Nintedanib exerts anti-pulmonary fibrosis activity via inhibiting TANK-binding kinase 1 (TBK1) phosphorylation

We described a chemoproteomics approach to identify TBK1 as a key target of the multikinase inhibitor nintedanib in IPF. This insight may facilitate a better understanding of the functional mechanism of nintedanib for antifibrosis efficacy.

Synovial mesenchymal stem cell-derived exosomal miR-320c enhances chondrogenesis by targeting ADAM19

Background: Synovial mesenchymal stem cell (SMSC)-derived exosomes show treatment potential in osteoarthritis, although their functional mechanism is still unclear. Materials & methods: Osteoarthritis chondrocytes and normal SMSC were cultured. Subsequently, chondrocytes were co-cultured with SMSC or miR-320c-overexpressing SMSC-derived exosomes, or directly transfected with miR-320c mimic. Furthermore, compensate experiments were conducted. Results: SMSC promoted chondrocyte proliferation, migration, COL2A1 and ACAN expressions while suppressing apoptosis by transmitting exosomes. Furthermore, miR-320c-overexpressing SMSC-derived exosomes and direct miR-320c overexpression in chondrocytes presented more significant effect on enhancing chondrogenesis. In addition, miR-320c directly targeted ADAM19, and ADAM19 overexpression compensated the regulation of miR-320c on chondrogenesis. Conclusion: SMSC-derived exosomal miR-320c enhances chondrogenesis through targeting ADAM19, highlighting a potentially novel mechanism of SMSC in treating osteoarthritis.

Possible effect of alkalization therapy on SARS-CoV-2 virus lifecycle

This proposal tries to drive attention to the observation that pH variation plays a fundamental role in the functional mechanism of SARS-CoV-2 virus proteases. Depending on this role, testing the effect of alkalization therapy on the SARS-CoV-2 patients could be reasonable.

A Novel circRNA–miRNA–mRNA Hub Regulatory Network in Lung Adenocarcinoma

The growing evidence suggests that circular RNAs (circRNAs) have significant associations with tumor occurrence and progression, yet the regulatory mechanism of circRNAs in lung adenocarcinoma (LUAD) remains unclear. This study clarified the potentially regulatory network and functional mechanism of circRNAs in LUAD. The expression data of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were obtained from the Gene Expression Omnibus (GEO) database. Relying on GSE101586, GSE101684, and GSE112214, we identified differentially expressed circRNAs (DEcircRNAs). Depending on GSE135918 and GSE32863, we screened out differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs), respectively. Then, a novel competing endogenous RNA (ceRNA) regulatory network related to LUAD was constructed. We also revealed biological processes and signal pathways regulated by these DEcircRNAs. Based on gene expression data and survival information of LUAD patients in The Cancer Genome Atlas (TCGA) and GEO, we implemented survival analysis to select DEmRNAs related to prognosis and build a novel circRNA–miRNA–mRNA hub regulatory network. Meanwhile, quantitative real-time PCR (qRT-PCR) was utilized to validate DEcircRNAs in the ceRNA hub regulatory network. As a result, a total of 8 DEcircRNAs, 19 DEmiRNAs, and 85 DEmRNAs were identified. The novel ceRNA regulatory network included 5 circRNAs, 8 miRNAs, and 22 mRNAs. The final ceRNA hub regulatory network contained two circRNAs, two miRNAs, and two mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the five DEcircRNAs may affect LUAD onset and progression through Wnt signaling pathway and Hippo signaling pathway. All in all, this study revealed the regulatory network and functional mechanism of circRNA-related ceRNAs in LUAD.

Functional Mechanism of Proton Pump-Type Rhodopsins Found in Various Microorganisms as a Potential Effective Tool in Optogenetics

Microbial rhodopsins, which are photoreceptive membrane proteins consisting of seven α-helical structural apoproteins (opsin) and a covalently attached retinal chromophore, are one of the most frequently used optogenetic tools. Since the first success of neuronal activation by channelrhodopsin, various microbial rhodopsins functioning as ion channels or pumps have been applied to optogenetics. The use of light-driven ion pumps to generate large negative membrane potentials allows the silencing of neural activity. Although anion-conductive channelrhodopsins have been recently discovered, light-driven outward H+-pumping rhodopsins, which can generate a larger photoinduced current than a light-driven inward Cl−-pump halorhodopsin, must be more efficient tools for this purpose and have been often utilized for optogenetics. There are abundant proton pumps in the microbial world, providing numerous candidates for potential practical optogenetic instruments. In addition, their distinctive features (that is, being accompanied by photoinduced intracellular pH changes) could enable expansion of this technique to versatile applications. Thus, intensive investigation of the molecular mechanisms of various microbial H+-pumps may be useful for the exploration of more potent tools and the creation of effectively designed mutants. In this chapter, we focus on the functional mechanism of microbial H+-pumping rhodopsins. Further, we describe the future prospects of these rhodopsins for optogenetic applications.