Enhancement of ergothioneine production by discovering and regulating its metabolic pathway in Cordyceps militaris.

BACKGROUND: Cordyceps militaris is a traditional medicinal fungus contains a variety of functional ingredients and has been developed as an important mushroom food recently. Ergothioneine, one of the antioxidative compounds in C. militaris, is benefits on aging-related diseases and therefore became a novel functional food nutritive fortifier. Currently, the main diet source of ergothioneine is mushroom food. However, the mushroom farming faces the problems such as rather low ingredient yield and spontaneous degeneration associated fruiting body that restricts large scale production of ergothioneine. RESULTS: In this study, we excavated the ergothioneine synthetases in mushroom and modified the genes in C. militaris to construct a new ergothioneine synthesis pathway. By further introducing this pathway into C. militaris genome, we succeeded to increase the ingredients' production of engineering strain, the highest amount of ergothioneine and cordycepin were up to 2.5 g/kg dry weight and 2 g/L, respectively. Additionally, the expression of ergothioneine synthetase genes in the shape-mutated degenerative C. militaris could recover the ability of degenerative strain to produce high amount of ingredients, suggesting the metabolic regulation of ergothioneine might release the symptom of mushroom degeneration. CONCLUSION: This study reveals a new pathway to fulfill the market needs of functional mushroom food and food fortifier ergothioneine. It implied the mycelium of C. militaris could be engineered as a novel medicinal mushroom food which could produce higher amount of valuable ingredients.

Nonalcoholic fatty liver disease impacts the control of the international normalized ratio in patients with atrial fibrillation.

BACKGROUND: It is unclear whether the therapeutic effect of warfarin in patients with atrial fibrillation (AF) and normal liver function differs between those with and without nonalcoholic fatty liver disease (NAFLD). With this in mind, we aimed to evaluate the impact of NAFLD on the international normalized ratio (INR) control in warfarin-treated AF patients with normal liver function. METHODS: We enrolled 600 AF patients aged 28-94 (median 68) with normal liver function who were receiving daily warfarin therapy, 172 with NAFLD and 428 without. The INR and INR/warfarin dosage rate were measured. Four nested multivariable linear regression models adjusted for potential confounders were used to assess whether there were differences in INR and INR/warfarin dose rate between patients with and without NAFLD. RESULTS: The INR, the percentage of patients with INR within the target range of 2.0-3.0, and the INR/warfarin dose rate were lower in patients with NAFLD than those without. In the maximally adjusted multivariable linear regression models, the INR in NAFLD patients (0.22±0.07, P=0.003) was lower than in non-NAFLD patients, and the INR/warfarin dose rate was slightly lower (0.09±0.06, P=0.10) in NAFLD than in non-NAFLD patients. CONCLUSIONS: Our findings suggest that among AF patients, the therapeutic effect of warfarin is impaired in patients who have NAFLD. Therefore, a slightly higher or personally optimized dosage of warfarin might be necessary among AF patients with NAFLD in order to achieve the INR target range.

Prolonged P-wave duration is associated with atrial fibrillation recurrence after radiofrequency catheter ablation: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: A change in the P-wave duration (PWD) was made in patients with atrial fibrillation recurrence (AFR) after radiofrequency catheter ablation (RFCA). The correlation between the PWD and AFR and the potential utilization of a prolonged PWD in the prediction of AFR after RFCA remains unclear. METHODS: Studies of PWD in patients with or without AFR after RFCA, and studies concerned with the predictive effect of prolonged PWD on AFR after RFCA, were included. Outcome measures are reported as absolute risk differences with 95% confidence intervals. A receiver operating characteristic (ROC) curve was used to evaluate the potential cutoff value of PWD for AFR. Summary receiver operating characteristic curve (SROC) analysis was performed to show the overall predictive value of PWD for AFR. RESULTS: Nine studies were included. The overall effect test based on 8 studies that contained a total cohort of 1010 patients showed a highly significant association between prolonged PWD and AFR after RFCA (Z=14.20, P<0.000). A summary that included 4 studies with a combined total of 593 patients indicated a higher risk of AFR in patients with prolonged PWD (Z=5.86, P<0.000). ROC curve analysis indicated 149.5ms as the potential cutoff value of PWD for AFR after RFCA. SROC analysis suggested an acceptable predictive efficiency of PWD for AFR (AUC=0.66). CONCLUSIONS: The risk of AFR after RFCA is strongly related to a prolonged PWD. PWD is one potential low-cost and feasible predictor of AFR after RFCA.