ABSTRACT
SCOPE: The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of α-linolenic acid (ALA) has seldom been reported. METHODS AND RESULTS: After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5 g kg-1 ) promotes small intestinal and villus growth by activating the Wnt/ß-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation. CONCLUSION: These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/ß-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.
Subject(s)
Intestines , alpha-Linolenic Acid , Animals , Cell Proliferation , Fatty Acids, Volatile/metabolism , Intestinal Mucosa/metabolism , Mice , Stem Cells/physiology , alpha-Linolenic Acid/metabolism , alpha-Linolenic Acid/pharmacologyABSTRACT
OBJECTIVE: To investigate the expression of cyclin A protein in childhood acute leukemia (AL) and its significance. METHODS: By using Western blotting analysis, cyclin A protein in bone marrow mononuclear cells from 47 newly diagnosed AL children and 33 non-hematological malignancy children was detected. RESULTS: The expression of cyclin A in AL group (0.38 +/- 0.20) was higher than that in control group (0.03 +/- 0.15) (P < 0.01). The expression of cyclin A in high risk acute lymphocyte leukemia (ALL) group (HR-ALL) (0.62 +/- 0.38) was higher than that in standard risk ALL group (SR-ALL) (0.33 +/- 0.33) (P < 0.05). The expression of cyclin A in WBC > or = 50 x 10(9)/L group and in WBC < 50 x 10(9)/L group was (0.64 +/- 0.36) and (0.39 +/- 0.38), respectively (P < 0.05). Eight (44.4%) out of 18 patients with positive cyclin A expression achieved complete remission (CR). The CR rate was lower than that of patients with negative cyclin A expression (100%) (P < 0.01). CONCLUSIONS: The higher expression of cyclin A may predict a poor prognosis for childhood ALL.
