQoL and overall care.3Yen JC, et al. Discordance between patients and their physicians in the assessment of lupus disease activity: relevance for clinical trials. Lupus. 1999;8(8):660–70. doi: 10.1191/096120399680411362.Cornet A, et al. Living with systemic lupus erythematosus in 2020: a European patient survey. Lupus Sci Med. 2021 Apr;8(1):e000469. doi: 10.1136/lupus-2020-000469. PMID: 33849920; PMCID: PMC8051432.Cornet A, et al. Patient-doctor communication gap - results of a speed-shop on ‘lupus flare’ at lupus 2022 meetings. Ann Rheum Dis. 2023;82:309. POS0171.Learning ObjectivesDescribe the burden of the disease from the patient´s perspectiveExplain the importance of patient-physician communicationDistinguish between patient and physician priorities

Systemic lupus erythematosus (SLE) is a very complicated and heterogeneous disease, and the popular saying is that no two lupus patients are the same. This of course also means that the treatment and planning of care can be very complicated and needs to be adjusted to the individual patient. One of the best ways to achieve this goal is through shared decision making. If the patient feels like they have a voice in the treatment plans the probability of treatment adherence increases substantially. On average the SLE patient is more aware of their own symptoms, disease progression and medication than patients with less complicated or less heterogeneous diseases. They need to become experts in their disease because they are the ones living with the symptoms and can often ‘feel’ a flare coming on before the laboratory results show it. Health-related-quality of life (HRQoL) when living with a chronic disease like SLE very much depends on how you self-manage; living a healthy life, keeping active, prioritising everyday tasks according to energy-level etc. The engaged and informed patient can be both a help and a burden when it comes to the physican´s disease management. It helps if the patient has the right medical information and respects that the physician has the expertise to decide what is best for them.1 A patient needs to know that not every symptom is because of lupus and that they might not be flaring, even though they feel like they are. This ‘complicated’ care of an SLE patient often takes more than one health care professional. Apart from a multidisciplinary team of physicians each specialised in their own manifestations (like kidneys, lungs, heart etc.) it is often beneficial to involve other areas such as specialised nurses, physiotherapists, psychologists, occupational therapists etc. This multidisciplinary team of course requires a good coordination, which should not be put exclusively on the patient.Cornet A, et al. Patients expectations, and what we (can) do about it. Lupus Sci Med.2020;7:doi:10.1136/lupus-2020-eurolupus.7.Learning ObjectivesExplain the importance of involving patients in shared-decision-makingDescribe how a multidisciplinary team can be used in the SLE careDescribe the role of the informed patient in their own care

Enzymatic degradation of algae cell wall carbohydrates by microorganisms is under increasing investigation as marine organic matter gains more value as a sustainable resource. The fate of carbon in the marine ecosystem is in part driven by these degradation processes. In this study, we observe the microbiome dynamics of the macroalga Fucus vesiculosus in 25-day-enrichment cultures resulting in partial degradation of the brown algae. Microbial community analyses revealed the phylum Pseudomonadota as the main bacterial fraction dominated by the genera Marinomonas and Vibrio. More importantly, a metagenome-based Hidden Markov model for specifc glycosyl hydrolyses and sulphatases identifed Bacteroidota as the phylum with the highest potential for cell wall degradation, contrary to their low abundance. For experimental verifcation, we cloned, expressed, and biochemically characterised two α-L-fucosidases, FUJM18 and FUJM20. While protein structure predictions suggest the highest similarity to a Bacillota origin, protein–protein blasts solely showed weak similarities to defned Bacteroidota proteins. Both enzymes were remarkably active at elevated temperatures and are the basis for a potential synthetic enzyme cocktail for large-scale algal destruction.

Turgencin A, a potent antimicrobial peptide isolated from the Arctic sea squirt Synoicum turgens, consists of 36 amino acid residues and three disulfide bridges, making it challenging to synthesize. The aim of the present study was to develop a truncated peptide with an antimicrobial drug lead potential based on turgencin A. The experiments consisted of: (1) sequence analysis and prediction of antimicrobial potential of truncated 10-mer sequences; (2) synthesis and antimicrobial screening of a lead peptide devoid of the cysteine residues; (3) optimization of in vitro antimicrobial activity of the lead peptide using an amino acid replacement strategy; and (4) screening the synthesized peptides for cytotoxic activities. In silico analysis of turgencin A using various prediction software indicated an internal, cationic 10-mer sequence to be putatively antimicrobial. The synthesized truncated lead peptide displayed weak antimicrobial activity. However, by following a systematic amino acid replacement strategy, a modified peptide was developed that retained the potency of the original peptide. The optimized peptide StAMP-9 displayed bactericidal activity, with minimal inhibitory concentrations of 7.8 µg/mL against Staphylococcus aureus and 3.9 µg/mL against Escherichia coli, and no cytotoxic effects against mammalian cells. Preliminary experiments indicate the bacterial membranes as immediate and primary targets.

ObjectiveThe aim of this study was to analyse the 2020 burden of Systemic Lupus Erythematosus (SLE) in Europe, from the patients’ perspective.MethodsIn May 2020, Lupus Europe, the European umbrella patient association for SLE, designed and disseminated a multilingual anonymous online survey to individuals with a self-reported physician’s diagnosis of SLE living in Europe.ResultsData from 4375 SLE survey respondents (95.9% women, median age: 45 (IQR: 36–54) years, 70.7% Caucasians) from 35 European countries were analysed. The median age at SLE diagnosis was 30 years (IQR: 22–40) and the median diagnosis delay was 2 years (IQR: 0–6). The most commonly affected organ-systems included the joints (81.8%) and skin (59.4%), with renal involvement in 30%. Another diagnosis was given before that of SLE in 45.0%, including psychological/mental disorders in 9.1% and fibromyalgia in 5.9%. The median number of symptoms reported was 9 (IQR: 6–11) out of 21, with fatigue most common (85.3%) and most bothersome. The median number of SLE-related medications was 5 (IQR: 3–7), including antimalarials (75%), oral glucocorticoids (52.4%), immunosuppressants (39.8%) and biologics (10.9%). Respondents reported significant impact over their studies, career and emotional/sexual life in 50.7%, 57.9% and 38.2%, respectively. Appropriate access to care was highly variable across countries and care component.ConclusionThis survey underlines the 2020 burden and strong heterogeneity in the care of SLE across Europe, from the patient’s perspective. Altogether, these data may prove crucial to physicians, patients and policy-makers to improve the diagnosis and management of this rare and complex disease.

The marine environment is a rich source of biodiversity, including microorganisms that have proven to be prolific producers of bioactive secondary metabolites. Arctic seas are less explored than warmer, more accessible areas, providing a promising starting point to search for novel bioactive compounds. In the present work, an Arctic marine Pseudomonas sp. belonging to the Pseudomonas (P.) fluorescence group was cultivated in four different media in an attempt to activate biosynthetic pathways leading to the production of antibacterial and anticancer compounds. Culture extracts were pre-fractionated and screened for antibacterial and anticancer activities. One fraction from three of the four growth conditions showed inhibitory activity towards bacteria and cancer cells. The active fractions were dereplicated using molecular networking based on MS/MS fragmentation data, indicating the presence of a cluster of related rhamnolipids. Six compounds were isolated using HPLC and mass-guided fractionation, and by interpreting data from NMR and high-resolution MS/MS analysis; the structures of the compounds were determined to be five mono-rhamnolipids and the lipid moiety of one of the rhamnolipids. Molecular networking proved to be a valuable tool for dereplication of these related compounds, and for the first time, five mono-rhamnolipids from a bacterium within the P. fluorescence group were characterized, including one new mono-rhamnolipid.

Streptomyces remains one of the prolific sources of structural diversity, and a reservoir to mine for novel natural products. Continued screening for new Streptomyces strains in our laboratory led to the isolation of Streptomyces sp. RK44 from the underexplored areas of Kintampo waterfalls, Ghana, Africa. Preliminary screening of the metabolites from this strain resulted in the characterization of a new 2-alkyl-4-hydroxymethylfuran carboxamide (AHFA) together with five known compounds, cyclo-(L-Pro-Gly), cyclo-(L-Pro-L-Phe), cyclo-(L-Pro-L-Val), cyclo-(L-Leu-Hyp), and deferoxamine E. AHFA, a methylenomycin (MMF) homolog, exhibited anti-proliferative activity (EC50 = 89.6 µM) against melanoma A2058 cell lines. This activity, albeit weak is the first report amongst MMFs. Furthermore, the putative biosynthetic gene cluster (ahfa) was identified for the biosynthesis of AHFA 1. DFO-E 6 displayed potent anti-plasmodial activity (IC50 = 1.08 µM) against P. falciparum 3D7. High-resolution electrospray ionization mass spectrometry (HR ESIMS) and molecular network assisted the targeted-isolation process, and tentatively identified six AHFA analogues, and six siderophores.

Marine organisms possess the capacity to produce a variety of unique and biologically potent natural products for treating human diseases, many of which are currently commercially available or are in advanced clinical trials. Here we provide a short review on progress in the field and discuss a case study of an EU-funded project, PharmaSea, which aims to discover novel products for the treatment of infections, inflammation and neurodegenerative diseases. Research in this sector is opening new doors for harnessing the potential of marine natural products with pharmaceutical properties.