Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA.

Folic acid, served as dietary supplement, is closely linked to one-carbon metabolism and methionine metabolism. Previous clinical evidence indicated that folic acid supplementation displays dual effect on cancer development, promoting or suppressing tumor formation and progression. However, the underlying mechanism remains to be uncovered. Here, we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma (HCC) induced by DEN/high-fat diet (HFD), simultaneously with increased expression of methionine adenosyltransferase 2A (gene name, MAT2A; protein name, MATIIα), the key enzyme in methionine metabolism, and acceleration of methionine cycle in cancer tissues. In contrast, folate-free diet reduces MATIIα expression and impedes HFD-induced HCC development. Notably, methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein (VCIP135) which functions as a deubiquitylating enzyme to bind and stabilize MATIIα in response to folic acid signal. Consistently, upregulation of MATIIα expression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent tissues. Furthermore, liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC, demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on Mat2a. Moreover, folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a deletion. Together, folate promotes the integration of methionine and one-carbon metabolism, contributing to HCC development via hijacking MATIIα metabolic pathway. This study provides insight into folate-promoted cancer development, strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIα expression.

Transcriptome Analysis Reveals the Effects of Chinese Chive (Allium tuberosum R.) Extract on Fusarium oxysporum f. sp. radicis-lycopersici Spore Germination.

Fusarium oxysporum f. sp. radicis-lycopersici (Forl) causes Fusarium crown and root rot of tomato, leading to severe yield losses. Chinese chive and the Chinese chive extract reportedly have antifungal effects. In this study, Chinese chive extract treatments inhibited Forl spore germination, with an EC50 of 0.40 g ml-1 in vitro. Furthermore, the mechanism underlying the fungicidal effects of the Chinese chive extract was analyzed by RNA sequencing. A total of 1252 differentially expressed genes (DEGs) were detected, of which 396 were upregulated and 856 were downregulated. The DEGs were related to starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, galactose metabolism, fatty acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, peroxisomes, ribosome biogenesis in eukaryotes, mismatch repair, and the phosphatidylinositol signaling system, implying these pathways contribute to the fungicidal activity of the Chinese chive extract. The qRT-PCR results verified the accuracy of the RNA sequencing data. Thus, the Chinese chive extract can inhibit Forl spore germination by affecting spore nutrient metabolism.

Effects of early parenteral iron combined erythropoietin in preterm infants: A randomized controlled trial.

BACKGROUD: The aim of the study was to evaluate the effect of early parenteral iron supplementation combined erythropoietin for prevention of anemia in preterm infants. METHODS: In total, 96 preterm infants were randomly assigned to 3 groups: a control group receiving standard parenteral nutrition (group 1: n = 31), an iron-supplemented group (group 2: IS, n = 33), and an iron-supplemented combined erythropoietin group (group 3: IS+EPO, n = 32). The primary objective was to assess hemoglobin (Hb) levels. The secondary objectives included assessment of red blood cell counts (RBC), mean cell volume (MCV), serum iron, ferritin, percentages of reticulocyte (RET), total iron binding capacity (TIBC) and oxidative stress, which was assessed by measuring plasma levels of malondialdehyde and superoxide dismutase at baseline and at 2 weeks. The blood routine indices including Hb, RBC, MCV, and percentages of RET were measured at corrected age of 1 and 3 months. RESULTS: At 2 weeks of life, the percentages of reticulocyte in group 2 and group 3 were significantly higher than those in group 1 (2.1±0.4, 2.5±0.3, and 1.7±0.3, respectively, P < 0.001, P<0.001), whereas TIBC were significantly lower than those in group 1 (36.7±4.6, 36.0±4.7, and 41.6 ±â€Š5.2 respectively, P = 0.011, P = 0.006). There were no significant differences in RBC counts, the levels of hemoglobin, ferritin, malondialdehyde, and superoxide dismutase among the 3 groups at 2weeks of life. RBC, Hb, MCV, body weight, body length, and head circumference at a corrected age of 1 month did not differ among 3 groups. At corrected age of 3months, more infants in the control group had abnormal Hb and MCV levels (Hb levels: 114.3 ±â€Š21.3, 123.7 ±â€Š31.6, and 125.1 ±â€Š21.2, P = 0.021, P = 0.034, respectively; MCV: 74.1 ±â€Š3.5, 78.3 ±â€Š4.7 and 79.1 ±â€Š5.2, P = 0.017, P = 0.012, respectively), whereas cases of oral iron, cases of breastfeeding, RBC, body weight, body length, and head circumference were not different among 3 groups. CONCLUSION: Early parenteral iron supplementation combined erythropoietin in preterm infants improved the percentages of reticulocyte, decreased total iron binding capacity, and improved the Hb and MCV levels at 3 months of age. Early parenteral iron supplementations with EPO were beneficial for the preterm infants.