[Status analysis and thinking on experimental study on efficacy of Mori Fructus in treatment of cardiovascular diseases].

Cardiovascular diseases are the most important diseases that endanger national health, and its development process is complex and diverse. Various cardiovascular diseases caused by obesity, such as hyperlipidemia, hyperglycemia and atherosclerosis, are interrelated and interacted each other. Diet, as the main means of prevention and treatment, plays an important role in the occurrence and development of cardiovascular disease. Mori Fructus is one of the first ingredients that are listed in medicinal and edible food. With a wide range of applications in daily life, it contains polysaccharides(polysaccharide, APS), anthocyanins(anthocyanin, LCRA), flavonoids and other bioactive ingredients. With a wide range of antioxidant, anti-aging, hypoglycemic and hypolipidemic activities, these materials exert effects in alleviating diabetes, hyperglycemia, hyperlipidemia and other cardiovascular diseases. In this paper, we retrieved such databases as PubMed, Web of science, CNKI, VTTMS, Wan Fang, and collected literatures about the effect of single administration of mulberry on cardiovascular diseases in the past 15 years, with "mulberry and cardiovascular disease" as the key word, and summarized the latest progress. The results of many experimental studies have showed that different forms of mulberry can significantly alleviate obesity, diabetes, atherosclerosis, hyperlipidemia and hypertension, suggesting that the scope of action of Mori Fructus covers different pathological stages of cardiovascular diseases. This paper systematically analyzes and summarizes the application forms, efficacy and the existing problems of these experiments, and provides study thinking and development direction for the utilization and new product design of Mori Fructus-related products in the treatment of cardiovascular diseases.

A cutting-edge deep learning-and-radiomics-based ultrasound nomogram for precise prediction of axillary lymph node metastasis in breast cancer patients ≥ 75 years.

Objective: The objective of this study was to develop a deep learning-and-radiomics-based ultrasound nomogram for the evaluation of axillary lymph node (ALN) metastasis risk in breast cancer patients ≥ 75 years. Methods: The study enrolled breast cancer patients ≥ 75 years who underwent either sentinel lymph node biopsy or ALN dissection at Fudan University Shanghai Cancer Center. DenseNet-201 was employed as the base model, and it was trained using the Adam optimizer and cross-entropy loss function to extract deep learning (DL) features from ultrasound images. Additionally, radiomics features were extracted from ultrasound images utilizing the Pyradiomics tool, and a Rad-Score (RS) was calculated employing the Lasso regression algorithm. A stepwise multivariable logistic regression analysis was conducted in the training set to establish a prediction model for lymph node metastasis, which was subsequently validated in the validation set. Evaluation metrics included area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. The calibration of the model's performance and its clinical prediction accuracy were assessed using calibration curves and decision curves respectively. Furthermore, integrated discrimination improvement and net reclassification improvement were utilized to quantify enhancements in RS. Results: Histological grade, axillary ultrasound, and RS were identified as independent risk factors for predicting lymph node metastasis. The integration of the RS into the clinical prediction model significantly improved its predictive performance, with an AUC of 0.937 in the training set, surpassing both the clinical model and the RS model alone. In the validation set, the integrated model also outperformed other models with AUCs of 0.906, 0.744, and 0.890 for the integrated model, clinical model, and RS model respectively. Experimental results demonstrated that this study's integrated prediction model could enhance both accuracy and generalizability. Conclusion: The DL and radiomics-based model exhibited remarkable accuracy and reliability in predicting ALN status among breast cancer patients ≥ 75 years, thereby contributing to the enhancement of personalized treatment strategies' efficacy and improvement of patients' quality of life.

Effects of Poria cocos extract and protein powder mixture on glucolipid metabolism and rhythm changes in obese mice.

Herein, we explored the effects of Poria cocos extract, protein powder mixture, and their combined intervention on weight loss in high-fat diet (HFD)-induced obese mice. Male C57BL/6J mice were selected and fed a HFD for 8 weeks; obese mice that were successfully modeled were divided into modeling and five intervention groups, and given the corresponding treatment for 10 weeks. Body weight, fat, and muscle tissue, blood glucose, lipids, inflammatory factors, and other glucose and lipid metabolism-related indicators were measured to evaluate the effect of P. cocos and protein powder intervention on weight loss in obese mice. The body weight of the intervention group was reduced compared with the HFD group. Fat content of mice in F3PM group decreased significantly (p < .05). Levels of blood glucose, lipids, adiponectin, leptin, and inflammatory factors, including interleukin-1 ß and tumor necrosis factor- α showed improvement. Lipoprotein lipase (lower about 2.97 pg/ml, vs. HFD mice 10.65 mmoL/ml) and sterol regulatory element-binding transcription factor (lower about 1413.63 pg/ml, vs. HFD mice 3915.33 pg/ml) levels in liver tissue were decreased. The respiratory exchange rate (RER) of mice in the HFD and subject intervention groups had no circadian rhythm and was maintained at approximately 0.80. The protein powder mixture (PM) group had the lowest RER (p < .05), the P. cocos extract (FL) and F1PM groups had similar RER to the HFD group (p < .05), and the F2PM group had a higher RER than the HFD group (p < .05). And food intake and energy metabolism returned to circadian rhythm, with an increase in the dose of P. cocos extract, the feeding rhythms of F1PM, F2PM, and F3PM were closer to that of the normal diet (ND) group. Feeding intervention with P. cocos and protein powder improved fat distribution, glucolipid metabolism, and energy metabolism, with the combination of F3PM showing more diverse benefits.

The effects of Ascophyllum nodosum, Camellia sinensis-leaf extract, and their joint interventions on glycolipid and energy metabolism in obese mice.

Objectives: Obesity is often associated with glucolipid and/or energy metabolism disorders. Ascophyllum nodosum extract (seaweed extract, SE) and Camellia sinensis-leaf extract (tea extract, TE) have been reported to promote positive metabolic effects through different mechanisms. We investigated the effects of SE and TE on metabolic homeostasis in diet-induced obese mice and discussed their functional characteristics. Methods: Male C57BL/6J mice fed with high-fat diets for 8 weeks were established as obese models and subsequently divided into different intervention groups, followed by SE, TE, and their joint interventions for 10 weeks. Body weight and food intake were monitored. Fasting glucose and oral glucose tolerance tests were interspersed during the experiment. After the intervention, the effects on obesity control were assessed based on body composition, liver pathology section, blood lipids and glucose, respiratory exchange ratio (RER), energy expenditure (EE1, EE2, and EE3), inflammatory factors, lipid anabolism enzymes, and gut flora of the obese mice. Results: After continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower ~4.93 g, vs. HFD 38.02 g), peri-testicular fat masses (lower ~0.61 g, vs. HFD 1.92 g), and perirenal fat masses (lower ~0.21 g, vs. HFD mice 0.70 g). All interventions prevented diet-induced increases in plasma levels of glucose, adiponectin, leptin, and the inflammatory factors IL-1ß and TNF-α. The RER was modified by the interventions, while the rhythm of the RER was not. Blood lipids (total cholesterol, triglycerides, and LDL) decreased and were associated with lower lipid anabolism enzymes. In addition, the SE and TE interventions altered the structure and abundance of specific flora. Different interventions inhibited the growth of different genera positively associated with obesity (Escherichia-Shigella, Helicobacter, etc.) and promoted the growth of Akkermansia and Bacteroides, thus affecting the chronic inflammatory state. Conclusion: SE and TE both have synergistic effects on weight control and glucolipid metabolism regulation by improving insulin sensitivity and reducing lipid synthesis-related enzyme expression, whereas the combination of SE and TE (3:1) has a better effect on regulating energy metabolism and inhibiting chronic inflammation.

Eight Weeks of Bifidobacterium lactis BL-99 Supplementation Improves Lipid Metabolism and Sports Performance through Short-Chain Fatty Acids in Cross-Country Skiers: A Preliminary Study.

(1) Background: Probiotics in the form of nutritional supplements are safe and potentially useful for strategic application among endurance athletes. Bifidobacterium animalis lactis BL-99 (BL-99) was isolated from the intestines of healthy Chinese infants. We combined plasma-targeted metabolomics and fecal metagenomics to explore the effect of 8 weeks of BL-99 supplementation on cross-country skiers' metabolism and sports performance. (2) Methods: Sixteen national top-level male cross-country skiers were recruited and randomly divided into a placebo group (C) and a BL-99 group (E). The participants took the supplements four times/day (with each of three meals and at 21:00) consistently for 8 weeks. The experiment was conducted in a single-blind randomized fashion. The subject's dietary intake and total daily energy consumption were recorded. Blood and stool samples were collected before and after the 8-week intervention, and body composition, muscle strength, blood biochemical parameters, plasma-targeted metabolomic data, and fecal metagenomic data were then analyzed. (3) Results: The following changes occurred after 8 weeks of BL-99 supplementation: (a) There was no significant difference in the average total daily energy consumption and body composition between the C and E groups. (b) The VO2max and 60°/s and 180°/s knee joint extensor strength significantly increased in both the C and E groups. By the eighth week, the VO2max and 60 s knee-joint extensor strength were significantly higher in the E group than in the C group. (c) The triglyceride levels significantly decreased in both the C and E groups. In addition, the LDL-C levels significantly decreased in the E group. (d) The abundance of Bifidobacterium animalis increased two-fold in the C group and forty-fold in the E group. (e) Plasma-targeted metabolomic analysis showed that, after eight weeks of BL-99 supplementation, the increases in DHA, adrenic acid, linoleic acid, and acetic acid and decreases in glycocholic acid and glycodeoxycholic acid in the E group were significantly higher than those in the C group. (f) Spearman correlation analysis showed that there was a significant positive correlation between Bifidobacterium animalis' abundance and SCFAs, PUFAs, and bile acids. (g) There was a significant correlation between the most significantly regulated metabolites and indicators related to sports performance and lipid metabolism. (4) Conclusions: Eight weeks of BL-99 supplementation combined with training may help to improve lipid metabolism and sports performance by increasing the abundance of Bifidobacterium, which can promote the generation of short-chain fatty acids and unsaturated fatty acids, and inhibit the synthesis of bile acids.

Effects of Coix seed extract, Lactobacillus paracasei K56, and their combination on the glycolipid metabolism in obese mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism through different modes of action. We tested the effects of CSE, Lactobacillus paracasei K56, and their combination to determine whether they have synergistic effects on glycolipid metabolism of obese mice. We fed male C57BL/6J mice with high-fat diet for 8 weeks to establish an obesity model. The obesity mice were selected and divided into five groups: the model control group and four intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31-4.41 g, vs. HFD 42.25 g, p < 0.01), and epididymal (lower about 0.58-0.92 g, vs. HFD 2.50 g, p < 0.01) and perirenal fat content (lower about 0.24-0.42 g, vs. HFD 0.88 g, p < 0.05); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. K56 + CSE-combined intervention groups were more effective in lowering blood glucose, IL-1ß, and TNF-α levels than the CSE and K56 alone interventions. The content of fatty acid synthase and SREBP-1c protein in liver tissue was lower. The combination has synergistic effects on weight control, fat reduction, and blood glucose regulation by improving the chronic inflammatory state and reducing the content of lipid synthesis-related enzymes of obese mice, which can hinder chronic disease progression. PRACTICAL APPLICATION: Coix seed extract can be used in obese people to regulate abnormal glucose and lipid metabolism and delay the development of chronic diseases.

Nutrient combinations exhibit universal antianxiety, antioxidant, neuro-protecting, and memory-improving activities.

Anxiety disorders are the most common mental disorders and, without proper treatment, may lead to severe conditions: e.g., somatic disorders or permanent damage to central nervous system. Although there are drugs in clinical trials, this study focuses on exploring the efficacy of nutrients in treating these diseases. We built different zebrafish models and screened several nutrient combinations for their antianxiety, antioxidant, neuro-protecting, and memory-improving activities. Our results showed that the combinations of nutrients (e.g., Walnut Peptides + Theanine at 14.2 + 33.3 µg/ml) have similar or better activities than the positive control drugs. In addition, we discovered that the effects of the nutrients in the above four aspects were universal and highly related. This study is noteworthy as it suggested that nutrients could be healthier and greener drug alternatives and provide similar or better universal treatments for anxiety and related conditions.

Effects of Coix Seed Extract, Bifidobacterium BPL1, and Their Combination on the Glycolipid Metabolism in Obese Mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism via different modes of action. We tested the effects of CSE, Bifidobacterium BPL1, and their combination to determine their effects on glycolipid metabolism in obese mice. Male C57BL/6J mice were fed a high-fat diet for 8 weeks to establish an obesity model. Obese mice were selected and divided into four groups: the model control group and three intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31 g, vs. HFD mice 42.23 g) and epididymal (lower about 0.37 g, vs. HFD mice 2.5 g) and perirenal fat content (lower about 0.47 g, vs. HFD mice 0.884 g); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. CSE, BPL1 and their combination can effectively control the weight gain in obese mice, reduce fat content, and regulate blood lipids and abnormal blood sugar. These results may be related to reduce the chronic inflammatory states, improve energy metabolism, exercise, relieve insulin sensitivity, and reduce lipid synthesis via the intervention of CSE, BPL1 and their combination. Compared with the single use of CSE alone, the combination of CSE + BPL1 can better exert the regulation function of intestinal flora, and change in the abundance of bacteria that could improve the level of inflammatory factors, such as increasing Bifidobacterium, reducing Lactococcus. Compared with the use of BPL1 alone, the combination of CSE and BPL1 can better regulate pancreatic islet and improve blood sugar. CSE may act directly on body tissues to exert anti-inflammatory effects. BPL1 and CSE + BPL1 may improve the structure and function of the intestinal flora, and reduce tissue inflammation.

Slowly Digestible Carbohydrate Diet Ameliorates Hyperglycemia and Hyperlipidemia in High-Fat Diet/Streptozocin-Induced Diabetic Mice.

Objective: Given that the prevalence rate of type 2 diabetes mellitus (T2DM) continues to increase, it is important to find an effective method to prevent or treat this disease. Previous studies have shown that dietary intervention with a slowly digestible carbohydrate (SDC) diet can improve T2DM with almost no side effects. However, the underlying mechanisms of SDC protect against T2DM remains to be elucidated. Methods: The T2DM mice model was established with a high-fat diet and streptozocin injection. Then, SDC was administered for 6 weeks. Bodyweight, food intake, organ indices, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), homeostasis model assessment for insulin resistance (HOMA-IR), and other biochemical parameters were measured. Histopathological and lipid accumulation analyses were performed, and the glucose metabolism-related gene expressions in the liver and skeletal muscle were determined. Lastly, colonic microbiota was also analyzed. Results: SDC intervention alleviated the weight loss in the pancreas, lowered blood glucose and glycosylated hemoglobin levels, and improved glucose tolerance and HOMA-IR. SDC intervention improved serum lipid profile, adipocytokines levels, and lowered the lipid accumulation in the liver, subcutaneous adipose tissue, and epididymal visceral adipose tissue. In addition, SDC intervention increased the expression levels of IRS-2 and GLUT-2 in liver tissues and elevated GLUT-4 expression levels in skeletal muscle tissues. Notably, SDC intervention decreased the Bacteroidetes/Firmicutes ratio, increased Desulfovibrio and Lachnospiraceae genus levels, and inhibited the relative abundance of potentially pathogenic bacteria. Conclusions: SDC intervention can improve hyperglycemia and hyperlipidemia status in diabetic mice, suggesting that this intervention might be beneficial for T2DM.

[Quality analysis of Ziziphi Spinosae Semen extracts based on high performance liquid chromatography quantitative fingerprint and ultra-high performance liquid chromatography-tandem mass spectrometry quantification].

Ziziphi Spinosae Semen is the dried seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou, and its extract has broad application prospects in the development of sleep-aid functional foods. However, the quality parameters of Ziziphi Spinosae Semen extracts currently available in the market are not uniform and there is a lack of unified standards. Therefore, it is important to establish an accurate and comprehensive method for quality evaluation. In view of the problems that the UV responses of flavonoids and saponins in the Ziziphi Spinosae Semen extracts vary dramatically and the saponin content in Ziziphi Spinosae Semen water extract is very low, high performance liquid chromatography (HPLC) was used to establish the fingerprint and quantify spinosin. The separation was carried out on a Waters XSelect HSS C18 column (250 mm×4.6 mm, 5 µm), and the mobile phase was acetonitrile-0.1% (v/v) phosphoric acid aqueous solution for gradient elution. The eight common peaks in the fingerprint of the Ziziphi Spinosae Semen extracts, identified by HPLC-quadrupole time-of-flight mass spectrometry, were attributed to flavonoids by reference substance identification, literature comparison, and high-resolution mass spectrometry data analysis. Semi-quantitative analysis of seven flavonoids and quantitative analysis of spinosin were conducted using the established HPLC quantitative fingerprint. The contents of jujuboside A and jujuboside B were determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm) by gradient elution using a mobile phase of acetonitrile-0.1%(v/v) formic acid aqueous solution. The target compounds were analyzed in multiple reaction monitoring mode with positive electrospray ionization. The semi-quantitative and quantitative data of the above-mentioned 10 components are displayed in the form of radar. Using the above methods, three batches of Ziziphi Spinosae Semen water extracts prepared in the laboratory and 15 batches of extract samples obtained from 15 suppliers were analyzed and compared. The results showed that although the raw materials of three batches of Ziziphi Spinosae Semen water extracts prepared in the laboratory were from different enterprises, the overall difference was not significant. However, the component contents of the samples provided by different manufacturers were greatly different, suggesting that there are some problems associated with the different manufacturers, such as dilution of excipients, adulteration of Ziziphi Mauritianae Semen, alcohol extraction, purification, and enrichment. For example, the representative composition contents in the Ziziphi Spinosae Semen extracts obtained from manufacturers B, C, E, F, G, H, I, and O were low, which were approximately 1/10 of corresponding contents in the normal water extracts prepared in the laboratory. It is speculated that to reduce the unit price of the product, the manufacturer used fewer raw materials or a large number of auxiliary materials to dilute the Ziziphi Spinosae Semen extracts. The contents of some flavonoids in the Ziziphi Spinosae Semen extract from manufacturer N were slightly higher than that in the self-preparation Ziziphi Spinosae Semen water extract, but it did not contain jujuboside A; thus, it was speculated that the Ziziphi Mauritianae Semen might be used for extraction. The contents of 10 components in the Ziziphi Spinosae Semen extract obtained from manufacturer D were all higher than the corresponding ones in the self-preparation Ziziphi Spinosae Semen water extract. Combined with the quality label of total saponin content > 20% and poor water solubility, it was speculated that the product might be prepared by alcohol extraction or purified and enriched by using resin. These results provided the basis for the enterprise to establish internal control quality standards for Ziziphi Spinosae Semen extracts and to select qualified suppliers.

The combined use of gamma-aminobutyric acid and walnut peptide enhances sleep in mice.

BACKGROUND: γ-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid in the nervous system and has a wide range of physiological functions in the body. Walnut peptide (WP) contains high levels of arginine, aspartic acid, and glutamate, and has been shown to improve cognitive deficits and memory impairment in mice, while restoring antioxidant enzyme levels and reducing brain inflammatory mediators. METHODS: This study investigated the effects of GABA and WP, either alone or in combination, on sleep disturbances in mice. The pentobarbital-prolonged sleep test, pentobarbital-threshold sleep test, and barbital-induced sleep test were conducted to assess the effects of GABA and WP on sleep quality by gavage for 30 days as follows: GABA (102.25 mg/kg), WP (102.25 mg/kg), GABA (33.95, 102.25, 306.75 mg/kg)/WP (102.25 mg/kg) mixture. Furthermore, neurotransmitter tests were performed using mice brain tissue to investigate the possible mechanisms of GABA and WP on sleep status. RESULTS: The results showed that the combined use of GABA and WP significantly increased sleep duration compared with single administration of either WP or GABA. Increasing doses of GABA in mice treated with combined GABA and WP elevated the sleep rate to 50.00%, 64.28%, and 64.28%, respectively, compared to mice treated with GABA alone (35.71%) or mice treated with WP alone (28.57%). In mice that received a combination of GABA and WP orally, the latency time was significantly decreased after 30 days compared to control mice (P<0.05). Additionally, in mice treated with GABA, WP, or the combination of GABA and WP, the concentrations of GABA and acetylcholine (Ach) in the brain were significantly elevated and the concentration of serotonin (5-HT) was decreased compared to untreated mice. CONCLUSIONS: These results demonstrated that the combined administration of GABA and WP could prolong the sleep duration, increase sleep rate, and shorten the sleep latency more effectively than the administration of either GABA or WP alone. The mechanisms of action may be related to the regulation of neurotransmitters in the brain tissue by the combination of GABA and WP.