A proper intracellular delivery method with target tissue specificity is critical to utilize the full potential of therapeutic molecules including siRNAs while minimizing their side effects. Herein, we prepare four small-sized DNA tetrahedrons (sTds) by self-assembly of different sugar backbone-modified oligonucleotides and screened them to develop a platform for kidney-targeted cytosolic delivery of siRNA. An in vivo biodistribution study revealed the kidney-specific accumulation of mirror DNA tetrahedron (L-sTd). Low opsonization of L-sTd in serum appeared to avoid liver clearance and keep its size small enough to be filtered through the glomerular basement membrane (GBM). After GBM filtration, L-sTd could be delivered into tubular cells by endocytosis. The kidney preference and the tubular cell uptake property of the mirror DNA nanostructure could be successfully harnessed for kidney-targeted intracellular delivery of p53 siRNA to treat acute kidney injury (AKI) in mice. Therefore, L-sTd could be a promising platform for kidney-targeted cytosolic delivery of siRNA to treat renal diseases.

We propose a new deep learning DTA model 3DProtDTA, which utilises AlphaFold structure predictions in conjunction with the graph representation of proteins.

Summary. Aim: To analyze the expression levels of hsa-miR-30c-5p and hsa-miR-138-1 in tumors of patients with renal cell carcinoma to determine whether they could be used as diagnostic markers. Materials and Methods: The relative expression of hsa-miR-30c-5p and hsa-miR-138-1 was compared in the paired samples of kidney tumor tissue and conventionally normal tissue adjacent to the tumor. Results: We found a significant decrease in miR-30c-5p and miR-138-1 levels in tumor tissues even in the cases of early stage cancer. In addition, miR-138-1 expression was lower in renal cell carcinoma Fuhrman grade G3 + G4 as compared to Fuhrman grade G2. However, we found no association between miR-30c-5p and miR-138-1 expression in the tumors and the major clinical and pathological characteristics of renal cell carcinoma patients. Conclusions: A significant reduction in the expression levels of hsa-miR-30c-5p and hsa-miR-138-1 in renal cell carcinoma indicates the feasibility of further studies on the probable diagnostic utility of these markers.

Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) has been suspected to cause toxicity invertebrates, but its phenotypic effects and the underlying regulatory mechanism have not been fully revealed. Generally, cellular responses tightly control and affect various phenotypes. The scope of the whole organism or cellular toxicological phenotyping, however, has been limited, and quantitative analysis methods using phenotype data have not been fully established. Here, we demonstrated that fluorescence imaging of sub-organelle-based phenomic analysis together with transcriptomic profiling can enable a comprehensive understanding of correlations between molecular and phenomic events. To reveal the cellular response to TDCPP exposure, we obtained three sub-organelle images as fluorescent phenotypes. Transcriptomic perturbation data were measured from the RNA-seq experiment, and both profiling results were analyzed together. Interestingly, organelle phenomic data showed a unique fluorescent intensity increase in the endoplasmic reticulum (ER), and pathway analysis using transcriptomic data also revealed that ER was significantly enriched in gene ontology terms. Following the series of analyses, RNA-seq data also revealed potential carcinogenic effects of TDCPP. Our multi-dimensional profiling approach for organophosphate chemicals can uniquely correlate phenotypic changes with transcriptomic perturbations.