Correction: Screening for osteogenic activity in extracts from Irish marine organisms: The potential of Ceramium pallidum.

[This corrects the article DOI: 10.1371/journal.pone.0207303.].

Screening for osteogenic activity in extracts from Irish marine organisms: The potential of Ceramium pallidum.

Extracts and compounds derived from marine organisms have reportedly shown some osteogenic potential. As such, these bioactives may aid in the treatment of musculoskeletal conditions such as osteoporosis; helping to address inefficacies with current treatment options. In this study, 72 fractions were tested for their in vitro osteogenic activity using a human foetal osteoblast (hFOB) cell line and bone marrow derived mesenchymal stem cells (MSCs), focusing on their cytotoxic, proliferative and differentiation effects. Extracts dissolved in dimethyl sulfoxide and ethanol showed no significant osteogenic potential. However, two extracts derived from powder residues (left over from original organic extractions) caused a significant promotion of MSC differentiation. Bioactivity from powder residues derived from the epiphytic red algae Ceramium pallidum is described in detail to highlight its treatment potential. In vitro, C. pallidum was shown to promote MSC differentiation and extracellular matrix mineralisation. In vivo, this extract caused a significant increase in opercular bone growth of zebrafish larvae and a significant increase in bone density of regenerated adult caudal fins. Our findings therefore show the importance of continued screening efforts, particularly of novel extract sources, and the presence of bioactive compounds in C. pallidum extract.

Red algal extracts from Plocamium lyngbyanum and Ceramium secundatum stimulate osteogenic activities in vitro and bone growth in zebrafish larvae.

Through the current trend for bioprospecting, marine organisms - particularly algae - are becoming increasingly known for their osteogenic potential. Such organisms may provide novel treatment options for osteoporosis and other musculoskeletal conditions, helping to address their large healthcare burden and the limitations of current therapies. In this study, extracts from two red algae - Plocamium lyngbyanum and Ceramium secundatum - were tested in vitro and in vivo for their osteogenic potential. In vitro, the growth of human bone marrow stromal cells (hBMSCs) was significantly greater in the presence of the extracts, particularly with P. lyngbyanum treatment. Osteogenic differentiation was promoted more by C. secundatum (70 µg/ml), though P. lyngbyanum had greater in vitro mineralisation potential. Both species caused a marked and dose-dependent increase in the opercular bone area of zebrafish larvae. Our findings therefore indicate the presence of bioactive components in P. lyngbyanum and C. secundatum extracts, which can promote both in vitro and in vivo osteogenic activity.

Sulfated steroid-amino acid conjugates from the Irish marine sponge Polymastia boletiformis.

Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2). Extensive 1D and 2D NMR analyses in combination with quantum mechanical calculations of the electronic circular dichroism (ECD) spectra, optical rotation, and 13C chemical shifts were used to establish the chemical structures of 1 and 2. Both compounds exhibited moderate antifungal activity against Cladosporium cucumerinum, while compound 2 was also active against Candida albicans. Marine natural products containing steroidal and amino acid constituents are extremely rare in nature.

Urinary excretion of calcium and phosphate in preterm infants.

The aims of this study were to determine reference ranges for the urinary calcium (UCa/Cr) and phosphate (UPO(4)/Cr) creatinine ratios and to study factors influencing these ratios in a representative population of preterm infants managed according to current nutritional guidelines. Spot urine samples were obtained from 186 preterm infants (gestation 24-34 weeks) for measurement of UCa/Cr and UPO(4)/Cr ratios as part of a routine metabolic bone screening program, once every 2-4 weeks from the 3rd to the 18th week of life. Data were also collected on gender, appropriate or small for gestational age (SGA), nutrition [total parenteral nutrition (TPN), preterm or term formula, and breast milk], plasma Ca, P0(4), urea, and electrolytes and on the use of drugs (frusemide, dexamethasone, and theophylline). Data from infants treated with any of these three drugs were analyzed separately and not included in establishing the reference ranges for UCa/Cr and UPO(4)/Cr. The mean gestational age of the study population was 28 weeks (range 24-34 weeks). The 95th percentile for UCa/Cr at 3 weeks of age was 3.8 mmol/mmol and decreased significantly with increasing postnatal age (P<0.001). The 95th per-centile for UPO(4)/Cr was 26.69 mmol/mmol at 3 weeks of age, but this did not change significantly with increasing postnatal age (P=0.296). On univariate analysis there was no significant association of UCa/Cr and UPO(4)/Cr with gender and type of enteral nutrition. The UCa/Cr was lower in infants who were SGA (P=0.013) and with low plasma Ca (P=0.008). Infants on TPN had significantly higher UCa/Cr (P =0.019) and lower UPO(4)/Cr ratios(P<0.001). Multivariate analysis confirmed the decrease in UCa/Cr ratio with increasing postnatal age, but the SGA effect was eliminated. The use of furosemide(P<0.001) and theophylline (P=0.003) was associated with a significant increase in the UCa/Cr ratio. The use of dexamethasone was also associated with an increase in UCa/Cr ratio, but this did not achieve statistical significance (P=0.339). The use of furosemide, theophylline,and dexamethasone had no effect on UPO(4)/Cr. We report a reference range for UCa/Cr and UPO(4)/Cr ratios and factors influencing these ratios in a representative population of preterm infants between 24 and 34 weeks gestation, managed according to current nutritional guide-lines.