Efficacy of 1-kestose supplementation in patients with mild to moderate ulcerative colitis: A randomised, double-blind, placebo-controlled pilot study.

BACKGROUND: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1-kestose is effective for active ulcerative colitis remains controversial. AIMS: This randomised, double-blind, placebo-controlled pilot trial investigated the efficacy of 1-kestose against active ulcerative colitis. METHODS: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1-kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. RESULTS: The clinical activity index at week 8 was significantly lower in the 1-kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1-kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha-diversity in the 1-kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short-chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups. DISCUSSION: Oral 1-kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome.

Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01).

OBJECTIVE: Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified. SUMMARY OF BACKGROUND DATA: Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial. METHODS: Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate. RESULTS: Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups. CONCLUSIONS: These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis.

Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition.

Branched-chain amino acids (BCAAs) are essential amino acids for mammals and play key roles in the regulation of protein metabolism. However, the effect of BCAA deficiency on protein metabolism in skeletal muscle in vivo remains unclear. Here we generated mice with lower BCAA concentrations by specifically accelerating BCAA catabolism in skeletal muscle and heart (BDK-mKO mice). The mice appeared to be healthy without any obvious defects when fed a protein-rich diet; however, bolus ingestion of BCAAs showed that mTORC1 sensitivity in skeletal muscle was enhanced in BDK-mKO mice compared to the corresponding control mice. When these mice were fed a low protein diet, the concentration of myofibrillar protein was significantly decreased (but not soluble protein) and mTORC1 activity was reduced without significant change in autophagy. BCAA supplementation in drinking water attenuated the decreases in myofibrillar protein levels and mTORC1 activity. These results suggest that BCAAs are essential for maintaining myofibrillar proteins during protein undernutrition by keeping mTORC1 activity rather than by inhibiting autophagy and translation. This is the first report to reveal the importance of BCAAs for protein metabolism of skeletal muscle in vivo.

New direction for environmental water management.

Japan experienced severe environmental problems including water pollution and damages to aquatic organisms and fishery industry through and after the high economic growth period in the 1960s. One of the countermeasures to address these problems was the Total Pollutant Load Control System (TPLCS), which has been implemented with the aim of reducing the total amount of pollutant loads, specifically targeting Chemical Oxygen Demand (COD), total nitrogen and total phosphorus. The TPLCS has significantly improved the quality of the coastal sea water. However, while the accumulated pollutant loads from the past industrialization have still remained, new environmental concerns have arisen. Our new environmental policies are thus to deal with conservation of biological diversity and other related marine environmental issues. Japan has entered a new phase of environmental management, setting the new direction and framework toward a beautiful, bio-diverse, bustling-with-people and bountiful sea.