Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention.

The development of chemopreventive strategies with the ability to prevent the progression of lung lesions to malignant cancers would reduce the mortality and morbidity resulting from this deadly disease. Delivery of microRNA (miRNA) by inhalation is a novel method for lung cancer prevention. In this study, we investigated the combined efficacy of aerosolized miR-138-5p and miR-200c miRNA mimics in lung cancer prevention. Combination of the two miRNAs inhibited Benzo(a)pyrene (B((a))P)-induced lung adenomas and N-nitroso-tris-chloroethylurea (NTCU)-induced lung squamous cell carcinomas with no detectable side effects. Using single-cell RNA sequencing (scRNA-seq) and imaging mass cytometry (IMC), we found that both miRNAs inhibited programmed cell death ligand 1 (PD-L1) expression. Our flow cytometry results showed that aerosolized delivery of combined miRNAs increased CD4+ and CD8+ T cells and reduced the expression of programmed cell death protein 1 (PD-1) and T-regulatory cells. Our results demonstrated that the delivery of aerosolized microRNAs targeting PD-L1 can be highly effective in preventing lung cancer development and progression in mice.

Functional Haplotype and eQTL Analyses of Genes Affecting Cadmium Content in Cultivated Rice.

BACKGROUND: Rice is a major food resource for Asian countries including Korea. However, most Asian countries are facing food safety problems due to cropland contamination by heavy metals. Thus, this study was conducted to investigate genetic factors affecting the expression of cadmium (Cd) gene, and to confirm differences in Cd translocation among cultivars because the current molecular understanding of Cd uptake-transport mechanisms remains insufficient. Associations between genotypes and gene expression level of Cd-related genes such as NRAMP, MTP, and HMA gene families in the rice core collection were analyzed at the genomic level. RESULTS: Os01g0956700, Os05g0128400 and Os11g0485200 showed strong associations between expression level and genotype in the rice core collection, the regulatory factors that associated with these genes in cis and trans were founded. The association between the expression level and genotype of the candidate gene (Os01g0611300: metal tolerance protein) predicted to affect Cd content in rice by a previous genome-wide association study (GWAS) was also analyzed. Furthermore, as a result of the phylogeny and haplotype analyses of the candidate gene, high-Cd tolerance cultivars were selected. The correlations between Cd and other inorganic components (Mg, Mn, Fe, Cu and Zn) in the roots, stems, leaves and unpolished grain of selected rice cultivars were analyzed. CONCLUSION: Therefore, these results may be useful for understanding the uptake-transport mechanisms of Cd and other inorganic components via molecular genetics and may help rice breeders develop new low-Cd cultivars in the near future.

Idiopathic thoracic epidural lipomatosis with chest pain.

Spinal epidural lipomatosis (SEL) is an overgrowth of the normally encapsulated adipose tissue in the epidural space around the spinal cord in the thoracic and lumbar spine causing compression of the neural components. Idiopathic SEL in non-obese patients is exceptional. Idiopathic SEL can result in thoracic myelopathy and lumbar radiculopathy. A thoracic radiculopathy due to idiopathic SEL has not been reported yet. We report a case of idiopathic SEL with intractable chest pain and paresthesia. We suggest that idiopathic SEL should be considered as a cause of chest pain.