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Mutations in ABCA3 can result in surfactant deficiency, leading to respiratory distress syndrome in term neonates, and interstitial lung disease (ILD) in children. Here, we report an extremely rare case of ILD in an identical twin with novel ABCA3 germline mutations. Interestingly, they showed mostly similar, but slightly different, clinical features. Our cases suggest that, in addition to genetic factors, non-genetic factors are involved in the severity of the disease and its clinical course. Studies of gene-environment interactions, especially with twins, are needed, as they may contribute to the understanding of the clinical heterogeneity of ILD and its  association with various underlying conditions as well as rare variant mutations.

The leaves and branches of rabbiteye blueberry are rich in proanthocyanidins, which are thought to have different physiological activities depending on their structure and degree of polymerization. In this study, we analyzed the constituents of the leaves and branches of rabbiteye blueberry to determine the seasonal variations in polyphenol and proanthocyanidin (PAC) contents as well as their mean degrees of polymerization (mDP). Total PAC content was determined using two methods: The p-dimethylaminocinnamaldehyde (DMACA) method, which measures monomeric PAC, showed an increase from spring to summer in both leaves and branches. On the other hand, using the butanol/HCl method, which measures only polymerized PAC, the PAC content of leaves increased from spring to summer but those of branches remained low throughout the year, showing no significant increase or decrease. Furthermore, analysis of the mDP of PAC showed increases from spring to summer in the leaves of 'Kunisato 35 gou'. Although the highest value (8.0) was observed in October, values around 4 remained throughout the year in the branches. Since differences in polymerization degree affect absorption in the body and physiological properties such as antioxidant capacity, selecting the appropriate harvest time and plant organs for each purpose is expected to ensure the quality of processed blueberry foods.

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism.

Interstitial lung disease (ILD) represents a large group of diseases characterized by chronic inflammation and fibrosis of the lungs, for which therapeutic options are limited. Among several causative genes of familial ILD with autosomal dominant inheritance, the mutations in the BRICHOS domain of SFTPC cause protein accumulation and endoplasmic reticulum stress by misfolding its proprotein. Through a screening system using these two phenotypes in HEK293 cells and evaluation using alveolar epithelial type 2 (AT2) cells differentiated from patient-derived induced pluripotent stem cells (iPSCs), we identified Cryptotanshinone (CPT) as a potential therapeutic agent for ILD. CPT decreased cell death induced by mutant SFTPC overexpression in A549 and HEK293 cells and ameliorated the bleomycin-induced contraction of the matrix in fibroblast-dependent alveolar organoids derived from iPSCs with SFTPC mutation. CPT and this screening strategy can apply to abnormal protein-folding-associated ILD and other protein-misfolding diseases., Competing Interests: Y.Y., S.G., and M.Ha. are founders and shareholders of HiLung Inc. Y.Y. is a representative director of the board and S.G. is an external board member of HiLung Inc. Y.Y. and S.G. filed the patents related to the methods of generating iPSC-derived AEC in this study: WO2014168264A1 and WO2016143803A1., (© 2023 The Authors.)

The storage roots of purple-fleshed sweet potato contain a variety of anthocyanins and polyphenols. Little is known about changes in the total content and composition of anthocyanins and polyphenols in the early growth stages of the root system. In this study, we investigated the changes in anthocyanins and polyphenols in the root system of purple-fleshed sweet potato cultivars at 15, 30, 45, and 60 days after transplant (DAT). Unexpectedly, the highest percentage of acylated anthocyanins in three purple-fleshed cultivars among all growth stages was at 15 DAT. On the other hand, the total polyphenol content in the early growth stages of the root system increased rapidly toward 45 DAT, just before the beginning of storage root enlargement, and then decreased rapidly as the storage roots began to enlarge. These data indicate that the early growth stage of the root system is a critical time. This timing may present a strategy to maximize the accumulation of polyphenols with high antioxidant activity, as well as acylated anthocyanins, to protect against abiotic and biotic stresses.

Intravenous immunoglobulin (IVIg) has been used to treat inflammatory demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, and multifocal motor neuropathy. Despite studies demonstrating the clinical effectiveness of IVIg, the mechanisms underlying its effects remain to be elucidated in detail. Herein, we examined the effects of IVIg on lysolecithin-induced demyelination of the sciatic nerve in a mouse model. Mice -administered with IVIg 1 and 3 days post-injection (dpi) of lysolecithin -exhibited a significantly decreased demyelination area at 7 dpi. Immunoblotting analysis using two different preparations revealed that IVIg reacted with a 36-kDa membrane glycoprotein in the sciatic nerve. Subsequent analyses of peptide absorption identified the protein as a myelin protein in the peripheral nervous system (PNS) known as large myelin protein zero (L-MPZ). Moreover, injected IVIg penetrated the demyelinating lesion, leading to deposition on L-MPZ in the myelin debris. These results indicate that IVIg may modulate PNS demyelination, possibly by binding to L-MPZ on myelin debris.

The rotator cuff (RC) is frequently torn at the enthesis composed of fibrocartilage. We aimed to histopathologically evaluate lining layers and assess the distribution of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, and microRNA (miR)-140s in the synovia of patients with RC tears. We recruited 51 patients who underwent arthroscopic surgical treatment for full-thickness rotator cuff tears, including 26 patients with < 3 cm tear size (group N) and 25 patients with ≥ 3 cm tear size (group W). Biopsied synovia were analyzed using histological and immunohistological techniques for the presence ADAMTS4 and ADAMTS5. The layers of the synovial lining were morphologically classified into 3 grades according to the synovitis score and staining levels of ADAMTSs. The glenohumeral synovia from 8 patients with recurrent shoulder dislocation (group C) were used as controls. Furthermore, in situ hybridization was performed to evaluate the presence of miR-140s in patients with massive tears and recurrent shoulder dislocation. The staining levels were evaluated and analyzed based on comparison between patient groups and correlation between ADAMTS5 and miR-140s. Histological analysis revealed significant differences between groups W and C. ADAMTS5 and ADAMTS4 were strongly expressed in the synovial lining of patients in group W, and this expression was significantly higher than that in groups C and N. In addition, expression of ADAMTS5 was inversely correlated with that of miR-140-3p. This study showed that synovia from group W had a significantly higher rate of severely thickened areas with strong expression of both aggrecanases. Furthermore, the area with weak expression of miR-140-3p showed strong ADAMTS5 expression., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)