Dioscin decreases M2 polarization via inhibiting a positive feedback loop between RBM47 and NF-κB in glioma.

BACKGROUND: The role of the glioblastoma (GBM) microenvironment is pivotal in the development of gliomas. Discovering drugs that can traverse the blood-brain barrier and modulate the tumor microenvironment is crucial for the treatment of GBM. Dioscin, a steroidal saponin derived from various kinds of plants and herbs known to penetrate the blood-brain barrier, has shown its powerful anti-tumor activity. However, little is known about its effects on GBM microenvironment. METHODS: Bioinformatics analysis was conducted to assess the link between GBM patients and their prognosis. Multiple techniques, including RNA sequencing, immunofluorescence staining, Western blot analysis, RNA-immunoprecipitation (RIP) assays, and Chromatin immunoprecipitation (CHIP) analysis were employed to elucidate the mechanism through which Dioscin modulates the immune microenvironment. RESULTS: Dioscin significantly impaired the polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages in vitro and in vivo. A strong correlation between high expression of RBM47 in GBM and a detrimental prognosis for patients was demonstrated. RNA-sequencing analysis revealed an association between RBM47 and the immune response. The inhibition of RBM47 significantly impaired the recruitment and polarization of macrophages into the M2 phenotype and enhanced the phagocytic ability of macrophages. Moreover, RBM47 could stabilize the mRNA of inflammatory genes and enhance the expression of these genes by activating the NF-κB pathway. In addition, NF-κB acts as a transcription factor that enhances the transcriptional activity of RBM47. Notably, we found that Dioscin could significantly inhibit the activation of NF-κB and then downregulate the expression of RBM47 and inflammatory genes protein. CONCLUSION: Our study reveals that the positive feedback loop between RBM47 and NF-κB could promote immunosuppressive microenvironment in GBM. Dioscin effectively inhibits M2 polarization in GBM by disrupting the positive feedback loop between RBM47 and NF-κB, indicating its potential therapeutic effects in GBM treatment.

BiTiS3 bio-transducer with explosive on-demand generation of NO gas for synergetic cancer therapy.

Combined photothermal therapy and nitric oxide (NO)-mediated gas therapy has shown great potential as a cancer treatment. However, the on-demand release of NO at a high concentration presents a challenge owing to the lack of an ideal bio-transducer with a high loading capacity of NO donors and sufficient energy to induce NO release. Here, we present a new 2D BiTiS3 nanosheet that is synthesized, loaded with the NO donor (BNN6), and conjugated with PEG-iRGD to produce a multifunctional bio-transducer (BNN6-BiTiS3-iRGD) for the on-demand production of NO. The BiTiS3 nanosheets not only have a high loading capacity of NO donors (750%), but also exhibit a high photothermal conversion efficiency (59.5%) after irradiation by a 1064-nm laser at 0.5 W/cm2. As a result of the above advantages, the temporal-controllable generation of NO within a large dynamic range (from 0 to 344 µM) is achieved by adjusting power densities, which is among the highest efficiency values reported for NO generators so far. Moreover, the targeted accumulation of BNN6-BiTiS3-iRGD at tumor sites leads to spatial-controllable NO release. In vitro and in vivo assessments demonstrate synergistic NO gas therapy with mild photothermal therapy based on BNN6-BiTiS3-iRGD. Our work provides insights into the design and application of other 2D nanomaterial-based therapeutic platforms.

Screening the components in multi-biological samples and the comparative pharmacokinetic study in healthy and depression model rats of Suan-Zao-Ren decoction combined with a network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Suanzaoren Decoction (SZRD) is a classic traditional Chinese prescription, which has been commonly used for treating insomnia, depression and other nerve system diseases for a long time. AIM OF THIS STUDY: The present study aimed to explore the metabolic profiles in multi-biological samples and pharmacokinetic mechanism between healthy and depression model rats combined with a network pharmacology approach after administration of SZRD. MATERIALS AND METHODS: In our study, an ultra-high performance liquid chromatography (UPLC)-Q-Exactive Orbitrap Mass Spectrometry method was firstly used to study the prototype components and metabolites of SZRD in plasma, brain, urine, and feces between healthy and depressed rats. The possible metabolic pathways were also speculated. Then a network pharmacological study was conducted on the components in the plasma of model rats. According to the above components screened by network pharmacology and the other reported representative active components, the comparative pharmacokinetic study was established for the simultaneous determination of mangiferin, spinosin, ferulic acid, liquiritin, formononetin. magnoflorine and isoliquiritin between healthy and depression model rats. Finally, molecular docking was used to validate the binding affinity between key potential targets and active components in pharmacokinetics. RESULTS: A total of 115 components were identified in healthy rats, and 101 components were identified in model rats. The prototype components and metabolites in plasma, brain, urine, and feces were also distinguished. The main metabolic pathways included phase I and phase II metabolic reactions, such as dehydrogenation, oxidation, hydroxylation, gluconaldehyde conjugation, glutathione conjugation and so on. These results provided a basis for the further study of antidepressive pharmacokinetic and pharmacological action in SZRD. Then, according to the degree value of network pharmacological study, it was predicted that 10 components and 10 core targets, which involved in the critical pathways such as neuroactive ligand-receptor interaction, cyclic adenosine monophosphate (cAMP) signaling pathway, serotonergic synapse, phosphatidylinositol-3 kinase (PI3K)-Akt signaling pathway, etc. Finally, the established pharmacokinetic method was successfully applied to compare the pharmacokinetic behavior of these 7 active components in plasma of healthy and depressed rats after oral administration of SZRD. It showed that except magnoflorine, the pharmacokinetic parameters of each component were different between healthy and depressed rats. Molecular docking analysis also indicated that the active compounds in pharmacokinetics could bind tightly to the key targets of network pharmacological study. CONCLUSION: This study may provide important information for studying the action mechanism of SZRD in treating depression.

Effect of the Timing of Hyperbaric Oxygen Therapy on the Prognosis of Patients with Idiopathic Sudden Sensorineural Hearing Loss.

This study aimed to evaluate the effects of hyperbaric oxygen therapy (HBOT) on the hearing recovery of patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The clinical data of 79 patients diagnosed with ISSNHL and treated with HBOT between January 2017 and December 2019 were retrospectively reviewed. The pure tone audiometry (PTA) scores before and after HBOT were recorded. The associations of HBOT efficacy with demographic and clinical characteristics and the duration from disease onset to HBOT administration were determined. The average PTA score was 80.06 ± 25.94 dB before and 60.75 ± 21.26 dB after HBOT; the difference was significant. HBOT improved the hearing of 55.7% of the patients with ISSNHL (defined as an average PTA ≥ 11dB or a final average PTA score below 29 dB). There was a significant inverse relationship between the duration from symptom onset to HBOT administration and PTA score reduction after HBOT, which was adjusted for factors including age, sex, laterality of hearing loss, initial PTA score, reception of intratympanic steroid injections, tinnitus, dizziness, vertigo, diabetes, hypertension, and coronary artery disease. Commencing HBOT at an earlier stage is closely linked to greater improvements in hearing for patients with ISSNHL.

Synthesis of germanium/germanium phosphide in-plane heterostructure with efficient photothermal and enhanced photodynamic effects in the second near-infrared biowindow.

Inspired by the bifunctional phototherapy agents (PTAs), constructing compact PTAs with efficient photothermal therapy (PTT) and photodynamic therapy (PDT) effects in the near-infrared (NIR-II) biowindow is crucial for high therapeutic efficacy. Herein, none-layered germanium (Ge) is transformed to layered Ge/germanium phosphide (Ge/GeP) structure, and a novel two-dimensional sheet-like compact S-scheme Ge/GeP in-plane heterostructure with a large extinction coefficient of 15.66 L/g cm-1 at 1,064 nm is designed and demonstrated. In addition to the outstanding photothermal effects, biocompatibility and degradability, type I and type II PDT effects are activated by a single laser. Furthermore, enhanced reactive oxygen species generation under longer wavelength NIR laser irradiation is achieved, and production of singlet oxygen and superoxide radical upon 1,064 nm laser irradiation is more than double that under 660 nm laser irradiation. The S-scheme charge transfer mechanism between Ge and GeP, is demonstrated by photo-irradiated Kelvin probe force microscopy and electron spin resonance analysis. Thus, the obtained S-scheme Ge/GeP in-plane heterostructure shows synergistic therapeutic effects of PTT/PDT both in vitro and in vivo in the NIR-II biowindow and the novel nanoplatform with excellent properties has large clinical potential.

Intervention study of tai chi training on the intestinal flora of college student basketball players.

BACKGROUND: In recent years, the interactions between host and host-associated gut flora have received increasingly widespread attention. Tai chi is a traditional Chinese exercise, which can significantly benefit adults with health condition. But the studies on the function of intestinal flora and its correlation with tai chi exercise, are limited. In addition, the influence of tai chi on intestinal flora has largely been understudied. In this study, we investigated the changes in intestinal microflora by 16S rRNA sequencing to clarify the specific mechanism of tai chi on the regulation of intestinal flora and seek to formulate a reasonable "exercise prescription." METHODS: Design: randomized controlled trial. Participants: thirty college basketball players randomly divided into control (n = 15) and test (n = 15) groups. Intervention: experimental group practiced 24-style simplified tai chi ≥ 6 times/week for 20 weeks. Outcomes: serum biochemical markers, blood pressure, and intestinal microbial composition measured post-intervention. Analysis: intent-to-treat analysis. RESULTS: Primary outcomes: after tai chi intervention, the level of high-density lipoprotein cholesterol (1.22 mmol/L) and triglycerides (0.64 mmol/L) were significantly decreased. Secondary outcomes: aspartate transaminase, alanine aminotransferase, total cholesterol, and low-density lipoprotein remained unchanged. Microbiota: α-diversity index significantly increased, particularly with increased Blautia. Blood pressure: test group showed significantly lower diastolic blood pressure (83-95 mm Hg) compared to control. DISCUSSION: Considering other markers, increased gut flora diversity during exercise may imply a healthier gut environment. Physical exercise promotes a decrease in the inflammatory process by reducing the levels of bacteria associated with pro-inflammation, such as Proteobacteria. Further research is required to understand the nuanced link between gut flora diversity and exercise intensity. CONCLUSION: 24-style simplified tai chi enhances human intestinal flora diversity. Improvements observed in blood lipid profiles and blood pressure levels.

Mesoporous carbon nanoenzyme as nano-booster for photothermal-enhanced photodynamic therapy compared with graphene oxide.

The over-expressed GSH in tumor microenvironment significantly weakens the lethal reactive oxygen species (ROS) generated by photodynamic therapy (PDT) and catalysis of nanoenzyme. Hence, it is necessary to excavate a versatile and effective vehicle with oxidative stress-enhancement and GSH-depletion capacity to break the redox homeostasis in tumor microenvironment. GO has been reported to possess GSH-depletion and peroxidase (POD)-like capacity. Based on this, PEGylated mesoporous carbon (MC-PEG) was prepared as ICG vehicle to compare with PEGylated graphene oxide (GO-PEG). Excitingly, MC-PEG was found to exhibit three times higher oxidative capacity by POD-like process than GO-PEG, and owned more effective and continuous GSH-depletion capacity to further amplify the oxidative stress. Meanwhile, MC-PEG exhibited better protective effect on the loaded ICG against unwanted light excitation than GO-PEG. Together with the higher photothermal conversion effect, under the NIR light irradiation, MC-PEG could markedly improve the temperature of tumor cells and produce more hydroxyl radical, continuously consume GSH and provide more better protection for ICG compared with GO-PEG, thus further boosting the combination of photothermal and photodynamic effects. The anti-tumor experiment in cell and in-vivo level both validated that ICG/MC-PEG showed better synergistic effect with lower IC50 value and higher tumor suppression rate than ICG/GO-PEG.

Extraction, Composition, and Antioxidant Activity of Flavonoids from Xanthoceras sorbifolium Bunge Leaves.

BACKGROUND: Xanthoceras sorbifolium Bunge leaves (XLs) are valuable resources rich in phytochemicals, especially in flavonoids, but they are rarely exploited and utilized. OBJECTIVE: The purpose of this paper is to reduce the waste of XLs resources (usually used as agricultural waste) and extract the high added value of active ingredients from XLs. METHODS: The extraction of flavonoids from XLs using ultrasonic-assisted extraction (UAE) was reported. Response surface methodology (RSM) was used to adopt different ultrasonic conditions such as ethanol concentration, liquid:solid ratio, and ultrasonic power. In addition, the chemical structures were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and HPLC. RESULTS: Response surface analysis indicated the optimal level of ethanol concentration, liquid:solid ratio, and ultrasonic power as 71.49%, 13.87 mL/g, and 157.49 W respectively for the maximum response of total flavonoids (5.52 ± 0.23%), which fitted well with the predicted value (5.68 ± 0.17%). In addition, the extracts from XLs exhibited potent antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt (ABTS). CONCLUSION: The potent antioxidant activity of flavonoids from XLs is beneficial for their application in the food and drug industry, which will facilitate the rise of the added value of the flavonoids from XLs. HIGHLIGHTS: Myricetin, rutin, and epicatechin, which may be responsible for the antioxidant activity of the extracts from XLs, were confirmed by UPLC-MS/MS and HPLC analysis. The extracted flavonoids can be used as a natural antioxidant additive to food products.

Fabricating Black-Phosphorus/Iron-Tetraphosphide Heterostructure via a Solid-Phase Solution-Precipitation Method for High-Performance Nitrogen Reduction.

Although constructing heterostructures is considered as one of the most successful strategies to improve the activity of a catalyst, the heterostructures usually suffer from the cumbersome preparation treatments and low-yield. Inspired by a solid-phase solution-precipitation (SPSP) process, an approach for interface intensive heterostructures with high yield is developed. Herein, a black-phosphorus/iron-tetraphosphide (BP/FeP4 ) heterostructure is prepared mechanochemically with high transient pressure by the solid-phase ball milling approach. The BP/FeP4 heterostructure delivers excellent catalytic performance in the nitrogen reduction reaction (NRR) as exemplified by an NH3 yield of 77.6 µg h-1 mg cat . - 1 \[{\rm{mg}}_{{\rm{cat}}{\rm{.}}}^{{\bm{ - }}1}\] and Faradic efficiency of 62.9% (-0.2 V), which are superior to that of most NRR catalysts recently reported. Experimental investigation and density-functional theory calculation indicate the importance of excess phosphorus in the heterostructures on the NRR activity, which assists the Fe atom to activate N2 via adsorbing the H atom. The results demonstrate the great potential of this new type of heterostructures prepared by the SPSP approach. Benefiting from the simple preparation process and low cost, the heterostructures offer a new insight into the development of highly efficient catalysts.

Traditional uses, phytochemistry, pharmacology and current uses of underutilized Xanthoceras sorbifolium bunge: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The Plant Xanthoceras sorbifolium Bunge (X. sorbifolia) has a long history of medicinal use as a traditional Chinese herbal medicine to deal with sterilizing, killing sperm, stabilizing capillary, hemostasis, lowering cholesterol, rheumatism, and pediatric enuresis. Additionally, X. sorbifolia is an oil crop for the production of edible oil due to the health-promotion effect. In recent years, X. sorbifolia has attracted worldwide attention as an important economic crop with low investment and high-income potential. AIM OF THE REVIEW: This review aims to provide a comprehensive appraisal of X. sorbifolia, including the traditional uses, nutrients, phytochemical data, biological activities, and current applications. The natural compounds of X. sorbifolia and potential utilization in pharmacology are highlighted. The aim of this review is to inspire the research enthusiasm to X. sorbifolia and promote the comprehensive utilization of X. sorbifolia. MATERIALS AND METHODS: The research information of X. sorbifolia was collected via Elsevier, American Chemical Society (ACS), PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu scholar, and Google scholar. Additionally, some information was collected from Ph.D. and Master's dissertations, as well as local books. RESULTS: The identification of approximately 195 major phytochemical compounds from different parts of X. sorbifolia is presented in this review, including triterpenoids, flavonoids, phenolic acids, coumarins, lignans, meroterpenoids, monoterpene, alkaloids, and sterol. Among them, triterpenoids, flavonoids, and phenolic acids are the major compounds. Extracts from X. sorbifolia exhibited a wide range of biological activities, such as antioxidant, antibacterial, anti-tumor, anti-neuroinflammatory, anti-adipogenesis, anti-obesity, anti-HIV, gastroprotective, immunoregulatory, and anti-inflammatory activities. CONCLUSIONS: Modern pharmacological studies have been well supported and clarified the traditional medicinal uses of X. sorbifolia, which brought a promising prospect for the pharmaceutical value of this plant. However, the related mechanisms between the structure and pharmacological effects were seldom reported. Also, at present, effective and in-depth research on X. sorbifolia is still relatively lacking. Moreover, there is little research on toxicological experiments. Further clinical trials should also be performed to accelerate the drug research and development.

Age-dependent alteration in metabolism of vitamin B6 , neurotransmitters, and amino acids after 4'-O-methylpyridoxine administration in rats.

4'-O-methylpyridoxine (MPN), a recognized antivitamin B6 compound, is a potentially poisonous substance found in Ginkgo biloba L. In this work, the effects of MPN on the metabolism of vitamin B6 , neurotransmitters, and amino acids were compared in the plasma and brain of young and adult rats under various administration times. Results showed that the contents of MPN residues in the plasma and brain of young rats were 12.72 and 14.76 µM higher than adult rats, respectively. Moreover, the levels of 5-hydroxytryptamine and dopamine in the brain of young rats have decreased by 13.78% and 7.19%, respectively, compared with the control group, at 2 h after MPN administration. Furthermore, the principal component analysis revealed that MPN was an important contributor to the amino acid composition in the brain of young rats. These results suggest that age may lead to different toxic effects of MPN. PRACTICAL APPLICATION: 4'-O-methylpyridoxine is primarily responsible for poisoning due to overconsumption of Ginkgo biloba seeds. This study will provide an exploratory understanding of the age-dependent toxicity of 4'-O-methylpyridoxine.

Tetrahydropalmatine Alleviates Hyperlipidemia by Regulating Lipid Peroxidation, Endoplasmic Reticulum Stress, and Inflammasome Activation by Inhibiting the TLR4-NF-κB Pathway.

Hyperlipidemia (HLP) is a lipid metabolism disorder that can induce a series of cardiovascular and cerebrovascular diseases, such as atherosclerosis, myocardial infarction, coronary heart disease, and stroke, which seriously threaten human health. Tetrahydropalmatine (THP) is a component of the plant Rhizoma corydalis and has been shown to exert hepatoprotective and anti-inflammatory effects in HLP. However, whether THP regulates lipid peroxidation in hyperlipidemia, endoplasmic reticulum (ER) stress and inflammasome activation and even the underlying protective mechanism against HLP remain unclear. An animal model of HLP was established by feeding a high-fat diet to golden hamsters. Our results showed that THP reduced the body weight and adipose index; decreased the serum content of ALT, AST, TC, TG, and LDL-C; decreased the free fatty acid hepatic lipid content (liver index, TC, TG, and free fatty acid); inhibited oxidative stress and lipid peroxidation; extenuated hepatic steatosis; and inhibited ER stress and inflammasome activation in high-fat diet-fed golden hamsters. In addition, for the first time, the potential mechanism by which THP protects against HLP through the TLR4-NF-κB signaling pathway was demonstrated. In conclusion, these data indicate that THP attenuates HLP through a variety of effects, including antioxidative stress, anti-ER stress, and anti-inflammatory effects. In addition, THP also inhibited the TLR4-NF-κB signaling pathway in golden hamsters.

In vivo toxicity assessment of 4'-O-methylpyridoxine from Ginkgo biloba seeds: Growth, hematology, metabolism, and oxidative parameters.

4'-O-methylpyridoxine (MPN), a recognized antivitamin B6 compound, is a potentially poisonous substance found in Ginkgo biloba seeds and leaves. In this work, the body weights, histopathological changes, plasma vitamin B6 (VB6), biochemical parameters, oxidative stress responses, and amino acids of rats were investigated after intragastric administration of MPN for 15 days. Results showed that intragastric administration of 50 mg/kg BW MPN caused pathological changes in the brain and heart tissues of rats. Administration of 10 mg/kg and 30 mg/kg BW MPN can significantly increase VB6 analogs in the plasma of rats, such as pyridoxal-5'-phosphate, pyridoxal. Results of biochemical parameters indicated that MPN can damage brains and hearts by changing the enzyme activity of these organs. These results suggest that consumption of Ginkgo biloba seeds for the long term, even in a small quantity, may lead to poisoning.

4'-O-methylpyridoxine: Preparation from Ginkgo biloba Seeds and Cytotoxicity in GES-1 Cells.

Ginkgo biloba seeds are wildly used in the food and medicine industry. It has been found that 4'-O-methylpyridoxine (MPN) is responsible for the poisoning caused by G. biloba seeds. The objective of this study was to explore and optimize the extraction method of MPN from G. biloba seeds, and investigate its toxic effect on human gastric epithelial cells (GES-1) and the potential related mechanisms. The results showed that the extraction amount of MPN was 1.933 µg/mg, when extracted at 40 °C for 100 min, with the solid-liquid ratio at 1:10. MPN inhibited the proliferation of GES-1 cells, for which the inhibition rate was 38.27% when the concentration of MPN was 100 µM, and the IC50 value was 127.80 µM; meanwhile, the cell cycle was arrested in G2 phase. High concentration of MPN (100 µM) had significant effects on the nucleus of GES-1 cells, and the proportion of apoptotic cells reached 43.80%. Furthermore, the Western blotting analysis showed that MPN could reduce mitochondrial membrane potential by increasing the expression levels of apoptotic proteins Caspase 8 and Bax in GES-1 cells. In conclusion, MPN may induce apoptosis in GES-1 cells, which leads to toxicity in the human body.

A multi-institutional retrospective study of hyperthermic plus intravesical chemotherapy versus intravesical chemotherapy treatment alone in intermediate and high risk nonmuscle-invasive bladder cancer.

Objective: To compare the efficacy and safety of hyperthermic intravesical chemotherapy (HIVEC) and intravesical chemotherapy (IVEC) in patients with intermediate and high risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection. Methods: We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers. We matched 364 intermediate or high risk cases and divided them into 2 groups: the HIVEC+IVEC group [chemohyperthermia (CHT) composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia] and the IVEC group (intravesical instillation without hyperthermia). The data were recorded in the database. The primary endpoint was 2-year recurrence-free survival (RFS) in all NMIBC patients (n = 364), whereas the secondary endpoints were the assessment of radical cystectomy (RC) and 5-year overall survival (OS). Results: There was a significant difference in the 2-year RFS between the two groups in all patients (n = 364; HIVEC+IVEC: 82.42% vs. IVEC: 74.18%, P = 0.038). Compared with the IVEC group, the HIVEC+IVEC group had a lower incidence of RC (P = 0.0274). However, the 5-year OS was the same between the 2 groups (P = 0.1434). Adverse events (AEs) occurred in 32.7% of all patients, but none of the events was serious (grades 3-4). No difference in the incidence or severity of AEs between each treatment modality was observed. Conclusions: This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients. Both treatments were well-tolerated in a similar manner.

Saccharogenic refining of Ginkgo biloba leaf residues using a cost-effective enzyme cocktail prepared by the fungal strain A32 isolated from ancient ginkgo biloba tree.

To reduce environmental pollution and waste of biomass from Ginkgo biloba leaf residues (GBLRs), we developed a cost-effective enzyme system to hydrolyze GBLRs into available reducing sugars (RS). Biomass characteristics of GBLRs were investigated, which indicated that the acid hydrolyzed fraction was 49.43% of the dry weight of GBLRs. The fraction could be effectively converted into RS by an enzyme cocktail with high polygalacturonase activity without traditionally intricate pretreatment. The strain A32 isolated from the ancient ginkgo soil was used for the production of the enzyme cocktail, and a response surface methodology was used to optimize the enzymatic production. The enzyme cocktail released 87.2% of RS from GBLRs at 35 â„ƒ for 72 h with 1% (m/v) of loading, and the RS concentration arrived 8.95 ± 0.39 mg/ml with 9% of GBLRs loading. The cost-effective system of self-prepared enzyme cocktail is promising for facilitating GBLRs' bio-based industry.

Brain metabolomics study for the protective effects of Rhodiola crenulata extract on Alzheimer's disease by HPLC coupled with Fourier transform-ion cyclotron resonance mass spectrometry.

In order to investigate the protective effects of Rhodiola crenulata extract on Alzheimer's disease, a brain metabolomics study in rats was conducted by high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry. Rat model was constructed by bilateral hippocampal injection of amyloid-ß peptide and immunohistochemistry was performed to evaluate the pharmacological effect of Rhodiola crenulata extract. Multivariate statistical analysis was used to discover potential biomarkers in rat brain and related metabolic pathways analysis was conducted to elucidate the action mechanism of Rhodiola crenulata extract. As a result, a total of 19 metabolites contributing to Alzheimer's disease progress were identified and nine of them were restored to the normal levels after drug administration. Pathway analysis revealed that the protective effects of Rhodiola crenulata extract are related to the regulation of glutathione metabolism and arachidonic acid metabolism in rat brain. In conclusion, this work demonstrates that the developed metabolomics method is useful to investigate the protective effects of Rhodiola crenulata extract against Alzheimer's disease. These outcomes may further provide reliable evidence to illuminate the intervention mechanism of other traditional Chinese medicines on Alzheimer's disease.

Effects of dietary fish meal replacement by fermented moringa (Moringa oleifera Lam.) leaves on growth performance, nonspecific immunity and disease resistance against Aeromonas hydrophila in juvenile gibel carp (Carassius auratus gibelio var. CAS III).

This study was aimed to evaluate the effects of partial replacement of fish meal by fermented moringa leaves (FMLs) on growth performance, serum biochemistry, antioxidant status, nonspecific immunity, and resistance against Aeromonas hydrophila in juvenile gibel carp (Carassius auratus gibelio var. CAS III). Four isonitrogenous and isoenergetic balanced diets, including three FML diets (substituting 20%, 40%, 60% of the fish meal in basal diet, F20, F40 and F60, respectively) and a basal diet (a diet containing 10% fish meal) were used. Each diet was randomly allocated to four fish groups (F20, F40, F60 and control) reared in a recirculating system. After 50 days of the feeding trial, fish were challenged by A. hydrophila. The result revealed that final mean body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), feed efficiency (FE) and survival rate (SR) were significantly increased (P < 0.05) in F20 and F40 groups compared with the control group. Decreased hepatosomatic index (HSI), body crude lipid, serum aspartate transaminase (AST) and serum alanine aminotransferase (ALT) activities, and increased serum alkaline phosphatase (AKP) and serum glutathione peroxidase (GPx) activities were observed in F40 and F60 groups compared with the control and F20 groups. All FMLs-supplemented groups increased (P < 0.05) serum superoxide dismutase (SOD), catalase (CAT) and lysozyme activities, complement component 3 (C3) and serum immunoglobulin M (IgM) concentration, or decreased serum malondialdehyde (MDA) and protein carbonyl (PCC) contents (P < 0.05). After the challenge test, the significant downregulation of toll-like receptors2 (TLR2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-8 mRNA transcription levels was observed in spleens of FMLs supplemented groups. Dietary F40 and F60 showed higher (P < 0.05) relative percent survival (RPS) (48.72% and 43.59%, respectively) against A. hydrophila infection than control. These results indicate that, as a dietary fish meal substitute, FMLs enhance the growth, and antioxidant and immune response, and regulate the expression of immune-related genes and increase disease resistance against A. hydrophila via TLR2 pathway in gibel carp, with greatest effects of 40% fish meal substitution.

Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer's Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway.

Alzheimer's disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aß 25-35 and D-gal-induced AD rats and Aß 25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aß 25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.

Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer's Disease Based on Systems Biology.

Kai-Xin-San (KXS), a classical Chinese traditional prescription, was widely applied in the treatment of Alzheimer's disease (AD), while its functional mechanisms still remain unclear. By using systems biology approaches at animal, cellular, and molecular levels, the improvement of KXS on cognitive impairment was achieved by inhibiting abnormal acetylcholinesterase. The function on the nerve skeleton was performed by regulating the Tau phosphorylation pathway. Its antioxidant, anti-inflammatory, and antiapoptotic effects by modulating the aberrant upregulation of ROS, proinflammatory factors, and apoptosis-related proteins in the brain were studied to reveal the synergistic therapeutic efficacy of KXS. Then, formula dismantling in vitro indicated that ginseng was the principal herb, whereas three other herbs served adjuvant roles to achieve the best effect. After that, the in vivo analysis of components into plasma and brain of AD rats showed that 8 of 23 components in blood and 4 of 10 components in brain were from ginseng, respectively, further verifying the principal status of ginseng and the synergistic effects of the formula. Thus, the anti-AD effects of KXS were achieved by multitargets and multichannels. The systems biology approaches presented here provide a novel way in traditional herbal medicine research.