Identification of TRPC6 as a Novel Diagnostic Biomarker of PM-Induced Chronic Obstructive Pulmonary Disease Using Machine Learning Models.

Chronic obstructive pulmonary disease (COPD) was the third most prevalent cause of mortality worldwide in 2010; it results from a progressive and fatal deterioration of lung function because of cigarette smoking and particulate matter (PM). Therefore, it is important to identify molecular biomarkers that can diagnose the COPD phenotype to plan therapeutic efficacy. To identify potential novel biomarkers of COPD, we first obtained COPD and the normal lung tissue gene expression dataset GSE151052 from the NCBI Gene Expression Omnibus (GEO). A total of 250 differentially expressed genes (DEGs) were investigated and analyzed using GEO2R, gene ontology (GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) identification. The GEO2R analysis revealed that TRPC6 was the sixth most highly expressed gene in patients with COPD. The GO analysis indicated that the upregulated DEGs were mainly concentrated in the plasma membrane, transcription, and DNA binding. The KEGG pathway analysis indicated that the upregulated DEGs were mainly involved in pathways related to cancer and axon guidance. TRPC6, one of the most abundant genes among the top 10 differentially expressed total RNAs (fold change ≥ 1.5) between the COPD and normal groups, was selected as a novel COPD biomarker based on the results of the GEO dataset and analysis using machine learning models. The upregulation of TRPC6 was verified in PM-stimulated RAW264.7 cells, which mimicked COPD conditions, compared to untreated RAW264.7 cells by a quantitative reverse transcription polymerase chain reaction. In conclusion, our study suggests that TRPC6 can be regarded as a potential novel biomarker for COPD pathogenesis.

Designer nanorings with functional cavities from self-assembling ß-sheet peptides.

ß-Barrel proteins that take the shape of a ring are common in many types of water-soluble enzymes and water-insoluble transmembrane pore-forming proteins. Since ß-barrel proteins perform diverse functions in the cell, it would be a great step towards developing artificial proteins if we can control the polarity of artificial ß-barrel proteins at will. Here, we describe a rational approach to construct ß-barrel protein mimics from the self-assembly of peptide-based building blocks. With this approach, the direction of the self-assembly process toward the formation of water-soluble ß-barrel nanorings or water-insoluble transmembrane ß-barrel pores could be controlled by the simple but versatile molecular manipulation of supramolecular building blocks. This study not only delineates the basic driving force that underlies the folding of ß-barrel proteins, but also lays the foundation for the facile fabrication of ß-barrel protein mimics, which can be developed as nanoreactors, ion- and small-molecule-selective pores, and novel antibiotics.

Self-assembly of a peptide rod-coil: a polyproline rod and a cell-penetrating peptide Tat coil.

Peptide rod-coil molecules, composed of a stiff polyproline rod and a hydrophilic cell-penetrating peptide Tat coil, self-assemble into nanocapsules and mediate efficient intracellular delivery of entrapped hydrophilic molecules.

Tunable bacterial agglutination and motility inhibition by self-assembled glyco-nanoribbons.

We explored a method of controlling bacterial motility and agglutination by using self-assembled carbohydrate-coated beta-sheet nanoribbons. To this aim, we synthesized triblock peptides that consist of a carbohydrate, a polyethylene glycol (PEG) spacer, and a beta-sheet-forming peptide. An investigation into the effect of PEG-spacer length on the self-assembly of the triblock peptides showed that the PEG should be of sufficiently length to stabilize the beta-sheet nanoribbon structure. It was found that the stabilization of the nanoribbon led to stronger activity in bacterial motility inhibition and agglutination, thus suggesting that antibacterial activity can be controlled by the stabilization strategy. Furthermore, another level of control over bacterial motility and agglutination was attained by co-assembly of bacteria-specific and -nonspecific supramolecular building blocks. The nanoribbon specifically detected bacteria after the encapsulation of a fluorescent probe. Moreover, the detection sensitivity was enhanced by the formation of bacterial clusters. All these results suggest that the carbohydrate-coated beta-sheet nanoribbons can be developed as promising agents for pathogen capture, inactivation, and detection, and that the activity can be controlled at will.