Project description:This study identified and compared the bacterial diversity and the antimicrobial resistance profile of clinically relevant isolates around a newly developed hospital and university precinct
Project description:Background: Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation (LPO), represents a promising therapeutic strategy. Magnolia officinalis, a traditional herb for resolving dampness and phlegm, is known to modulate cellular metabolism. While magnolol (MAG), a bioactive neolignan from Magnolia officinalis, shows anti-TNBC activity, its role in inducing ferroptosis remains unexplored. Methods: Anti-TNBC effects of MAG were assessed in MDA-MB-231 and 4T1 cells via viability, apoptosis, and ferroptosis assays (intracellular Fe²⁺, LPO, GSH). Target identification employed network pharmacology, RNA-seq, surface plasmon resonance, and pull-down assays. Mechanisms were validated using siRNA/overexpression, Co-IP, and immunofluorescence. In vivo efficacy was evaluated in xenograft models. Results: MAG inhibited proliferation and induced apoptosis and ferroptosis in TNBC cells, evidenced by elevated Fe²⁺ and lipid peroxidation, depleted GSH, downregulated SLC7A11/GPX4, and mitochondrial shrinkage effects reversed by ferroptosis inhibitors. MAG directly bound and suppressed transcription factor ETS2. ETS2 knockdown sensitized cells to MAG-induced ferroptosis, while its overexpression restored SLC7A11/GPX4 expression and conferred resistance. Mechanistically, ETS2 transcriptionally regulated SLC7A11, and MAG enhanced ETS2-SLC7A11 protein interaction. In vivo, MAG significantly suppressed tumor growth with low toxicity and downregulated ETS2, SLC7A11, and GPX4. Conclusions: MAG induces ferroptosis in MDA-MB-231 cells, which may be mediated by targeting the ETS2/SLC7A11/GPX4 signaling axis, providing mechanistic insights into its anti-TNBC activity.
2026-07-27 | GSE341147 | GEO
Project description:Exploring Antimicrobial Resistance Genes in an Urban Coati (Nasua nasua)
Project description:In this paper we investigated the mechanism of action of Maganin-2 (Mag-2), a well-known antimicrobial peptide isolated from the African clawed frog Xenopus laevis, by functional proteomic approaches. Several proteins belonging to E. coli macromolecular membrane complexes were identified as Mag-2 putative interactors. Among these, we focused our attention on BamA a membrane protein belonging to the BAM complex responsible for the folding and insertion of nascent β‐barrel Outer Membrane Proteins (OMPs) in the outer membrane. In silico predictions by molecular modelling and in vitro fluorescence binding and Light Scattering experiments carried out using a recombinant form of BamA confirmed the formation of a stable Mag-2/BamA complex and indicated a high affinity of the peptide for BamA. The functional implications of these interactions were investigated by two alternative and complementary approaches. The number of outer membrane proteins OmpA and OmpF produced in E. coli following Mag-2 incubation was evaluated by both western blot analysis and quantitative tandem mass spectrometry in MRM scan mode. In both experiments, a gradual decrease in outer membrane protein production with time was observed because of Mag-2 treatment.
Project description:Mouse androgenetic haploid embryonic stem cells (mAG-haESCs) can be utilized to uncover gene functions, especially those of genes with recessive effects, and to produce semicloned mice when injected into mature oocytes. However, mouse haploid cells undergo rapid diploidization during long-term culture in vitro and subsequently lose the advantages of haploidy and the factors that drive diploidization are not well understood. In this study, we compared the small RNAs (sRNAs) of mAG-haESCs, normal ESCs and mouse round spermatids by high-throughput sequencing and identified distinct sRNA profiles. Several let-7 family members and miR-290-295 cluster miRNAs were found significantly differentially transcribed. Knockdown and overexpression experiments showed that let-7a and let-7g suppress diploidization while miR-290a facilitates diploidization. Our study revealed the unique sRNA profile of mAG-haESCs and demonstrated that let-7a overexpression can mitigate diploidization in mAG-haESCs. These findings will help us to better understand mAG-haESCs and utilize them as a tool in the future.