Comparative transcriptomic analysis reveals the regulatory effects of inorganic nitrogen on the biosynthesis of Monascus pigments and citrinin.

Monascus spp. and its secondary metabolites have been widely applied in foods and medicines for thousands of years in eastern Asia. Nitrogen sources are essential nutrients for the growth and metabolism of Monascus spp. Our previous study found that inorganic nitrogen sources (especially NH4Cl and NH4NO3) promoted the biosynthesis of Monascus pigments (MPs) and inhibited the production of citrinin. The objective of the present study was to investigate the regulatory mechanism of inorganic nitrogen on the biosynthesis of MPs and citrinin by the comparative transcriptional approach (RNA sequencing combined with RT-qPCR). Results indicated that the submerged fermentation of M. purpureus M3103 with NH4Cl or NH4NO3 as the sole nitrogen source can significantly increase the yields of MPs (especially for Monascus orange and red pigments) and decrease citrinin production, compared with the organic nitrogen source (peptone group). Comparative transcriptomic profiling by RNA sequencing found that the numbers of differentially expressed genes (DEGs) between different experimental groups-M group (peptone group) vs. ML group (NH4Cl group), and M group (peptone group) vs. MX group (NH4NO3 group), were 722 and 1287, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that genes involved in carbon and nitrogen metabolism, biosynthesis of amino acids were up-regulated by NH4Cl and NH4NO3, which would produce more biosynthetic precursors for MPs. Whereas, the inorganic nitrogen source (both of NH4Cl and NH4NO3) down-regulated the expression levels of genes involved in tyrosine metabolism. In addition, NR analysis indicated that the essential genes and transcription factors involved in the biosynthesis pathway of citrinin were down-regulated by NH4Cl and NH4NO3. These results indicated that NH4Cl or NH4NO3 as a nitrogen source for M. purpureus M3103 can significantly promote the precursor synthesis of Monascus pigments, but reduce the transcription of polyketide synthase for citrinin, and therefore significantly increase Monascus pigments production and decrease citrinin formation. These findings will facilitate a comprehensive understanding of the regulatory mechanisms of inorganic nitrogen in the biosynthesis of secondary metabolites in M. purpureus, and would benefit the application of M. purpureus in the production of MPs.

Modified-Nutrition Index is a Significant Prognostic Factor for the Overall Survival of the Nasopharyngeal Carcinoma Patients who Undergo Intensity-modulated Radiotherapy.

PURPOSE: To explore whether the modified-nutrition index (m-NI) is a prognostic factor for the overall survival (OS) in nasopharyngeal carcinoma (NPC) patients who undergo intensity-modulated radiotherapy (IMRT). METHODS: Clinical data were prospectively collected from NPC patients who underwent IMRT at our hospital between October 2008 and December 2014. The patient nutritional status before radiotherapy was evaluated using the m-NI, based on eight nutrition indicators including body mass index, arm muscle circumference, albumin, total lymphocyte count, red blood cell count, hemoglobin, serum pre-albumin, and transferrin. The independent prognostic value of m-NI for the OS was evaluated. RESULTS: A total of 323 patients (229 males, 94 females) were included in this study, and the follow-up rate was 99.7% (322/323). The 1-, 3-, and 5-yr OS rates between malnutrition and normal nutrition groups by using the m-NI were 93.0% vs. 96.9%, 76.4% vs. 82.8%, and 61.8% vs. 77.1%, respectively. A regression analysis showed that the m-NI was the significant prognostic value for the OS in NPC. CONCLUSIONS: The m-NI before radiotherapy is a significant prognostic factor for the OS in NPC patients. Further validation of our instrument is needed in other NPC patients.

Effect of chemoradiotherapy on nutrition status of patients with nasopharyngeal cancer.

We aimed to assess the effect of chemoradiotherapy on the nutritional status of patients with nasopharyngeal cancer (NPC) and to detect the risk factors for poor nutrition status in NPC patients after radiotherapy. A total of 104 NPC patients participated in this clinical observational study. Psychological distress and nutritional indicators were measured prior to chemoradiotherapy. During the course of radiation therapy, side effect symptoms were assessed weekly. At the end of radiotherapy, nutritional indicators were measured again. Logistic regression was used to identify the risk factors for poor nutritional status after radiotherapy. The values of the 9 nutritional indicators were significantly lower after radiotherapy (P < 0.001) than the initial values before treatment. After radiotherapy, 20.19% of patients had more than 10% weight loss. At a significance level of α = 0.05, the risk factors for poor nutritional status were old age (P = 0.042), female gender (P < 0.001), late stage of the disease (P = 0.013), depression (P = 0.024), high side effect score (P = 0.007), and moderate nutritional status before radiotherapy (P = 0.015). Radiotherapy affects the nutritional status of NPC patients. To prevent malnutrition during radiotherapy, nutritional assessment and intervention should be an integral part of treatment.