Targeting deoxynivalenol for degradation by a chimeric manganese peroxidase/glutathione system.

The manganese peroxidase (MnP) can degrade multiple mycotoxins including deoxynivalenol (DON) efficiently; however, the lignin components abundant in foods and feeds were discovered to interfere with DON catalysis. Herein, using MnP from Ceriporiopsis subvermispora (CsMnP) as a model, it was demonstrated that desired catalysis of DON, but not futile reactions with lignin, in the reaction systems containing feeds could be achieved by engineering MnP and supplementing with a boosting reactant. Specifically, two successive strategies (including the fusion of CsMnP to a DON-recognizing ScFv and identification of glutathione as a specific targeting enhancer) were combined to overcome the lignin competition, which together resulted into elevation of the degradation rate from 2.5% to as high as 82.7% in the feeds. The method to construct a targeting MnP and fortify it with an additional enhancer could be similarly applied to catalyze the many other mycotoxins with yet unknown responsive biocatalysts.

Production of capsaicinoid nonivamide from plant oil and vanillylamine via whole-cell biotransformation.

Capsaicinoids are mostly derived from chili peppers and have widespread applications in food, feed, and pharmacology. Compared with plant extraction, the use of microbial cell factories for capsaicinoids production is considered as a more efficient approach. Here, the biotransformation of renewable plant oil and vanillylamine into capsaicinoid nonivamide was investigated. Nonivamide biosynthesis using nonanoic acid and vanillylamine as substrates was achieved in Escherichia coli by heterologous expression of genes encoding amide-forming N-acyltransferase and CoA-ligase. Through increasing nonanoic acid tolerance of chassis cell, screening key enzymes involved in nonivamide biosynthesis and optimizing biotransformation conditions, the nonivamide titer reached 0.5 g/L. By further integrating a route for conversion of oleic acid to nonanoic acid, nonivamide biosynthesis was finally achieved using olive oil and vanillylamine as substrates, yielding a titer of approximately 10.7 mg/L. Results from this study provide valuable information for constructing highly efficient cell factories for the production of capsaicinoid compounds.

Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity.

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia-Shigella, which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.

Identification and Characterization of the Determinants of Copper Resistance in the Acidophilic Fungus Acidomyces richmondensis MEY-1 Using the CRISPR/Cas9 System.

Copper (Cu) homeostasis has not been well documented in filamentous fungi, especially extremophiles. One of the main obstacles impeding their characterization is the lack of a powerful genome-editing tool. In this study, we applied a CRISPR/Cas9 system for efficient targeted gene disruption in the acidophilic fungus Acidomyces richmondensis MEY-1, formerly known as Bispora sp. strain MEY-1. Using this system, we investigated the basis of Cu tolerance in strain MEY-1. This strain has extremely high Cu tolerance among filamentous fungi, and the transcription factor ArAceA (A. richmondensis AceA) has been shown to be involved in this process. The ArAceA deletion mutant (ΔArAceA) exhibits specific growth defects at Cu concentrations of ≥10 mM and is transcriptionally more sensitive to Cu than the wild-type strain. In addition, the putative metallothionein ArCrdA was involved in Cu tolerance only under high Cu concentrations. MEY-1 has no Aspergillus nidulans CrpA homologs, which are targets of AceA-like transcription factors and play a role in Cu tolerance. Instead, we identified the Cu-transporting P-type ATPase ArYgA, homologous to A. nidulans YgA, which was involved in pigmentation rather than Cu tolerance. When the ΔArYgA mutant was grown on medium supplemented with Cu ions, the black color was completely restored. The lack of CrpA homologs in A. richmondensis MEY-1 and its high tolerance to Cu suggest that a novel Cu detoxification mechanism differing from the AceA-CrpA axis exists. IMPORTANCE Filamentous fungi are widely distributed worldwide and play an important ecological role as decomposers. However, the mechanisms of their adaptability to various environments are not fully understood. Various extremely acidophilic filamentous fungi have been isolated from acidic mine drainage (AMD) with extremely low pH and high heavy metal and sulfate concentrations, including A. richmondensis. The lack of genetic engineering tools, particularly genome-editing tools, hinders the study of these acidophilic and heavy metal-resistant fungi at the molecular level. Here, we first applied a CRISPR/Cas9-mediated gene-editing system to A. richmondensis MEY-1. Using this system, we identified and characterized the determinants of Cu resistance in A. richmondensis MEY-1. The conserved roles of the Cu-binding transcription factor ArAceA in Cu tolerance and the Cu-transporting P-type ATPase ArYgA in the Cu-dependent production of pigment were confirmed. Our findings provide insights into the molecular basis of Cu tolerance in the acidophilic fungus A. richmondensis MEY-1. Furthermore, the CRISPR/Cas9 system used here would be a powerful tool for studies of the mechanisms of adaptability of acidophilic fungi to extreme environments.

Drosophila melanogaster diabetes models and its usage in the research of anti-diabetes management with traditional Chinese medicines.

The prevalence of diabetes mellitus (DM) is increasing rapidly worldwide, but the underlying molecular mechanisms of disease development have not been elucidated, and the current popular anti-diabetic approaches still have non-negligible limitations. In the last decades, several different DM models were established on the classic model animal, the fruit fly (Drosophila melanogaster), which provided a convenient way to study the mechanisms underlying diabetes and to discover and evaluate new anti-diabetic compounds. In this article, we introduce the Drosophila Diabetes model from three aspects, including signal pathways, established methods, and pharmacodynamic evaluations. As a highlight, the progress in the treatments and experimental studies of diabetes with Traditional Chinese Medicine (TCM) based on the Drosophila Diabetes model is reviewed. We believe that the values of TCMs are underrated in DM management, and the Drosophila Diabetes models can provide a much more efficient tool to explore its values of it.

Metabolic engineering of Pichia pastoris for myo-inositol production by dynamic regulation of central metabolism.

BACKGROUND: The methylotrophic budding yeast Pichia pastoris GS115 is a powerful expression system and hundreds of heterologous proteins have been successfully expressed in this strain. Recently, P. pastoris has also been exploited as an attractive cell factory for the production of high-value biochemicals due to Generally Recognized as Safe (GRAS) status and high growth rate of this yeast strain. However, appropriate regulation of metabolic flux distribution between cell growth and product biosynthesis is still a cumbersome task for achieving efficient biochemical production. RESULTS: In this study, P. pastoris was exploited for high inositol production using an effective dynamic regulation strategy. Through enhancing native inositol biosynthesis pathway, knocking out inositol transporters, and slowing down carbon flux of glycolysis, an inositol-producing mutant was successfully developed and low inositol production of 0.71 g/L was obtained. The inositol production was further improved by 12.7% through introduction of heterologous inositol-3-phosphate synthase (IPS) and inositol monophosphatase (IMP) which catalyzed the rate-limiting steps for inositol biosynthesis. To control metabolic flux distribution between cell growth and inositol production, the promoters of glucose-6-phosphate dehydrogenase (ZWF), glucose-6-phosphate isomerase (PGI) and 6-phosphofructokinase (PFK1) genes were replaced with a glycerol inducible promoter. Consequently, the mutant strain could be switched from growth mode to production mode by supplementing glycerol and glucose sequentially, leading to an increase of about 4.9-fold in inositol formation. Ultimately, the dissolved oxygen condition in high-cell-density fermentation was optimized, resulting in a high production of 30.71 g/L inositol (~ 40-fold higher than the baseline strain). CONCLUSIONS: The GRAS P. pastoris was engineered as an efficient inositol producer for the first time. Dynamic regulation of cell growth and inositol production was achieved via substrate-dependent modulation of glycolysis and pentose phosphate pathways and the highest inositol titer reported to date by a yeast cell factory was obtained. Results from this study provide valuable guidance for engineering of P. pastoris for the production of other high-value bioproducts.

Silybin B exerts protective effect on cisplatin-induced neurotoxicity by alleviating DNA damage and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Silybum marianum is a traditional Chinese medicine that has been used for treating liver disease. Silybin consisting of silybin A and silybin B, is a member of Silybum marianum, and exerts a therapeutic effect on many diseases. However, the protective effect of silybin on cisplatin-induced neurotoxicity and the stereoisomer contributing to the effect remain unknown. AIM OF THE STUDY: The present study aimed to study the effect of silybin on cisplatin-induced neuronal injury, compare the difference of protective effect between silybin A and silybin B, and the potential mechanism. MATERIALS AND METHODS: High performance liquid chromatography (HPLC) was used to separate silybin A and silybin B. X-ray crystallographic analysis in combination with experimental and calculated ECD were performed to identify the structure of silybin A and silybin B. The toxicity of the silybin or cisplatin against murine hippocampal neuronal HT22 cells was determined through MTT assay. The cell cycle and cell apoptosis were measured by PI staining and Annexin V-FITC/PI staining, respectively, and then subjected to flow cytometry. Western blot analysis was conducted to quantify the expression of proteins related to apoptosis and DNA damage. Immunofluorescence was used to evaluate the expression of DNA damage marker. In vivo experiment, the behavioral analysis was determined through pole test, swimming test and Morris water maze test. The index of superoxide dismutase (SOD), reduced glutathione (GSH), total antioxidant capacity (T-AOC) and lipid peroxidation (LPO) were examined to evaluate the antioxidant capacity in mice brain. Nissl staining and Tunel assay were used to detect the neuronal viability and apoptosis in hippocampus. RESULTS: We successfully separated and identified silybin A and silybin B. We found both silybin A and silybin B alleviated cisplatin-induced apoptosis and cell cycle arrest in HT22 cells, and silybin B was more effective. We chose silybin B for further mechanism investigation, and found silybin B alleviated DNA damage by enhancing phosphorylation of ATR and decreasing expression of γ-H2AX. In the in vivo experiment, we observed that silybin B markedly improved the behavioral abnormalities in cisplatin-treated mice, reduced LPO level while increased SOD, GSH and T-AOC in mice brain tissue. Nissl staining and Tunel assay showed that silybin B alleviated cisplatin-induced hippocampal damage. CONCLUSIONS: These results suggest that silybin B might serve as a promising drug candidate in mitigating cisplatin-induced neural injury in the brain and thereby improving the chemotherapeutic outcomes.

Chemical profiling of root bark extract from Oplopanax elatus and its in vitro biotransformation by human intestinal microbiota.

Oplopanax elatus (Nakai) Nakai, in the Araliaceae family, has been used in traditional Chinese medicine (TCM) to treat diseases as an adaptogen for thousands of years. This study established an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method to identify chemical components and biotransformation metabolites of root bark extract from O. elatus. A total of 18 compounds were characterized in O. elatus extract, and 62 metabolites by human intestinal microbiota were detected. Two polyynes, falcarindiol and oplopandiol were recognized as the main components of O. elatus, whose metabolites are further illustrated. Several metabolic pathways were proposed to generate the detected metabolites, including methylation, hydrogenation, demethylation, dehydroxylation, and hydroxylation. These findings indicated that intestinal microbiota might play an essential role in mediating the bioactivity of O. elatus.

Clinical Effects of Integrated Traditional Chinese and Western Medicine in Treating Severe Preeclampsia and Its Influence on Maternal and Infant Outcomes after Cesarean Section under Combined Lumbar and Epidural Anesthesia.

OBJECTIVE: This study is aimed to observe the clinical effects of integrated traditional Chinese and Western medicine in treating severe preeclampsia (SPE) and its effects on maternal and infant outcomes after cesarean section under combined lumbar and epidural anesthesia. METHOD: One hundred and sixty-six pregnant women with SPE were randomly divided into an experimental group and control group, with 83 cases in each group. The control group was given conventional treatments such as magnesium sulfate, and the experimental group received self-made traditional Chinese medicine decoction for oral administration. RESULTS: The total clinical effective rate of treatment in the experimental group was significantly higher than that in the control group. After treatment, the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and 24 h proteinuria (24 h PRO) levels of the experimental group were significantly lower than those of the control group. After cesarean section (c-section) under combined lumbar and epidural anesthesia, there were statistically significant differences in placental abruption, uterine weakness, fetal intrauterine distress, and neonatal asphyxia in the experimental group, while there were no significant differences in oligohydramnios. After treatment, the contents of inflammatory factors in both groups decreased, and the decrease was more prominent in the experimental group. After treatment, the levels of blood urea nitrogen (BUN), serum creatinine (Scr), and albumin (Alb) and ß2 microglobulin (ß2-MG) of the two groups of patients decreased, and the levels of them in the experimental group decreased. After treatment, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the two groups increased. However, the levels of malondialdehyde (MDA), lipid peroxide (LPO), and advanced oxidation protein products (AOPP) all reduced, and the increase or decrease in the experimental group was more prominent. CONCLUSION: The combination of traditional Chinese and Western medicine can reduce the blood pressure of a patient with SPE. After the combined spinal-epidural anesthesia and cesarean section, it can significantly improve the maternal and infant outcomes and renal function, reduce inflammatory factors levels and body oxidative stress, and increase the activities of antioxidant enzymes.

Effects of algal blooms on selenium species dynamics: A case study in the Changjiang Estuary, China.

The selenium cycle in the marine environment is sensitive to biological activity, but knowledge of dissolved Se species dynamics during coastal algal blooms is limited. Selenium species dynamics during diatom blooms in the Changjiang Estuary were investigated in a survey of dissolved inorganic and organic Se. Dissolved inorganic Se (Se(IV) + Se(VI)) was the predominant species in river-dominanated areas, while dissolved organic selenide (DOSe) was predominant in ocean-dominanated areas. Relationships between DOSe and chromophoric dissolved organic matter involved both humic- and protein-like components, suggesting distinct sources of DOSe in river- and ocean-dominance areas, respectively. A three-endmember-mixing model was used to describe biological processes in ocean-dominanated surface waters. In diatom-bloom areas, the co-occurrence of depletion of Se(IV) and Se(VI) (of ~90% and 30%, respectively) and a 44% increase in production of DOSe indicates that phytoplankton act as vectors for Se species transformation. A Se(IV)*P indicator was developed to quantify limiting concentrations of Se(IV) in water relative to that of phosphorus. Negative Se(IV)*P concentrations indicate that Se(IV) is limited due to biological utilization of dissolved inorganic phosphorus by diatoms, resulting in secondary uptake of Se(VI) in the Changjiang Estuary.

Protection against chemotherapy- and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals.

BACKGROUND: Although great achievements have been made in the field of cancer therapy, chemotherapy and radiotherapy remain the mainstay cancer therapeutic modalities. However, they are associated with various side effects, including cardiocytotoxicity, nephrotoxicity, myelosuppression, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, mucositis, and alopecia, which severely affect the quality of life of cancer patients. Plants harbor a great chemical diversity and flexible biological properties that are well-compatible with their use as adjuvant therapy in reducing the side effects of cancer therapy. PURPOSE: This review aimed to comprehensively summarize the molecular mechanisms by which phytochemicals ameliorate the side effects of cancer therapies and their potential clinical applications. METHODS: We obtained information from PubMed, Science Direct, Web of Science, and Google scholar, and introduced the molecular mechanisms by which chemotherapeutic drugs and irradiation induce toxic side effects. Accordingly, we summarized the underlying mechanisms of representative phytochemicals in reducing these side effects. RESULTS: Representative phytochemicals exhibit a great potential in reducing the side effects of chemotherapy and radiotherapy due to their broad range of biological activities, including antioxidation, antimutagenesis, anti-inflammation, myeloprotection, and immunomodulation. However, since a majority of the phytochemicals have only been subjected to preclinical studies, clinical trials are imperative to comprehensively evaluate their therapeutic values. CONCLUSION: This review highlights that phytochemicals have interesting properties in relieving the side effects of chemotherapy and radiotherapy. Future studies are required to explore the clinical benefits of these phytochemicals for exploitation in chemotherapy and radiotherapy.

Degradation of Aflatoxin B1 and Zearalenone by Bacterial and Fungal Laccases in Presence of Structurally Defined Chemicals and Complex Natural Mediators.

Aflatoxin B1 (AFB1) and zearalenone (ZEN) exert deleterious effects to human and animal health. In this study, the ability of a CotA laccase from Bacillus subtilis (BsCotA) to degrade these two mycotoxins was first investigated. Among the nine structurally defined chemical compounds, methyl syringate was the most efficient mediator assisting BsCotA to degrade AFB1 (98.0%) and ZEN (100.0%). BsCotA could also use plant extracts, including the Epimedium brevicornu, Cucumis sativus L., Lavandula angustifolia, and Schizonepeta tenuifolia extracts to degrade AFB1 and ZEN. Using hydra and BLYES as indicators, it was demonstrated that the degraded products of AFB1 and ZEN using the laccase/mediator systems were detoxified. Finally, a laccase of fungal origin was also able to degrade AFB1 and ZEN in the presence of the discovered mediators. The findings shed light on the possibility of using laccases and a mediator, particularly a natural plant-derived complex mediator, to simultaneously degrade AFB1 and ZEN contaminants in food and feed.

Effects of Cinnamaldehyde on the Cell Wall of A. fumigatus and Its Application in Treating Mice with Invasive Pulmonary Aspergillosis.

BACKGROUND: The invasive pulmonary aspergillosis is a kind of high incidence of disease with difficulties in treatment, poor prognosis, and high mortality. OBJECTIVES: The study aimed to reveal the effect of cinnamaldehyde on the fungal cell wall and verify its efficacy on invasive pulmonary aspergillosis on immunosuppressed Institute of Cancer Research mice (ICR mice). METHODS: ICR mice were given cyclophosphamide 200 mg.kg-1. d-1 by intraperitoneal injection for 2 days. On the 4th day, the mice were given 50 µL of Aspergillosis fumigatus spore (107colony form unit CFU/mL) by intranasal injection to establish immunosuppressive animal models with invasive Aspergillosis fumigatus infection. Then the mice in treatment group orally administered cinnamaldehyde for 14 consecutive days, while voriconazole was given to the mice in the positive control group. RESULTS: The clearance rate of pulmonary fungi, cure rate, and reduction of 1,3-ß-D-glucans in treatment group were 80.00%, 80.00%, and 81.00%, respectively while in positive control group they were 67.00%, 60.00%, and 62.00%, respectively. There were significant differences in the results between two groups as mentioned above (P<0.05). Electron microscopy showed that, in treatment group, the cell wall of Aspergillus fumigatus was dissolved and detached and the cell surface was incomplete. There were edema, degeneration, and necrosis in nucleus and organelle, which lead to cellular necrocytosis. The cytomembrane of Aspergillus fumigatus was intact, clear, and complete, whereas the cytomembrane in the positive control group disappeared. The hyphal morphology of Aspergillus fumigatus was deformed, but the cell wall was intact. CONCLUSION: Cinnamaldehyde has a good curative effect in the treatment of invasive pulmonary aspergillus infection in immunodeficient mice. It mainly affects the synthesis of 1,3-ß-D-glucans from the cytoderm of Aspergillus fumigatus but does not affect cell wall. It would potentially be an effective and novel drug for targeted treatment of Aspergillus fumigatus deep infection.

Protective effect of Naoxintong against cerebral ischemia reperfusion injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Naoxintong (NXT), a renowned traditional Chinese medicine in China, has been used for the treatment of acute and chronic cardio-cerebrovascular diseases in clinic for more than 20 years. AIM OF THE STUDY: To evaluate the potential neuroprotective effect of NXT against ischemia reperfusion (I/R) injury in mice and investigate the underlying mechanisms. MATERIALS AND METHODS: Focal cerebral I/R injury in adult male CD-1 mice was induced by transient middle cerebral artery occlusion (tMCAO) for 1h followed by reperfusion for 23h. Mice were randomly divided into five groups: Sham group; tMCAO group; Vehicle group; NXT-treated groups at doses of 0.36g/kg and 0.54g/kg. The effects of NXT on murine neurological function were estimated by neurological defect scores, infarct volume and brain water content at 24h after tMCAO. Immunohistochemistry and Western blot were used to detect the expression of LOX-1, pERK1/2 and NF-κB at 24h after tMCAO. qRT-PCR was used to detect the expression of LOX-1 and NF-κB at 24h after tMCAO. RESULTS: Compared with Vehicle group, 0.54g/kg group of NXT significantly ameliorated neurological outcome, infarction volume and brain water content, decreased the expression of LOX-1, pERK1/2 and NF-κB (P<0.05). CONCLUSION: NXT protected the mice brain against I/R injury, and this protection maybe associated with the down-regulation of LOX-1, pERK1/2 and NF-κB expression.

Skp1 in lung cancer: clinical significance and therapeutic efficacy of its small molecule inhibitors.

Skp1 is an essential adaptor protein of the Skp1-Cul1-F-box protein complex and is able to stabilize the conformation of some ubiquitin E3 ligases. However, the role Skp1 plays during tumorigenesis remains unclear and Skp1-targeting agent is lacking. Here we showed that Skp1 was overexpressed in 36/64 (56.3%) of non-small cell lung cancers, and elevated Skp1 was associated with poor prognosis. By structure-based high-throughput virtual screening, we found some Skp1-targeting molecules including a natural compound 6-O-angeloylplenolin (6-OAP). 6-OAP bound Skp1 at sites critical to Skp1-Skp2 interaction, leading to dissociation and proteolysis of oncogenic E3 ligases NIPA, Skp2, and ß-TRCP, and accumulation of their substrates Cyclin B1, P27 and E-Cadherin. 6-OAP induced prometaphase arrest and exerted potent anti-lung cancer activity in two murine models and showed low adverse effect. These results indicate that Skp1 is critical to lung cancer pathogenesis, and Skp1 inhibitor inactivates crucial oncogenic E3 ligases and exhibits significant therapeutic potentials.

[Treatment of Urban Runoff Pollutants by a Multilayer Biofiltration System].

In order to control the non-point source pollution from road runoff in Wuxi City effectively, a multilayer biofiltration system was designed to remove a variety of pollutants according to the characteristics of road runoff in Wuxi, and the experimental research was carried out to study the effect on rainwater pollution purification. The results show that the system has a good performance on removing suspended solids (SS), organic pollutant (COD), nitrogen and phosphorus: all types of multilayer biofiltration systems have a high removal rate for SS, which can reach 90%. The system with activated carbon (GAC) has higher removal rates for COD and phosphorus. The system with zeolite (ZFM) has a relatively better removal efficiency for nitrogen. The addition of wood chips in the system can significantly improve the system efficiency for nitrogen removal. Between the two configurations of layered and distributed wood chips, configurations of distributed wood chips reach higher COD, phosphorus and nitrogen pollutants removal efficiencies since they can reduce the release of wood chips dissolution.

Analysis of EEG activity in response to binaural beats with different frequencies.

When two coherent sounds with nearly similar frequencies are presented to each ear respectively with stereo headphones, the brain integrates the two signals and produces a sensation of a third sound called binaural beat (BB). Although earlier studies showed that BB could influence behavior and cognition, common agreement on the mechanism of BB has not been reached yet. In this work, we employed Relative Power (RP), Phase Locking Value (PLV) and Cross-Mutual Information (CMI) to track EEG changes during BB stimulations. EEG signals were acquired from 13 healthy subjects. Five-minute BBs with four different frequencies were tested: delta band (1 Hz), theta band (5 Hz), alpha band (10 Hz) and beta band (20 Hz). We observed RP increase in theta and alpha bands and decrease in beta band during delta and alpha BB stimulations. RP decreased in beta band during theta BB, while RP decreased in theta band during beta BB. However, no clear brainwave entrainment effect was identified. Connectivity changes were detected following the variation of RP during BB stimulations. Our observation supports the hypothesis that BBs could affect functional brain connectivity, suggesting that the mechanism of BB-brain interaction is worth further study.

Chrysophanol inhibits NALP3 inflammasome activation and ameliorates cerebral ischemia/reperfusion in mice.

The most effective way to contain cerebral ischemic injury is reperfusion; however, reperfusion itself may result in tissue injury, for which inflammatory damage is one of the main causative factors. NALP3 inflammasome is a multiprotein complex. It consists of NALP3, ASC, and caspase-1, whose function is to switch on the inflammatory process. Chrysophanol is an extract from plants of Rheum genus and it possesses many pharmacological effects including its anti-inflammation activity. In this study, the effects of chrysophanol in cerebral ischemia/reperfusion and the potential mechanisms were investigated. Male CD1 mice were subject to transient middle cerebral artery occlusion (tMCAO). The NALP3 inflammasome activation status and its dynamic expression during the natural inflammatory response induced by tMCAO were first profiled. The neuroprotective effects of chrysophanol were then assessed and the potential mechanisms mediating the observed neuroprotection were then explored. Physical parameters including neurological deficit, infarct size, brain edema, and BBB permeability were measured at 24 h after tMCAO. Confocal microscopy, Western blotting, immunohistochemistry, and qRT-PCR techniques were utilized to analyze the expression of NALP3 inflammasome and IL-1 ß . Our results indicated that the brain tissue damage during cerebral ischemia/reperfusion is accompanied by NALP3 inflammasome activation. Chrysophanol could inhibit the activation of NALP3 inflammasome and protect cerebral ischemic stroke.

Autophagy-associated targeting pathways of natural products during cancer treatment.

It is well known that conventional chemotherapy and radiation therapy can result in toxicity to both normal cells and tumor cells, which causes limitations in the application of these therapeutic strategies for cancer control. Novel and effective therapeutic strategies for cancers with no or low toxicity for normal cells are a high priority. Therefore, natural products with anticancer activity have gained more and more attention due to their favorable safety and efficacy profiles. Pre-clinical and clinical studies have demonstrated that several representative natural compounds such as resveratrol, epigallocatechin-3-gallate, curcumin, allicin and ginsenosides have obvious anticancer potential. In this article, we summarize autophagy-associated targeting pathways of such natural products for inducing the death of cancer cells, and discuss the core autophagic pathways involved in cancer treatments. Recent advances in the discovery, evaluation and exploitation of natural compounds as therapeutic agents for cancers will provide references and support in pre-clinical and clinical application of novel natural drugs for the treatment of primary and metastatic tumors in the future.

Confirmatory factor analysis of the stagnation scale--a traditional Chinese medicine construct operationalized for mental health practice.

BACKGROUND: Traditional Chinese medicine stagnation ("yu") syndrome is characterized by a cluster of mind/body obstruction-like symptoms. Previous studies have operationalized the concept as a psychological construct through scale development, producing a three-factor 16-item inventory with good psychometric properties. PURPOSE: The study aimed to further validate the Stagnation Scale by confirmatory factor analysis (CFA) and examine self-appraisal of stagnation as an illness. METHOD: A cross-sectional questionnaire survey was conducted on a random community sample of 755 adults recruited by cluster sampling in Hong Kong. RESULTS: CFA revealed a good fit of the three-factor model (CFI = .95; RMSEA = .077; SRMR = .043). ROC analysis suggested a cutoff score at 50 on stagnation total score for predicting self-appraisal of an illness condition, with false positive and negative rates at 25.8% and 23.3%, respectively. Overall, 6.2% participants self-appraised to suffer stagnation symptoms to a degree of an illness, and for it, 1.9% participants intended to seek treatment. Stagnation showed positive correlations with physical distress, depression, and anxiety (r = .59-.76, p < .01) and negative correlation with age (r = -.22, p < .01). CONCLUSION: The Stagnation Scale appeared to be robust in factorial and construct validity. With prevalence of illness by self-appraisal at 6.2% and intention for treatment at 1.9%, stagnation is a fairly common condition associated with treatment-seeking behaviors.