Armillaria mellea fermentation liquor ameliorates p-chlorophenylalanine-induced insomnia associated with the modulation of serotonergic system and gut microbiota in rats.

In China, Armillaria mellea (Vahl) P. Kumm. has been used as a folk medicine to treat insomnia for several hundred years. However, the underlying mechanisms involved are currently unknown. In this study, the anti-insomnia efficacy of A. mellea fermentation liquor (AFL) was evaluated in p-chlorophenylalanine-induced insomnia rats by measuring the serotonergic systems and gut microbiota. Our results demonstrate that all doses of AFL significantly reduced locomotor activity and alleviated decreasing weights in insomnia rats. Further, AFL exhibited better sedative effects by reducing sleep latency and increasing sleep duration in pentobarbital-treated rats. AFL treatment also elevated serum glutathione peroxidase and superoxide dismutase levels, while reducing serum interleukin-6, tumor necrosis factor-α, and interleukin-1ß levels. Furthermore, AFL alleviated insomnia by enhancing 5-hydroxytryptamine content and the expression 5-HT1A and 5-HT2A receptor in the hippocampus. Meanwhile, AFL treatment normalized the composition of gut microbiota in insomnia-model rats, while increasing relative abundance of Lachnospiraceae, Ruminococcaceae, and Saccharimonadaceae restores the gut microbial ecosystem altered in insomnia rats. The experiments show that A. mellea alleviated insomnia by modulating serotonergic system and gut microbiota. PRACTICAL APPLICATIONS: Insomnia has become a serious health issue of global concern. As a well-known traditional Chinese medicine, Armillaria mellea has been clinically employed in the treatment of insomnia for centuries in Asia with significant efficacy. In the present study, we firstly reported A. mellea fermentation liquor potentially relieved insomnia rats by alteration of gut microbiota and serotonergic systems and could guide future clinical studies. As a popular edible and medicinal mushroom, A. mellea also can be potentially used in the development and production of novel food products in the future.

Prevalence and risk factors of belching disorders: A cross-sectional study among freshman college students.

OBJECTIVES: Belching disorders seriously affect quality of life; however, their prevalences and risk factors remain unknown. The aim of our study was to determine the prevalence and risk factors, particularly lifestyle factors, of belching disorders among freshman college students in central China. METHODS: A cross-sectional study was conducted in September 2019 in Huazhong University of Science and Technology (Wuhan, Hubei Province, China). The subjects were asked to complete a self-administered questionnaire for data collection, including sociodemographic information, lifestyle factors, and gastrointestinal symptoms. Belching disorder was diagnosed based on the Rome IV criteria. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for belching disorders. RESULTS: A total of 3335 subjects were enrolled, and 78.26% were men. Among them, 1.95% (65/3335) reported belching disorders. Significant differences in the Pittsburgh Sleep Quality Index (PSQI), Student-Life Stress Inventory (SLSI) scores, and consumption of whole grains, black tea, coffee were found between the belching and non-belching groups. Multivariate logistic regression analysis showed that coffee consumption at least once weekly and a high total SLSI score (over mean + standard deviation) were independent risk factors for belching disorders, while intake of whole grains at least once weekly was a protective factor. CONCLUSIONS: Excessive belching is a common disorder among freshman college students in central China. Lifestyle factors, including consumption of whole grains and coffee, and stress, were associated with belching disorders. Therefore, dietary intervention may be a potential management for belching disorders.

Iron deficiency in children at the time of initial neuroblastoma diagnosis.

IMPORTANCE: There is a high incidence of iron deficiency in children worldwide. Notably, however, while iron deficiency is the most common cause of anemia, little is known about the prevalence and different types of iron deficiency in neuroblastoma patients. OBJECTIVE: The aim of the present study was to investigate the prevalence of iron deficiency in patients newly diagnosed with neuroblastoma. METHODS: A total of 195 newly diagnosed neuroblastoma patients from November 2015 to January 2018 were analyzed retrospectively. The survival analysis was estimated by the Kaplan-Meier method. RESULTS: Of the 195 neuroblastoma patients included in the study, 121 (62.1%) had iron deficiency, 55 (28.2%) had absolute iron deficiency, and 66 (33.9%) had functional iron deficiency. Being aged ≥ 18 months, tumor originating in the abdomen, International Neuroblastoma Risk Group Staging System M, high-risk neuroblastoma, lactate dehydrogenase ≥ 1500 U/L, neuron-specific enolase ≥ 100 U/L, unfavorable histologic category, MYCN amplification, chromosome 1p loss, and bone marrow metastasis were associated with significantly higher rates of functional iron deficiency (P < 0.05). INTERPRETATION: Functional iron deficiency at the time of initial neuroblastoma diagnosis predicted lower event-free survival. Long-term effects of iron supplementation in neuroblastoma patients with different types of iron deficiency need to be further studied.

Astragalus polysaccharide restores autophagic flux and improves cardiomyocyte function in doxorubicin-induced cardiotoxicity.

Doxorubicin (adriamycin), an anthracycline antibiotic, is commonly used to treat many types of solid and hematological malignancies. Unfortunately, clinical usage of doxorubicin is limited due to the associated acute and chronic cardiotoxicity. Previous studies demonstrated that Astragalus polysaccharide (APS), the extracts of Astragalus membranaceus, had strong anti-tumor activities and anti-inflammatory effects. However, whether APS could mitigate chemotherapy-induced cardiotoxicity is unclear thus far. We used a doxorubicin-induced neonatal rat cardiomyocyte injury model and a mouse heart failure model to explore the function of APS. GFP-LC3 adenovirus-mediated autophagic vesicle assays, GFP and RFP tandemly tagged LC3 (tfLC3) assays and Western blot analyses were performed to analyze the cell function and cell signaling changes following APS treatment in cardiomyocytes. First, doxorubicin treatment led to C57BL/6J mouse heart failure and increased cardiomyocyte apoptosis, with a disturbed cell autophagic flux. Second, APS restored autophagy in doxorubicin-treated primary neonatal rat ventricular myocytes and in the doxorubicin-induced heart failure mouse model. Third, APS attenuated doxorubicin-induced heart injury by regulating the AMPK/mTOR pathway. The mTOR inhibitor rapamycin significantly abrogated the protective effect of APS. These results suggest that doxorubicin could induce heart failure by disturbing cardiomyocyte autophagic flux, which may cause excessive cell apoptosis. APS could restore normal autophagic flux, ameliorating doxorubicin-induced cardiotoxicity by regulating the AMPK/mTOR pathway.

Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways.

Oridonin (Ori), a diterpenoid compound extracted from traditional medicinal herbs, elicits antitumor effects on many cancer types. However, whether Ori can be used in gefitinib-resistant non-small cell lung cancer (NSCLC) cells remains unclear. This study investigated the antitumor activity and underlying mechanisms of Ori. Results demonstrated that this compound dose-dependently inhibited the proliferation, invasion, and migration of the gefitinib-resistant NSCLC cells in vitro. Ori also significantly downregulated the phosphorylation of EGFR, ERK, Akt, expression levels of matrix metalloproteinase-12 (MMP-12), and the cancerous inhibitor of protein phosphatase 2A (CIP2A). In addition, Ori upregulated protein phosphatase 2A (PP2A) activity of gefitinib-resistant NSCLC cells. Ori combined with docetaxel synergistically inhibited these cells. Ori also inhibited tumor growth in murine models. Immunohistochemistry results further revealed that Ori downregulated phospho-EGFR, MMP-12, and CIP2A in vivo. These findings indicated that Ori can inhibit the proliferation, invasion, and migration of gefitinib-resistant NSCLC cells by suppressing EGFR/ERK/MMP-12 and CIP2A/PP2A/Akt signaling pathways. Thus, Ori may be a novel effective candidate to treat gefitinib-resistant NSCLC.

Mechanical pretreatment improving hemicelluloses removal from cellulosic fibers during cold caustic extraction.

Hemicelluloses removal is a prerequisite for the production of high-quality cellulose (also known as dissolving pulp), and further recovery and utilization of hemicelluloses, which can be considered as a typical Integrated Forest Biorefinery concept. In this paper, a process of combined mechanical refining and cold caustic extraction (CCE), which was applied to a softwood sulfite sample, was investigated. The results showed that the hemicelluloses removal efficiency and selectivity were higher for the combined treatment than that for the CCE alone. The combined treatment can thus decrease the alkali concentration (from 8% to 4%) to achieve a similar hemicelluloses removal. The improved results were due to the fact that the mechanical refining resulted in increases in pore volume and diameter, water retention value (WRV) and specific surface area (SSA), all of which can make positive contributions to the hemicelluloses removal in the subsequent CCE process.