Identification of sedative-hypnotic compounds shared by five medicinal Polyporales mushrooms using UPLC-Q-TOF-MS/MS-based untargeted metabolomics.

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

MIBPred: Ensemble Learning-Based Metal Ion-Binding Protein Classifier.

In biological organisms, metal ion-binding proteins participate in numerous metabolic activities and are closely associated with various diseases. To accurately predict whether a protein binds to metal ions and the type of metal ion-binding protein, this study proposed a classifier named MIBPred. The classifier incorporated advanced Word2Vec technology from the field of natural language processing to extract semantic features of the protein sequence language and combined them with position-specific score matrix (PSSM) features. Furthermore, an ensemble learning model was employed for the metal ion-binding protein classification task. In the model, we independently trained XGBoost, LightGBM, and CatBoost algorithms and integrated the output results through an SVM voting mechanism. This innovative combination has led to a significant breakthrough in the predictive performance of our model. As a result, we achieved accuracies of 95.13% and 85.19%, respectively, in predicting metal ion-binding proteins and their types. Our research not only confirms the effectiveness of Word2Vec technology in extracting semantic information from protein sequences but also highlights the outstanding performance of the MIBPred classifier in the problem of metal ion-binding protein types. This study provides a reliable tool and method for the in-depth exploration of the structure and function of metal ion-binding proteins.

A tri-herb formulation protects against ethanol-induced mouse liver injury and downregulates mitogen-activated protein kinase phosphatase 1.

BACKGROUND: A tri-herb formulation comprising Ganoderma (the dried fruiting body of Ganoderma lucidum), Puerariae Thomsonii Radix (the dried root of Pueraria thomsonii) and Hoveniae Semen (the dried mature seed of Hovenia acerba) -GPH for short- has been using for treating liver injury; however, the pharmacological basis of this application of GPH is unknown. This study aimed to investigate the liver protective effects and mechanisms of action of an ethanolic extract of GPH (GPHE) in mice. METHODS: To control the quality of GPHE, the contents of ganodermanontriol, puerarin and kaempferol in the extract were quantified by ultra-performance liquid chromatography. An ethanol (6 ml/kg, i.g.)-induced liver injury ICR mouse model was employed to investigate the hepatoprotective effects of GPHE. RNA-sequencing analysis and bioassays were performed to reveal the mechanisms of action of GPHE. RESULTS: The contents of ganodermanontriol, puerarin and kaempferol in GPHE were 0.0632%, 3.627% and 0.0149%, respectively. Daily i.g. administration of 0.25, 0.5 or 1 g/kg of GPHE for 15 consecutive days suppressed ethanol (6 ml/kg, i.g., at day 15)-induced upregulation of serum AST and ALT levels and improved histological conditions in mouse livers, indicating that GPHE protects mice from ethanol-induced liver injury. Mechanistically, GPHE downregulated the mRNA level of Dusp1 (encoding MKP1 protein, an inhibitor of the mitogen-activated protein kinases JNK, p38 and ERK), and upregulated expression and phosphorylation of JNK, p38 and ERK, which are involved in cell survival in mouse liver tissues. Also, GPHE increased PCNA (a cell proliferation marker) expression and reduced TUNEL-positive (apoptotic) cells in mouse livers. CONCLUSION: GPHE protects against ethanol-induced liver injury, and this effect of GPHE is associated with regulation of the MKP1/MAPK pathway. This study provides pharmacological justifications for the use of GPH in treating liver injury, and suggests that GPHE has potential to be developed into a modern medication for managing liver injury.

[Epidemiological study on hyperuricemia and gout in Foshan areas, Guangdong province].

OBJECTIVE: To determine the prevalence rates and risk factors of hyperuricemia (HUA) and gout among residents aged over 20 years in Foshan areas. METHODS: A randomly stratified cluster sampling was conducted, and 7403 inhabitants were investigated on their prevalence rates of HUA and gout. RESULTS: (1) The prevalence of HUA was 15.09%, and the standardized rate was 15.27%, in which the prevalence in males was 19.90% and females was 10.54%. The prevalence of gout was 1.04% and the standardized rate was 1.08%, in which the prevalence in males was 1.73% and females was 0.39%. The prevalence of gout in patients with HUA was 6.89%. (2) Average serum uric acid was (336.4 ± 81.5) µmol/L, with (347.1 ± 88.6) µmol/L in males and (289.7 ± 78.6) µmol/L in females. The serum uric acid levels in male patients with HUA was higher than those in women. (3) Age, body mass index, systolic blood pressure, diastolic blood pressure, serum uric acid, blood sugar, triglyceride (TG), total cholesterol were significantly higher in patients with HUA and gout than in the normal group (P < 0.05 - 0.01). The incidence rates of patients with hyperuricemia and gout in the following indices as:overweight and obesity, high blood pressure, high blood sugar were significantly higher than those in the normal group (P < 0.05). Patients having gout in the following indices as age, TG, serum uric acid levels were significantly higher than the HUA group (P < 0.05). (4) Data from non-conditional logistic regression analysis showed that age, overweight, hypertension, diabetes, hyperlipidemia, use of diuretics, family history, alcohol uptake, eating seafood and drinking meat broth, post-menopausal women, and other factors were similar to those factors as patients with hyperuricemia. Tea, fresh vegetables, fruits seemed to be the protective factors. CONCLUSION: Both the prevalence rates of HUA and gout had significantly increased in Foshan areas in recent years. Restricting the intake of food with rich purine, alcohol intake as well as controlling obesity and blood pressure, improving the status of lipid metabolic disorder together with programs as hypertension control etc. were important measures in the strategies on prevention and treatment on hyperuricemia and gout.

[Study on hyperuricemia with hyperlipaemia, high blood sugar and hypertension in 1320 elderly people].

OBJECTIVE: To investigate the prevalence of hyperuricemia with hyperlipaemia, high blood sugar and hypertension among elderly people. METHODS: Serum uric acid (SUA), cholesterol, triglycerides, blood sugar and blood pressure were detected in 1320 elderly people and 6107 people at young and middle age. RESULTS: The mean SUAs in elderly male and female groups were significantly higher than that in young and middle aged male groups respectively (P < 0.05). The prevalence rates of hyperuricemia in elderly male and female groups were significantly higher than in young and middle aged male groups respectively (P < 0.05). The prevalence rates of hyperlipaemia, high blood sugar and hypertension in the elderly people of hyperuricemia were significantly higher than that in the elderly people of normal serum uric acid (P < 0.05). The prevalence rates of hyperuricemia in the elderly people were complicated by hyperlipaemia, high blood sugar and hypertension which was significantly higher than that in young and middle aged people of hyperuricemia (P < 0.05). CONCLUSION: Hyperuricemia is a common disease in elderly people and more attention should be paid to the closer relations among hyperuricemia with hyperlipaemia, high blood sugar and hypertension among the elderly.