RESUMEN
Rhodomyrtus tomentosa is a source of a novel antibiotic, rhodomyrtone. Because of the increasing industrial demand for this compound, germplasm with a high rhodomyrtone content is the key to sustainable future cultivation. In this study, rhodomyrtone genotypes were verified using the plastid genomic region marker matK and nuclear ribosomal internal transcribed spacer ITS. These two DNA barcodes proved to be useful tools for identifying different rhodomyrtone contents via the SNP haplotypes C569T and A561G, respectively. The results were correlated with rhodomyrtone content determined via HPLC. Subsequently, R. tomentosa samples with high- and low-rhodomyrtone genotypes were collected for de novo transcriptome and gene expression analyses. A total of 83,402 unigenes were classified into 25 KOG classifications, and 74,102 annotated unigenes were obtained. Analysis of differential gene expression between samples or groups using DESeq2 revealed highly expressed levels related to rhodomyrtone content in two genotypes. semiquantitative RT-PCR further revealed that the high rhodomyrtone content in these two genotypes correlated with expression of zinc transporter protein (RtZnT). In addition, we found that expression of RtZnT resulted in increased sensitivity of R. tomentosa under ZnSO4 stress. The findings provide useful information for selection of cultivation sites to achieve high rhodomyrtone yields in R. tomentosa.
RESUMEN
BACKGROUND: LIV1 is a transmembrane protein that may become a new therapeutic target through the development of antibody-drug conjugates (ADCs). Few studies are available regarding the assessment of LIV1 expression in clinical breast cancer (BC) samples. METHODS: We analyzed LIV1 mRNA expression in 8982 primary BC. We searched for correlations between LIV1 expression and clinicopathological data, including disease-free survival (DFS), overall survival (OS), pathological complete response to chemotherapy (pCR), and potential vulnerability and actionability to anti-cancer drugs used or under development in BC. Analyses were performed in the whole population and each molecular subtype separately. RESULTS: LIV1 expression was associated with good-prognosis features and with longer DFS and OS in multivariate analysis. However, patients with high LIV1 expression displayed a lower pCR rate than patients with low expression after anthracycline-based neoadjuvant chemotherapy, including in multivariate analysis adjusted on grade and molecular subtypes. LIV1-high tumors were associated with higher probabilities of sensitivity to hormone therapy and CDK4/6 inhibitors and lower probabilities of sensitivity to immune-checkpoint inhibitors and PARP inhibitors. These observations were different according to the molecular subtypes when analyzed separately. CONCLUSIONS: These results may provide novel insights into the clinical development and use of LIV1-targeted ADCs by identifying prognostic and predictive value of LIV1 expression in each molecular subtype and associated vulnerability to other systemic therapies.
RESUMEN
The present study was conducted to explore the bioavailability of chitosan-zinc chelate (CS-Zn) in weaned piglets, and its characteristics of prepared and oral safety were also involved. A total of 210 crossbred weaned piglets (Duroc × Landrace × Large White) with a mean body weight of 6.30 kg were randomly assigned into seven dietary treatments involving a 2 × 3 factorial arrangement with two Zn sources (CS-Zn and ZnSO4) and three levels of added Zn (50, 100, 150 mg Zn/kg) plus a Zn-unsupplemented control diet. The feeding trial lasted 42 days. The AFM image of CS-Zn showed a rougher appearance and smaller size particles. The changes in spectrum peaks evidenced the successful chelating of Zn2+ with chitosan. The XRD patterns revealed the formation of a new crystalline phase. Moreover, the oral acute toxicity test of CS-Zn showed no lethal effects on mice. Weaned piglets fed dietary CS-Zn showed improved weight gain and decreased diarrhea incidence. Additionally, the bioavailability of CS-Zn was higher than that of ZnSO4 in piglets. Taken together, these results indicate that the prepared CS-Zn chelate, with rough surface and crystalline phase, is non-toxic and show enhanced bioavailability.
RESUMEN
Intracellular zinc homeostasis is tightly regulated under physiological conditions; however, dysregulation of zinc levels has been reported in various chronic inflammatory and malignant diseases. In this study, we aimed to assess the expression pattern of the 24 currently known zinc transporters in resting and stimulated human peripheral blood mononuclear cells (PBMCs). The cells were isolated from healthy probands and subsequently stimulated with phytohaemagglutinin (PHA) for 3 days. The expression levels of zinc transporters [Zrt/IRT-like protein (ZIP) and cation diffusion facilitator/zinc transporter protein (CDF/ZnT) families] were analyzed by quantitative reverse transcription-polymerase chain reaction. Of the 24 genes encoding for zinc transporters, 19 were found to be ubiquitously expressed in PBMCs. ZIP5 and ZnT10 were not found in all 5 samples, whereas ZIP12, ZnT3 and ZIP2 were expressed in only 1-2 out of 5 PBMC samples. Of note, stimulation by PHA led to an overall downregulation of zinc transporters in the PBMCs of 4 out of the 5 subjects. Notably, the transcript levels of ZIP14 were consistently induced and those of ZIP3 and ZIP4 consistently downregulated in all 5 subjects, whereas the corresponding levels of the remaining 21 genes varied. Data from this study may facilitate a better understanding of the pathophysiological role of deregulated zinc transporters in chronic inflammatory diseases.