Detailed understanding of the pathogenesis and development of effective therapies for pulmonary fibrosis (PF) have been hampered by lack of in vitro human models that recapitulate disease pathophysiology. In this study, we generated alveolar organoids (AOs) derived from human pluripotent stem cells (hPSCs) for use as an PF model and for drug efficacy evaluation. Stepwise direct differentiation of hPSCs into alveolar epithelial cells by mimicking developmental cues in a temporally controlled manner was used to generate multicellular AOs. Derived AOs contained the expected spectrum of differentiated cells, including alveolar progenitors, type 1 and 2 alveolar epithelial cells and mesenchymal cells. Treatment with transforming growth factor (TGF-β1) induced fibrotic changes in AOs, offering a PF model for therapeutic evaluation of a structurally truncated form (NP-011) of milk fat globule-EGF factor 8 (MFG-E8) protein. The significant fibrogenic responses and collagen accumulation that were induced by treatment with TGF-β1 in these AOs were effectively ameliorated by treatment with NP-011 via suppression of extracellular signal-regulated kinase (ERK) signaling. Furthermore, administration of NP-011 reversed bleomycin-induced lung fibrosis in mice also via ERK signaling suppression and collagen reduction. This anti-fibrotic effect mirrored that following Pirfenidone and Nintedanib administration. Furthermore, NP-011 interacted with macrophages, which accelerated the collagen uptake for eliminating accumulated collagen in fibrotic lung tissues. This study provides a robust in vitro human organoid system for modeling PF and assessing anti-fibrotic mechanisms of potential drugs and suggests that modified MGF-E8 protein has therapeutic potential for treating PF.

Aromadendrin, a flavonol, has been reported to possess a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-diabetic properties. However, the underlying mechanism by which aromadendrin exerts its biological activity has not been extensively demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of aromadedrin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Aromadendrin significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2. In accordance, aromadendrin attenuated LPSinduced overexpression iNOS and COX-2. In addition, aromadendrin significantly suppressed LPS-induced degradation of IκB, which sequesters NF-κB in cytoplasm, consequently inhibiting the nuclear translocation of pro-inflammatory transcription factor NF- κB. To elucidate the underlying signaling mechanism of anti-inflammatory activity of aromadendrin, MAPK signaling pathway was examined. Aromadendrin significantly attenuated LPS-induced activation of JNK, but not ERK and p38, in a concentration-dependent manner. Taken together, the present study clearly demonstrates that aromadendrin exhibits anti-inflammatory activity through the suppression of nuclear translocation of NF-κB and phosphorylation of JNK in LPS-stimulated RAW 264.7 macrophage cells.

The complete mitochondrial genome of a Korean Ussurian tube-nosed bat, Murina ussuriensis, was determined. The mitochondrial genome of M. ussuriensis is 17,285 bp in length with a total base composition of 33.8% A, 28.9% T, 23.8% C, and 13.4% G. All the protein-coding genes (total length of 11,401 bp) were encoded in H-strand except for ND6 in L-strand. The total length of 22 tRNA genes was 1516 bp varying from 62 bp (tRNA (Ser) ((AGY))) to 74 bp (tRNA (Leu) ((UUR)) and tRNA (Gln)). The 12S rRNA and 16S rRNA genes were 972 and 1558 bp in length, respectively. The D-loop region was 2496 bp in length.

We characterized the complete mitogenome of Pipistrellus coromandra (Indian pipistrelle) for comparative analysis of mitogenomes and for resolving the phylogenetic relationship of four tribes in the subfamily Vespertilioninae. The mitogenome size of P. coromandra was 17,153 bp, with a control region and a typical set of 37 mitochondrial genes. The nucleotide composition of the P. coromandra mitogenome showed an AT bias with a nucleotide composition of 33.5% A, 30.7% T, 13.3% G, and 22.5% C. The mitochondrial protein-coding genes in P. coromandra use the standard start codon (ATN), two stop codons (TAA and AGA), and two incomplete stop codons (TA-and T-). The intertribal relationship of four tribes was highly resolved from the phylogenetic analysis of mitogenome sequences.

There are two subspecies of Rhinolophus ferrumequinum currently recognized in South Korea. The Korean greater horseshoe bat subspecies, Rhinolophus ferrumequinum quelpartis, is distributed only in Jeju Island. The complete mitochondrial genome of the island subspecies was determined and revealed 99.7% similarity to the mainland subspecies Rhinolophus ferrumequinum korai. If d-loop region is excluded, similarity of the two genomes was 99.9%.