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Hydroxysafflor yellow A (HSYA), an active ingredient extracted from Carthami flos, shows potential for treating ischemic stroke. This phase 1 study assessed the safety, tolerability, and pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers who received intravenous infusions of pure HSYA powder. The study comprised 2 parts. Part A was a randomized, double-blind, placebo-controlled dose-escalation study that evaluated safety and tolerability. This included a single-dose study with 7 dose levels of HSYA (6.25, 12.5, 25, 50, 75, 100, and 125 mg) in 52 volunteers, and a multidose study (100 and 125 mg) in 16 volunteers. Part B was an open-label study where 12 volunteers received 75 mg of HSYA once daily for 14 consecutive days to examine PKs. There were no adverse events (AEs) leading to treatment discontinuation by HSYA throughout the treatment period. All reported AEs were mild and did not require special treatment. PK analysis revealed rapid absorption (median T max of 1.1 hours) and elimination (median t 1/2 4.0 and 4.7 hours) of HSYA. Total body clearance on the 1st and 14th days was 1.7 and 1.6 L/h, respectively., (© 2024 The Author(s). Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

The Macau storage reservoir (MSR) has experienced algal blooms in recent years, with high levels of Cylindrospermopsis and Microcystis and detectable concentrations of cyanotoxins. To analyze the cyanotoxin-producing genotypes and relate the corresponding cyanotoxins to the water quality parameters, a quantitative real-time polymerase chain reaction was developed and applied to the water samples in three locations of MSR. Cylindrospermopsin polyketide synthetase ( pks) gene and a series of microcystin synthetase ( mcy) genes were used for identifying and quantifying cylindrospermopsin- and microcystin-producing genes, and the corresponding water parameters were measured accordingly. Our results showed that high concentrations of cylindrospermopsin and low concentrations of microcystin were measured during the study period. There was a strong correlation between the pks gene numbers and cylindrospermopsin concentrations ( R = 0.95), while weak correlations were obtained between the mcy genes numbers and microcystin concentrations. Furthermore, the pks gene numbers were strongly related to Cylindrospermopsis ( R = 0.88), cyanobacterial cell numbers ( R = 0.96), total algae numbers ( R = 0.95), and chlorophyll- a concentrations ( R = 0.83), consistent with the dominant species of Cylindrospermopsis among the cyanobacteria existing in MSR. NH-N ( R = 0.68) and pH ( R = 0.89) were the water quality parameters most highly correlated with the pks gene numbers. These results contribute to monitoring for potential cyanotoxins in raw water. [ABSTRACT FROM AUTHOR]

The diversity and secondary metabolite potential of culturable actinomycetes associated with eight different marine sponges collected from the South China Sea and the Yellow sea were investigated. A total of 327 strains were isolated and 108 representative isolates were selected for phylogenetic analysis. Ten families and 13 genera of Actinomycetales were detected, among which five genera represent first records isolated from marine sponges. Oligotrophic medium M5 (water agar) proved to be efficient for selective isolation, and ?Micromonospora-Streptomyces? was proposed as the major distribution group of sponge-associated actinomycetes from the China Seas. Ten isolates are likely to represent novel species. Sponge Hymeniacidon perleve was found to contain the highest genus diversity (seven genera) of actinomycetes. Housekeeping gene phylogenetic analyses of the isolates indicated one ubiquitous Micromonospora species, one unique Streptomyces species and one unique Verrucosispora phylogroup. Of the isolates, 27.5% displayed antimicrobial activity, and 91% contained polyketide synthase and/or nonribosomal peptide synthetase genes, indicating that these isolates had a high potential to produce secondary metabolites. The isolates from sponge Axinella sp. contained the highest presence of both antimicrobial activity and NRPS genes, while those from isolation medium DNBA showed the highest presence of antimicrobial activity and PKS I genes. [ABSTRACT FROM AUTHOR]

Sponge-derived bacteria are considered to be a promising source of novel drugs, owing to their abundant secondary metabolites that have diverse biological activities. In this study, we explored the antimicrobial biosynthetic potential and phylogenetics of culturable bacteria associated with the sponge Ophlitaspongia sp. from the Yellow Sea, China. Using culture-dependent methods, we obtained 151 bacterial strains, which were then analysed for their antimicrobial activities against seven indicator strains. The results indicate that 94 (62.3%) of the 151 isolated strains exhibited antimicrobial activities and inhibited at least one of the indicator strains. Fifty-two strains were selected for further phylogenetic analysis using 16S rRNA gene sequencing, as well as for the presence of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes. These 52 strains belonged to 20 genera from 18 families in 4 phyla, including Actinobacteria , Bacteroidetes , Firmicutes , and Proteobacteria . Five strains with PKS genes and ten strains with NRPS genes were detected. Among them, two strains contained both PKS and NRPS genes. Notoacmeibacter sp. strain HMA008 (class Alphaproteobacteria ) exhibited potent antimicrobial activity; thus, whole genome sequencing methods were used to analyse its secondary metabolite biosynthetic gene clusters. The genome of HMA008 contained 12 biosynthetic gene clusters that potentially encode secondary metabolites belonging to compound classes such as non-ribosomal peptides, prodigiosin, terpene, β-lactones, and siderophore, among others. This study indicates that the sponge Ophlitaspongia sp. harbours diverse bacterial strains with antimicrobial properties and may serve as a potential source of bioactive compounds.