Lipid nanoparticles (LNPs), composed of ionized lipids, helper lipids, and cholesterol, provide general therapeutic effects by facilitating intracellular transport and avoiding endosomal compartments. LNP-based drug delivery has great potential for the development of novel gene therapies and effective vaccines. Solid lipid nanoparticles (SLNs) are derived from physiologically acceptable lipid components and remain robust at body temperature, thereby providing high structural stability and biocompatibility. By enhancing drug delivery through blood vessels, SLNs have been used to improve the efficacy of cancer treatments. Breast cancer, the most common malignancy in women, has a declining mortality rate but remains incurable. Recently, as an anticancer drug delivery system, SLNs have been widely used in breast cancer, improving the therapeutic efficacy of drugs. In this review, we discuss the latest advances of SLNs for breast cancer treatment and their potential in clinical use.
In many cancers, a stem-like cell subpopulation mediates tumor initiation, dissemination and drug resistance. Here, we report that cancer stem cell (CSC) abundance is transcriptionally regulated by C-terminally phosphorylated p27 (p27pT157pT198). Mechanistically, this arises through p27 co-recruitment with STAT3/CBP to gene regulators of CSC self-renewal including MYC, the Notch ligand JAG1, and ANGPTL4. p27pTpT/STAT3 also recruits a SIN3A/HDAC1 complex to co-repress the Pyk2 inhibitor, PTPN12. Pyk2, in turn, activates STAT3, creating a feed-forward loop increasing stem-like properties in vitro and tumor-initiating stem cells in vivo. The p27-activated gene profile is over-represented in STAT3 activated human breast cancers. Furthermore, mammary transgenic expression of phosphomimetic, cyclin-CDK-binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis, yielding hyperplasia and microinvasive cancers that can metastasize to liver, further supporting a role for p27pTpT in CSC expansion. Thus, p27pTpT interacts with STAT3, driving transcriptional programs governing stem cell expansion or maintenance in normal and cancer tissues.
NA4/NA6, an intermediate degradation product of β-agarase, is a high value-added product with anticancer, anti-obesity, and anti-diabetic effects. Therefore, a method that enables the efficient production of NA4/NA6 would be useful from economic and medical perspectives. In this study, we aimed to generate a Streptomyces coelicolor A3(2) mutant M22-2C43 that produces NA4/NA6 as a final product; this method serves as a more efficient alternative to the enzymatic conversion of β-agarase for the generation of these products. The M22-2C43 strain was generated through two rounds of mutagenesis and screening for increased β-agarase activity and effective production of NA4/NA6. We assembled the complete genomes of two mutants, M22 and M22-2C43, which were identified following a two-round screening. Large and small genetic changes were found in these two mutants, including the loss of two plasmids present in wild-type S. coelicolor A3(2) and chromosome circularization of mutant M22-2C43. These findings suggest that mutant M22-2C43 can produce NA4/NA6 as a degradation product due to functional inactivation of the dagB gene through a point mutation (G474A), ultimately preventing further degradation of NA4/NA6 to NA2. To our knowledge, this is the first report of a microbial strain that can effectively produce NA4/NA6 as the main degradation product of β-agarase, opening the door for the use of this species for the large-scale production of this valuable product.
Dermacoccus barathri is the first reported pathogen within the Dermacoccus genus to cause a catheter-related bloodstream infection, which occurred in 2015. In this study, the complete genome assembly of Dermacoccus barathri was constructed, and the complete genome of Dermacoccus barathri FBCC-B549 consists of a single chromosome (3,137,745 bp) without plasmids. The constructed genome of D. barathri was compared with those of two closely related species within the Dermacoccus genus. D. barathri exhibited a pattern similar to Dermacoccus abyssi in terms of gene clusters and synteny analysis. Contrary to previous studies, biosynthetic gene cluster (BGC) analysis for predicting secondary metabolites revealed the presence of the LAP biosynthesis pathway in the complete genome of D. barathri, predicting the potential synthesis of the secondary metabolite plantazolicin. Furthermore, an analysis to investigate the potential pathogenicity of D. barathri did not reveal any antibiotic resistance genes; however, nine virulence factors were identified in the Virulence Factor Database (VFDB). According to these matching results in the VFDB, despite identifying a few factors involved in biofilm formation, further research is required to determine the actual impact of D. barathri on pathogenicity. The complete genome of D. barathri is expected to serve as a valuable resource for future studies on D. barathri, which currently lack sufficient genomic sequence information.
Microcystis is a genus of cyanobacteria responsible for harmful algal blooms (HABs) in freshwater ecosystems, posing significant ecological and public health risks. Despite its importance, current genomic resources are heavily biased toward Microcystis aeruginosa, limiting comprehensive understanding of genomic diversity within the genus. In this study, we present the first complete genome sequences of two morphospecies, M. ichthyoblabe FBCC-A1114 and M. protocystis FBCC-A270. Using long-read sequencing, both genomes were assembled into single circular chromosomes of 5.84 Mb and 5.76 Mb, respectively. Phylogenetic analyses placed both strains within genospecies G, alongside M. aeruginosa and M. viridis. Comparative analysis of biosynthetic gene clusters revealed that, while most genospecies G members harbor aeruginosin, cyanobactin, and microviridin gene clusters, the two newly sequenced strains lack cyanobactin and microcystin clusters but retain the microginin cluster. Synteny analysis demonstrated high structural conservation between the two genomes, while notable structural variations were observed when compared with M. aeruginosa NIES-298. These findings reveal both functional and structural plasticity within the genospecies, suggesting ecotype diversification driven by environmental adaptation. The newly assembled genomes provide critical resources to refine classification frameworks and advance our understanding of Microcystis genomic diversity.