National Institute of Health Sciences

The number of authorized genetically modified (GM) soybeans has increased worldwide. In Japan, 34 GM soybeans containing single events and their stacked varieties have been approved as food. However, not all approved GM events are commercially cultivated or distributed. In this study, we evaluated domestically distributed samples from the United States (US) and Canada using 17 event-specific detection methods for GM soybeans. Identity-preserved (IP) soybean samples imported from the US and Canada, and non-IP samples from the US in 2021 and 2022 were analyzed. Four GM soybean events consisting of MON89788, A5547-127, MON87708, and DAS-44406 were detected in all lots in the non-IP samples. Furthermore, a single-kernel-based analysis was conducted to determine whether the detected GM soybean events are stacked. The results suggest that DAS-44406 is rapidly increasing, particularly as a single event among GM soybeans.

A comprehensive analysis of metabolites (metabolomics) has been proposed as a new strategy for analyzing liquid biopsies and has been applied to identify biomarkers predicting clinical responses or adverse events associated with specific treatments. Here, we aimed to identify metabolites associated with bortezomib (Btz)-related toxicities and response to treatment in newly diagnosed multiple myeloma (MM).

Fifty-four plasma samples from transplant-ineligible MM patients enrolled in a randomized phase II study comparing two less-intensive regimens of melphalan, prednisolone and Btz (MPB) were subjected to the lipidomic profiling analysis. The amount of each lipid metabolite in plasma obtained prior to MPB therapy was compared to toxicity grades and responses to MPB therapy.

High levels of 7 phospholipids (4 lysophosphatidylcholines and 3 phosphatidylcholines) were observed in cases with Btz-induced ≥ grade 2 peripheral neuropathy (BiPN) (n = 11). In addition, low levels of 3 fatty acids (FAs)-FA (18:2), FA (18:1), and FA (22:6)-were observed in patients who developed severe skin disorders ≥ grade 2 (n = 10). No metabolite significantly associated with treatment response was identified.

We conclude that levels of specific plasma lipid metabolites are associated with the severity of BiPN and skin disorders in patients with MM. These metabolites may serve as candidate biomarkers to predict Btz-induced toxicity in patients with MM before initiating Btz-containing therapy.

Toxicological information on moniliformin (MON), an emerging mycotoxin, is limited. This study examined the acute and 28-day toxicity of orally administered MON in male ICR mice. Regarding the acute toxicity, among single oral doses of 0, 20, 40, and 80 mg/kg body weight (BW), MON caused proximal tubular necrosis in the kidneys at ≥ 40 mg/kg BW, and the lethal dose 50 value was estimated as 68.1 mg/kg BW. Regarding the 28-day toxicity, among oral doses of 0, 10, 20, and 40 mg/kg BW/day, MON increased absolute heart weight at 40 mg/kg BW, but histopathological changes were not evident in the heart. In contrast, 40 mg/kg BW MON induced centrilobular liver cell hypertrophy accompanied by increased absolute liver weight. Moreover, MON dose-dependently increased the absolute kidney weight at ≥ 20 mg/kg BW and increased the incidence of renal tubular regeneration at 40 mg/kg BW. RNA sequencing analysis in the renal cortex after a single dose of 40 mg/kg BW MON revealed upregulation of metabolic response-related genes, such as Cyp3a13, Cyp26b1, and Cyp4f15, and oxidative stress-related Gpx7. These results suggest that MON targets the kidneys in mice. Orally ingested MON may be metabolized in the kidneys as well as in the liver, and active intermediates or reactive oxygen species may induce renal tubular toxicity, causing proximal tubular necrosis. Based on kidney changes, the no-observed-adverse-effect-level of MON in the 28-day oral toxicity study of male mice was determined to be 10 mg/kg BW/day.