Positional differences of intronic transposons in pAMT affect the pungency level in chili pepper through altered splicing efficiency

トウガラシの辛味レベルを変化させる遺伝子変異を発見 －激辛・中辛・辛くないを作り分ける－. 京都大学プレスリリース. 2019-08-30.Capsaicinoids are unique compounds that give chili pepper fruits their pungent taste. Capsaicinoid levels vary widely among pungent cultivars, ranging from low‐pungency to extremely pungent. However, the molecular mechanisms underlying its quantitative variation have not been elucidated. Our previous study identified various loss‐of‐function alleles of the pAMT gene, which led to low‐pungency. The mutations in these alleles are commonly defined by Tcc transposon insertion and its footprint. In this study, we identified two leaky pamt alleles (pamtL1 and pamtL2) with different levels of pAMT activity. Notably, both alleles had a Tcc transposon insertion in intron 3, but the locations of the insertions within the intron were different. Genetic analysis revealed that pamtL1, pamtL2 and a loss‐of‐function pamt allele reduced capsaicinoid levels to about 50%, 10%, and less than 1%, respectively. pamtL1 and pamtL2 encoded functional pAMT proteins, but they exhibited lower transcript levels compared with the functional‐type. RNA‐seq analysis showed that intronic transposons disrupted splicing in intron 3, which resulted in simultaneous expression of functional pAMT mRNA and non‐functional splice variants containing partial sequences of Tcc. The non‐functional splice variants were more dominant in pamtL2 than that in pamtL1. This suggested that the difference in position of the intronic transposons could alter splicing efficiency, which led to different pAMT activities and reduced capsaicinoid content to different levels. Our results provide a striking example where intronic transposons caused allelic variations, which contributed to quantitative differences in secondary metabolite contents

Cost-effectiveness of adding a Helicobacter pylori antibody test to the upper gastrointestinal series in gastric cancer screening at the workplace

Objective: Helicobacter pylori infections increase gastric cancer risk. Detecting and eradicating Helicobacter pylori infections and implementing a follow-up strategy should be considered by occupational health practitioners. This study aimed to evaluate the cost-effectiveness of adding an H. pylori antibody (HPA) test to current gastric cancer screening using upper gastrointestinal series (UGI) at the workplace in Japan. Methods: The data of Japanese people aged ≥40 years were collected from PubMed and evaluated in two cohorts: UGI (X-ray examination)+HPA test and UGI only. A Markov model was used for the cost-effectiveness analysis of the UGI+HPA test and UGI-only cohorts. The main outcomes were cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The impact of uncertainty was assessed using one-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA). Results: A base-case analysis showed that the UGI+HPA test strategy was less costly (−US＄1,039 and −US＄1,496) and more effective (0.415 and 0.437 QALYs) than the UGI-only strategy in the 40- and 50-year-old groups, respectively. The UGI+HPA test strategy was assessed as a dominant strategy. In the OWSA, the tornado diagram showed negative expected costs and positive QALY gains within the established ranges for all parameters. In the PSA, more than 95% of the simulations demonstrated ICER <5 million yen (US＄51,674; US＄1=96.76 yen)/QALY. Conclusions: This modeling study suggests that gastric cancer screening using UGI+HPA test followed by eradication and annual opportunistic screening, compared with UGI only, resulted in lower costs and greater QALY gains for both 40- and 50-year-old groups at the workplace

The Biological Efficacy of Natural Products against Acute and Chronic Inflammatory Diseases in the Oral Region

The oral inflammatory diseases are divided into two types: acute and chronic inflammatory diseases. In this review, we summarize the biological efficacy of herbal medicine, natural products, and their active ingredients against acute and chronic inflammatory diseases in the oral region, especially stomatitis and periodontitis. We review the effects of herbal medicines and a biscoclaurin alkaloid preparation, cepharamthin, as a therapy against stomatitis, an acute inflammatory disease. We also summarize the effects of herbal medicines and natural products against periodontitis, a chronic inflammatory disease, and one of its clinical conditions, alveolar bone resorption. Recent studies show that several herbal medicines such as kakkonto and ninjinto reduce LPS-induced PGE 2 production by human gingival fibroblasts. Among herbs constituting these herbal medicines, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly reduce PGE 2 production. Moreover, anti-osteoclast activity has been observed in some natural products with anti-inflammatory effects used against rheumatoid arthritis such as carotenoids, flavonoids, limonoids, and polyphenols. These herbal medicines and natural products could be useful for treating oral inflammatory diseases

Spermine Suppresses Adipocyte Differentiation and Exerts Anti-Obesity Effects In Vitro and In Vivo

Endogenous polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm) affect adipocyte differentiation. In this study, we investigated the effect of exogenously supplemented polyamines on mouse adipocyte differentiation and anti-obesity actions in vitro and in vivo. The preadipocyte cell line, 3T3-L1, was cultured with Put, Spd, or Spm, and lipid accumulation in the cells was measured by Oil Red O staining. Lipid accumulation was significantly suppressed by Spm. Suppression of CCAAT/enhancer binding protein α mRNA by Spm suggested that the decreased lipid accumulation was due to delaying the cell differentiation. The body weight and fat of obese mice induced with a high-fat diet were reduced by oral ingestion of Spm. In conclusion, oral supplementation of Spm has the ability to prevent obesity through inhibition of adipocyte differentiation