Aldehyde dehydrogenase 1a3 defines a subset of failing pancreatic β cells in diabetic mice

Insulin-producing β cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from β-cell dysfunction to β-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing β cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH+) as β cells become dedifferentiated. Flow-sorted ALDH+ islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis demonstrates that ALDH+ cells are characterized by: (i) impaired oxidative phosphorylation and mitochondrial complex I, IV and V; (ii) activated RICTOR; and (iii) progenitor cell markers. We propose that impaired mitochondrial function marks the progression from metabolic inflexibility to dedifferentiation in the natural history of β-cell failure

Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects against indomethacin-induced gastric cell damage in vivo and in vitro

Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse biological responses. Recently, we found that LPA ameliorates NSAIDs-induced gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for treatment of gastrointestinal (GI) disorders. We found that half of them contained LPA at relatively high levels (40–240 μg/g) compared to soybean seed powder (4.6 μg/g), which we previously identified as an LPA-rich food. The LPA in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid fraction that ameliorates indomethacin-induced gastric ulcer in mice. Synthetic 18:1 LPA, peony root LPA and peony root lipid enhanced prostaglandin E2 production in a gastric cancer cell line, MKN74 cells that express LPA2 abundantly. These materials also prevented indomethacin-induced cell death and stimulated the proliferation of MKN74 cells. We found that LPA was present in stomach fluids at 2.4 μM, which is an effective LPA concentration for inducing a cellular response in vitro. These results indicated that LPA is one of the active components of medicinal herbs for the treatment of GI disorder and that orally administered LPA-rich herbs may augment the protective actions of endogenous LPA on gastric mucosa

Estimating normal lung weight measurement using postmortem CT in forensic cases

Purpose: The aim of this study is to estimate the lung weight using postmortem CT in well aerated lung autopsy cases. The correlation coefficients to the lung weight were also evaluated for the cadavers' height, weight, whole body surface area (WBSA), body mass index, and estimated lung volume. Materials and methods: From October 2015 to July 2016, 31 cadavers (male 12, female 19, age 20-98 (mean 66.9) y.o., postmortem interval 0.3-75.0 (5.7) days) were compared as regards body weight, height, whole body surface area (WBSA), body mass index (BMI), lung volume on CT, and total lung volume classified into several CT number categories, with their lung weight in autopsy. Results: The lung weight (mean ± SE) was 284.9 ± 14.8 g in right lung and 249.3 ± 12.9 g in left lung. The %ALV was 79.9 ± 0.9 HU (mean ± standard error (SE)) in both lungs, 80.3 ± 1.3 HU in right lung, and 77.6 ± 2.0 HU in left lung. Using a simple linear regression test, there was no statistically significant correlation between the lung weight and the categories (R2: body height 0.234, weight 0.224, WBSA 0.309, BMI 0.046, lung volume 0.059). The volume for each individual CT density category showed no significant correlation, but the stepwise regression test yielded an excellent correlation coefficient (R2 = 0.840). Conclusion: The well aerated lung weight was 284.9 ± 14.8 g in right lung and 249.3 ± 12.9 g in left lung, and the postmortem CT could estimate the lung weight with high correlation coefficient