Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking.

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.

Metabolomic and Transcriptomic Analysis of Effects of Three MUFA-Rich Oils on Hepatic Glucose and Lipid Metabolism in Mice.

SCOPE: Olive oil, rapeseed oil, and lard are dietary fats rich in monounsaturated fatty acids, but the effects of dietary oils enriched in monounsaturated fatty acids on hepatic lipid deposition have seldom been compared. METHODS AND RESULTS: Ninety 8-week-old C57BL/6J male mice are randomly divided into six groups and fed diets containing lard, rapeseed oil, or olive oil with a 10% or 45% fat energy supply for 16 weeks. Under high-fat conditions, serum total cholesterol levels in the lard and olive oil groups are significantly higher than those in the rapeseed oil group. Hepatic lipid content in the olive oil group is higher than that in the other two groups. Compared with rapeseed oil, lard increases the liver levels of arachidonic, palmitic, and myristic acids and decreases the levels of eicosapentaenoic linolenic acid and linoleic acid. Olive oil increases the liver levels of docosatrienoic, arachidonic, oleic, and myristic acids; maltose; and fructose and decreases the levels of eicosapentaenoic, linolenic, and linoleic acids. CONCLUSION: Olive oil probably causes hepatic lipid deposition in mice, which may enhance hepatic lipid synthesis by activating the starch and sucrose metabolic pathways. By contrast, rapeseed oil shows a significant anti-lipid deposition effect on the liver.

Effects of anti-stress agents on the growth performance and immune function in broiler chickens with vaccination-induced stress.

The aim of this study was to evaluate the effects of anti-stress agents on the growth performance and immune function of broilers under immune stress conditions induced by vaccination. A total of 128, 1-day-old Arbor Acres broilers were randomly divided into four groups. Group normal control (NC) was the control group. Group vaccination control (VC), T 0.5%, and T 1% were the treatment groups, which were nasally vaccinated with two doses of the Newcastle disease virus (NDV) vaccine. The chicks in groups T 0.5% and T 1% were fed conventional diets containing 0.5% and 1% anti-stress agents. Thereafter, these broilers were slaughtered on 1, 7, 14, and 21 days post-vaccination. The results indicated that anti-stress agents could significantly reduce serum adrenocorticotropic hormone (ACTH) (P < 0.01) and cortisol (CORT) (P < 0.05) levels, and improve the growth performance (P < 0.05) and immune function of broilers (P < 0.05); However, the levels of malondialdehyde (MDA) (P < 0.05) were decreased, and the decreased total antioxidant capacity (T-AOC) (P < 0.01) levels mediated by vaccination were markedly improved. In addition, anti-stress agents could attenuate apoptosis in spleen lymphocytes (P < 0.01) by upregulating the ratio of Bcl-2 to BAX (P < 0.01) and downregulating the expression of caspase-3 and -9 (P < 0.01), which might be attributed to the inhibition of the enzymatic activities of caspase-3 and -9 (P < 0.05). In conclusion, anti-stress agents may improve growth performance and immune function in broilers under immune-stress conditions.RESEARCH HIGHLIGHTS Investigation of effects and mechanism of immune stress induced by vaccination.Beneficial effect of anti-stress agents on growth performance, immune function, oxidative stress, and regulation of lymphocyte apoptosis.Demonstration of the effects of apoptosis on immune function in the organism.

High lignin, light-driven shape memory polymers with excellent mechanical performance.

With the gradual global standardization of carbon emission policies, the development of renewable resources to replace traditional fossil resources is assuming increasing importance. Lignin is the most abundant natural source of aromatic compounds and has the potential to replace petroleum-based aromatic hydrocarbons. In this work, the rigid benzene ring structure and excellent photothermal properties of lignin were exploited to produce light-driven lignin-based shape memory polymers (ELEPs) that contain high proportions of lignin and have good mechanical properties. Enzymatically hydrolyzed lignin (EL), epoxy soybean oil (ESO) and polyethylene glycol (PEG 400) were copolymerized and cured to form ELEPs, which have a disordered three-dimensional network. An increase in the proportion of EL from 40 to 60 wt% enhanced the mechanical properties, as reflected by an increase in tensile strength from 11.3 to 30.8 MPa and in the glass transition temperature (Tg) from 93 to 115.7 °C. Under simulated solar irradiation (2000 W m-2), ELEP50, which contains 50 wt% lignin and has a Tg of 105 °C, reached a surface temperature as high as 105 °C and achieved shape memory within 20 s. The shape fixation ratio (Rf) and shape recovery ratio (Rr) were stably >98 % and >97 %, respectively, over eight cycles in a bending-recovery experiment. The unique light-driven shape memory properties of ELEPs provide a method for high value utilization of EL, and the design strategy offers new ideas for producing novel intelligent materials.

Exploration of suitable in vitro simulated digestion model for lipid oxidation of flaxseed oil emulsion during digestion.

BACKGROUND: The INFOGEST model is a standardized general in vitro digestion study, but it cannot accurately simulate the fatty acid release process of lipids in the stomach and small intestine. In this study, the internationally universal INFOGEST 2019 was used as the basic model and flaxseed oil emulsion was used as the research object. In various improvement models, the effect of fatty acid release rate on the oxidation stability of flaxseed oil was assessed by adding rabbit stomach extract and changing the order of bile salts addition. RESULTS: With the presence of rabbit gastric extract, flaxseed oil emulsion flocculation and coalescence in stomach were reduced, and the absolute value of ζ-potential increased. Moreover, the release rate of fatty acids in the small intestine increased by 12.14%. The amount of lipid oxidation product (i.e. hexanal) in the gastric and intestinal phases increased by 0.08 ppb. In addition, the fatty acid release rate in the small intestine phase increased by 5.85% and the hexanal content increased by 0.011 ppb in the digestion model of adding bile salts before adjusting the pH in the small intestine phase compared with the model of adjusting the pH first and then adding bile salts. CONCLUSION: The results obtained from this study will contribute to finding the most suitable static digestion model for simulating digestion and oxidation of lipid during lipid gastrointestinal digestion. © 2022 Society of Chemical Industry.

A Lard and Soybean Oil Mixture Alleviates Low-Fat-High-Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

Dietary habit is highly related to nonalcoholic fatty liver disease (NAFLD). Low-fat-high-carbohydrate (LFHC) diets could induce lean NAFLD in Asians. Previously, we found that a lard and soybean oil mixture reduced fat accumulation with a medium-fat diet; therefore, in this study, we evaluated the effect of a lard and soybean oil mixture (LFHC diet) on NAFLD and its underlying mechanisms. Mice in groups were fed with lard, soybean oil, or a lard and soybean oil mixture-an LFHC diet-separately. Our results showed that mixed oil significantly inhibited serum triglyceride, liver triglyceride, serum free fatty acids (FFAs), and liver FFAs compared with soybean oil or lard, and we found fewer inflammatory cells in mice fed with mixed oil. RNA-seq results indicate that mixed oil reduced FFAs transportation into the liver via decreasing liver fatty acid-binding protein 2 expression, inhibited oxidative phosphorylation via tumor necrosis factor receptor superfamily member 6 downregulation, and alleviated inflammation via downregulating inflammatory cytokine. The liquid chromatography-mass spectrometry results showed that the mixed oil promoted bile acid conjugated with taurine and glycine, thus activating G-protein-coupled bile acid receptor 1 for improved lipids metabolism. In conclusion, the lard and soybean oil mixture alleviated NAFLD.

Mixture of Five Fermented Herbs (Zhihuasi Tk) Alters the Intestinal Microbiota and Promotes the Growth Performance in Piglets.

To explore the feasibility of using fermented Chinese herbal mixture Zhihuasi Tk (Z. Tk) supplementation to increase the swine production, the protective effect of dietary supplementation with Z. Tk on the intestinal oxidative stress model and the regulation of both growth performance and intestinal microbiota of weaned piglets were investigated in vitro. Our results showed that the addition of Z. Tk increased the cell viability, prevented the decrease of glutathione peroxidase, and significantly increased the total antioxidant capacity and reduced the damage caused by H2O2 to the tight junction proteins of the porcine small intestinal epithelial cell line (IPEC-J2). Furthermore, weaned piglets supplemented with either 2 kg/ton zinc oxide (ZnO) or 4 kg/ton of Z. Tk in the diet increased body weight as well as average daily feed intake and daily gain, while the feed conversion rate and diarrhea rate decreased within 0-35 days. Results of the taxonomic structure of the intestinal microbiota showed that, in 21 days after weaning, the Firmicutes/Bacteroidetes ratio in experimental group was increased, while the abundance of beneficial bacteria such, as Lactobacillus, was increased by Z. Tk, showing inhibitory effect on pathogenic bacteria such as members of Proteobacteria. In summary, dietary supplementation with Z. Tk maintained the intestinal microbiota in a favorable state for the host to effectively reduce the abnormal changes in the intestinal microbial structure and improved growth performance of weaned piglets. Therefore, Z. Tk may potentially function as a substitute for ZnO in feed additives for weaned piglets in modern husbandry.

Effects of cannabinoid (CBD) on blood brain barrier permeability after brain injury in rats.

Cannabidiol is a natural herbal medicine known to protect the brain from traumatic brain injury (TBI). Here, a TBI rat model was established, with cannabidiol administered intraperitoneally at doses of 5, 10, or 20 mg/kg, 30 min before surgery and 6 h after surgery until sacrifice. Brain water content, body weight, and modified neurological severity scores were determined, and enzyme-linked immunosorbent assay, immunofluorescence staining, hematoxylin and eosin staining, Nissl staining, Evans-blue dye extravasation, and western blotting were performed. Results showed that cannabidiol decreased the number of aquaporin-4-positive and glial fibrillary acidic protein-positive cells. Cannabidiol also significantly reduced the protein levels of proinflammatory cytokines (TNF-α and IL-1ß) and significantly increased the expression of tight junction proteins (claudin-5 and occludin). Moreover, cannabidiol administration significantly mitigated water content in the brain after TBI and blood-brain barrier disruption and ameliorated the neurological deficit score after TBI. Cannabidiol administration improved the integrity and permeability of the blood-brain barrier and reduced edema in the brain after TBI.

Blooms of diatom and dinoflagellate associated with nutrient imbalance driven by cycling of nitrogen and phosphorus in anaerobic sediments in Johor Strait (Malaysia).

Coastal eutrophication is one of the pivotal factors driving occurrence of harmful algal blooms (HABs), whose underlying mechanism remained unclear. To better understand the nutrient regime triggering HABs and their formation process, the phytoplankton composition and its response to varying nitrogen (N) and phosphorus (P), physio-chemical parameters in water and sediment in Johor Strait in March 2019 were analyzed. Surface and sub-surface HABs were observed with the main causative species of Skeletonema, Chaetoceros and Karlodinium. The ecophysiological responses of Skeletonema to the low ambient N/P ratio such as secreting alkaline phosphatase, regulating cell morphology (volume; surface area/volume ratio) might play an important role in dominating the community. Anaerobic sediment iron-bound P release and simultaneous N removal by denitrification and anammox, shaped the stoichiometry of N and P in water column. The decrease of N/P ratio might shift the phytoplankton community into the dominance of HABs causative diatoms and dinoflagellates.

Community composition and functional genes explain different ecological roles of heterotrophic bacteria attached to two bloom-forming cyanobacterial genera.

Eutrophication leads to frequent outbreaks of cyanobacterial blooms, however, the effect of heterotrophic bacteria attached to cyanobacterial cells is unclear. Field investigations were carried out to gain a deeper understanding of the community composition and functional role of heterotrophic bacteria attached to Dolichospermum and Microcystins cells. The significantly positive relationships between Dolichospermum density and total nitrogen (TN) and between Microcystins density and particle nitrogen (PN) indicated the strong nitrogen (N) demand of these two species. The lack of functional genes that mediate the nitrification process in bacteria attached to both Microcystins and Dolichospermum cells indicated that these two genera preferred ammonium (NH4+-N). Dolichospermum cells obtained more available N through N2 fixation, which was expressed by high nitrogenase gene abundance. Bacteria attached to Microcystins cells showed a higher activity of leucine aminopeptidase and a significantly higher abundance of functional genes that mediate dissimilatory nitrate reduction to ammonium (DNRA) than those attached to Dolichospermum cells. The significantly higher abundance of carbon degradation genes and ß-glucosidase activity of bacteria attached to Microcystins cells compared with those of bacteria attached to Dolichospermum cells suggested that abundant organic carbon was bound to Microcystins cells, which is a prerequisite for DNRA. In addition, Microcystins cells exhibited a great advantage in soluble reactive phosphorus (SRP) production through high levels of organic phosphorus (P) hydrolysis associated with high levels of phosphatase genes of attached bacteria. In conclusion, bacteria attached to Microcystins cells performed more important functions on NH4+-N and SRP production through ammonification and DNRA, as well as phosphatase hydrolysis respectively, compared to those attached to Dolichospermum. Thus, algal growth is the result of different variables such as nutrient concentration, their ratio and the microbial ability.

Acute EPA-induced learning and memory impairment in mice is prevented by DHA.

Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been widely used to prevent cardiovascular disease (CVD) and treat brain diseases alone or in combination with docosahexaenoic acid (DHA). However, the impact of EPA and DHA supplementation on normal cognitive function and the molecular targets of EPA and DHA are still unknown. We show that acute administration of EPA impairs learning and memory and hippocampal LTP in adult and prepubescent mice. Similar deficits are duplicated by endogenously elevating EPA in the hippocampus in the transgenic fat-1 mouse. Furthermore, the damaging effects of EPA are mediated through enhancing GABAergic transmission via the 5-HT6R. Interestingly, DHA can prevent EPA-induced impairments at a ratio of EPA to DHA similar to that in marine fish oil via the 5-HT2CR. We conclude that EPA exhibits an unexpected detrimental impact on cognitive functions, suggesting that caution must be exercised in omega-3 fatty acid supplementation and the combination of EPA and DHA at a natural ratio is critical for learning and memory and synaptic plasticity.

Construction of synergistic therapy system with multiple therapeutic effects based on CuS@Tf nanodots.

In order to effectively avoid the side effects induced by multiple components and tedious synthesis process, a simple therapy system based on one material to simultaneously realize both photothermal therapy (PTT) and photodynamic therapy (PDT) under single laser irradiation will promote the overall phototherapeutic efficiency and make the PTT/PDT system easier to operate. Here, by using transferrin (Tf) as protein template, ultrasmall CuS@transferrin nanodots (CuS@Tf NDs) were successfully synthesized through a facile one-pot protein-based biomineralization method. The obtained CuS@Tf NDs exhibited not only excellent photothermal conversion ability (34.4%) but also high photoactivated formation of reactive oxygen species (ROS) upon 980 nm near-infrared (NIR) irradiation. By loading the drug doxorubicin (DOX) to CuS@Tf NDs, a synergistic therapy system with multiple therapeutic effects combined PTT, PDT, chemotherapy (CT) and tumor targeting properties could be perfectly implemented together by CuS@Tf-DOX NDs without any complicated post-modification process. Results from the in vitro cell experiments confirmed that these CuS@Tf-DOX NDs could produce excellent effect on cancer cells with 88.5% cell inhibition rate. In comparison with the complicated systems based on "multiple-components-in-one" strategy, this therapy system based on one single material but possess multifunctional purpose is easy to operate and more suitable for clinical applications.

Selenium-Rich-Yeast Protects Against Aluminum-Induced Activating Nuclear Xenobiotic Receptors and Triggering Inflammation and Cytochromes P450 Systems in Mice Heart.

Aluminum (Al) poisoning is linked to the development of cardiovascular diseases, and dietary supplementation with selenium-rich-yeast (SeY) has been shown to prevent inflammatory conditions. We evaluated the preventive effect of SeY on Al-induced cardiotoxicity, and the possible underlying mechanisms. Mice were treated with SeY (0.1 mg/kg) and/or Al (10 mg/kg) by oral gavage for 4 weeks. Histopathological damage was observed in the heart of Al-treated mice, in addition to the transcriptional up/downregulation of nuclear xenobiotic receptors (NXRs), inflammatory cytokines and 15 CYP450s genes. SeY significantly inhibited these Al-induced histopathological and molecular changes, and restored these indicators to the control levels. These results suggest that SeY exerts a cardio-protective effect against Al-induced toxicity through the NXR system, inflammatory cytokines, and CYP450s genes.

Preliminary Study on the Effect of Bacillus amyloliquefaciens TL on Cecal Bacterial Community Structure of Broiler Chickens.

Probiotics can promote the health and growth performance of animals through modulation of intestinal microbiota. When used as a feed additive, they have the potential to minimize or abolish the use of antibiotics. In this study, we investigated the effect of the probiotic strain Bacillus amyloliquefaciens TL on the growth performance and cecum microflora composition in Cobb 500 broiler chickens. In total, 180 broilers were randomly divided into three groups-each group comprised 4 pens, and each pen contained 15 chickens. The three groups were fed either a control diet, or a diet supplemented with either the antibiotic chlortetracycline or B. amyloliquefaciens TL. Broilers were weighed, and cecum contents were collected on days 7, 14, 21, and 35, respectively. The broilers in both the antibiotic and probiotic groups exhibited significant weight gain compared with controls, exhibiting increases of 16.02% and 13.40%, respectively, after 35 days (P < 0.01). Similarly, the feed conversion ratio (FCR, 1-35 days) of broilers in the chlortetracycline and B. amyloliquefaciens TL groups was lower than that of the controls. HiSeq high-throughput sequencing of 16S rRNA of the cecal microbiota was performed on days 7, 14, 21, and 35, respectively. The Firmicutes/Bacteroidetes ratio was higher in the chlortetracycline and B. amyloliquefaciens TL groups than in the control group on days 14, 21, and 35, and especially on day 21. The prevalence of genera Oscillospira, Ruminococcus, Butyricicoccus, and Faecalibacterium (Firmicutes) was higher in the antibiotic and probiotic groups, while that of Bacteroides, Parabacteroides (Bacteroidetes), and Lactobacillus was higher in the control group. In this study, the changes in the microbiota of the probiotic group were similar to those in the antibiotic group. These results suggest that the probiotic strain B. amyloliquefaciens TL can modulate the cecal microbiota of broilers similar to chlortetracycline.

Abelmoschus manihot for Diabetic Nephropathy: A Systematic Review and Meta-Analysis.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Many trials have shown that Abelmoschus manihot could further improve proteinuria and protect kidney function in patients with DN when added to a renin-angiotensin system (RAS) blocker. A systematic assessment of the efficacy and safety of A. manihot in DN is essential. Eight electronic databases were searched to identify eligible trials published from inception to December 2017. The Cochrane Risk of Bias Tool was used to evaluate the methodological quality of eligible studies. Seventy-two studies with 5,895 participants were identified. The methodological quality of included studies was generally low. The results indicated that, compared to a RAS blocker, combined treatment of A. manihot with a RAS blocker was more effective for 24h urinary protein (24h UP) (mean difference [MD], -0.39 [95% confidence interval [CI], -0.46 to -0.33] g/d; P<0.00001), urinary albumin excretion rate (UAER)(MD, -19.90 [95% CI, -22.62 to -17.18] µg/min; P<0.00001), 24h UP reduction rate (risk ratio [RR], 1.43; 95% CI, 1.26-1.63; P<0.00001), normalization of UAER (RR, 1.48; 95% CI, 1.29-1.70; P<0.00001), and serum creatinine (SCr) (MD, -7.35 [95% CI, -9.95 to -4.76] umol/L; P<0.00001). None of these trials reported the ESRD rate. No statistically significant difference occurred between A. manihot combined with a RAS blocker and a RAS blocker alone in estimated glomerular filtration rate (eGFR) (MD, 4.43 [95% CI, -1.68 to 10.54] mL/min; P=0.16). A. manihot did not increase the rates of adverse drug events. A. manihot in addition to a RAS blocker was effective and safe to further improve proteinuria and protect kidney function in patients with DN. However, due to the generally low methodological quality, significant heterogeneity, and publication bias, high-quality randomized controlled trials are required to confirm these findings before the routine use of A. manihot can be recommended.

Phosphorus strategy in bloom-forming cyanobacteria (Dolichospermum and Microcystis) and its role in their succession.

Dolichospermum (formerly Anabaena) and Microcystis cause harmful cyanobacterial blooms in freshwater ecosystems worldwide. Input reduction of both nitrogen (N) and phosphorus (P) are commonly recognized as basic ways of controlling blooms, but little is known about the roles of nutrients and their using strategy among cyanobacteria in triggering the succession of diazotrophic to non-diazotrophic cyanobacteria. In this study, we investigated in situ responses of cyanobactria to ambient P status during the transition from Dolichospermum flos-aquae to Microcystis spp. in Lake Taihu and Lake Chaohu. While dominant in phytoplankton community, D. flos-aquae experienced P deficiency as evidenced by qualitative detection of extracellular phosphatase via enzyme labeled fluorescence (ELF). The percentage of ELF-labelled D. flos-aquae cells was 33% when it dominated the phytoplankton community, and was 78% when it co-dominated with Microcystis spp., indicating an increase in P deficiency. Meanwhile, no ELF-labelled Microcystis cells were observed while polyphosphate body (PPB) were present, suggesting that Microcystis spp. were not P deficient. Additionally, the percentages of Microcystis cells containing PPB showed an inverted "U-shaped" relationship with concentrations on soluble reactive phosphorus (SRP). To validate the field observation, a laboratory study of the monocultures of the dominant cyanobacteria was conducted. Extracellular alkaline phosphatase activity (APA) and PPB accumulation were regulated by P availability in monocultures of D. flos-aquae. Interestingly, no cell bound extracellular phosphatase was found on Microcystis aeruginasa even in the culture without P supply. Consistently, the expressions of phosphatase encoding gene phoX showed no differences among the treatments. The way in which PPB accumulation occurred in Microcystis spp. in response to P availability in the cultures was similar to that observed in the field, demonstrating a strategy of energy conservation over P accumulation. The competitive advantage of Microcystis spp. was displayed at low P concentrations: where it could rapidly uptake and store inorganic P, which also increased the P deficiency of the coexisting phytoplankton species. Responses of P-transport gene pstS confirmed this hypothesis. The physiological and molecular mechanisms mentioned above enable Microcystis to survive and proliferate in environment with low available P supply more efficiently. In conclusion, different cyanobacterial species have distinct ways of responding to P availability, suggesting that the control of cyanobacterial blooms by targeted nutrient reduction is largely dependent upon the dominant species. P reduction is more effective in controlling diazotrophic cyanobacteria than non-diazotrophic cyanobacteria.

Prevention of type 2 diabetes mellitus with acupuncture: Protocol for a systematic review and meta-analysis.

BACKGROUND: Prediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes mellitus (T2DM). Acupuncture has been increasingly used for prediabetes in China but its effect is unclear. We aim to assess the efficacy and safety of acupuncture in preventing or delaying incident diabetes among individuals with prediabetes. METHODS: The following 8 databases will be searched from inception to September 1, 2018: the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure database, Chinese Biomedical Literature database, Chinese Scientific Journal database, Wan Fang database, and Clinical Trials. The incidence of diabetes and regression toward normoglycemia will be accepted as the primary outcomes. The Cochrane Risk of Bias tool will be used to evaluate the methodologic quality of eligible studies. Meta-analysis will be performed by Review Manager 5.3. RESULTS: This study will provide a high-quality synthesis of current evidence of acupuncture in the prevention of T2DM from several aspects including the incidence of diabetes, regression toward normoglycemia, fasting plasma glucose, 2-hour plasma glucose level after a 75-g oral glucose tolerance test, glycosylated hemoglobin level, body mass index, and adverse drug events. CONCLUSIONS: The conclusion of this review will provide evidence to judge whether acupuncture is an effective and safe intervention for prediabetes. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018111236.

Removal of hERG potassium channel affinity through introduction of an oxygen atom: Molecular insights from structure-activity relationships of strychnine and its analogs.

Nux vomica has been effectively used in Traditional Chinese Medicine. The processing of Nux vomica is necessary to reduce toxicity before it can be used in clinical practice. However, the mechanism for processing detoxification is unclear. hERG channels have been subjected to a routine test for compound cardiac toxicity in the drug development process. Therefore, we examined the effects and mechanisms of strychnine and brucine, two main ingredients of Nux vomica, and their N-oxides on hERG channels. Strychnine and brucine exhibited concentration-dependent inhibition of hERG channels with IC50 values of 25.9 µM and 44.18 µM, respectively. However, their nitrogen oxidative derivatives produced by processing of Nux vomica, strychnine N-oxide and brucine N-oxide, lost their activity on hERG channels. Compared to their parent compounds, only an oxygen atom was introduced in the nitrogen oxidative isoforms to compensate for the N+ - charge, suggesting that the protonated nitrogen is the key group for strychnine and brucine binding to hERG channel. Alanine-mutagenesis identified Y652 is the most important residue for strychnine and brucine binding to hERG channel. Y652A mutation increased the IC50 for strychnine and brucine by 21.64-fold and 29.78-fold that of WT IhERG, respectively. Docking simulations suggested that the protonated nitrogen of strychnine and brucine formed a cation-π interaction with the aromatic ring of Y652. This study suggests that introduction of an oxygen to compensate for the N+ - charge could be a useful strategy for reducing hERG potency and increasing the safety margin of alkaloid-type compounds in drug development.

Selenium-Rich Yeast protects against aluminum-induced peroxidation of lipide and inflammation in mice liver.

To investigate the effect of Selenium Rich Yeast (SeY) on hepatotoxicity of Aluminium (Al), SeY (0.1 mg/kg) was orally administrated to aluminium-exposed mice (10 mg/kg) for 28 days. The risk of oxidative stress was assessed by detecting the total antioxidant capacity (T-AOC), catalase activity, H2O2 content, and mRNA levels of the Keap1/Nrf-2/HO-1 pathway. Inflammatory reactions were assessed by detecting the mRNA levels of inflammatory biomarkers. Our results showed that SeY protected against the liver histological changes induce by Al. The body weight gain of mice treated with SeY + Al restore to normal compare with mice exposed to Al alone. Al treatment significantly decreased the activities of antioxidant enzymes, reduced T-AOC levels, and up-regulated the mRNA level of Nrf2 and HO-1, thereby ultimately leading to peroxidation. SeY shown a significant protective effect against oxidative stress caused by Al. In addition, Al exposure induced inflammatory responses in rat liver by promoting the release of inflammatory cytokines (TNF-a, NF-kB, TNF-R1, IL-1, IL-6, and COX-2). SeY protected against changes in liver by regulating the mRNA expression levels of inflammatory factors. These results suggested that Se protected the liver from the Al-induced hepatotoxicity by regulating the mRNA level of Keap1/Nrf2/HO-1, and inhibited inflammatory responses by down-regulating the expression level of inflammatory cytokine.

High Selenium Yeast mitigates aluminum-induced cerebral inflammation by increasing oxidative stress and blocking NO production.

High Selenium Yeast (SeY) serves many important roles with respect to the maintenance of normal nervous system functioning. Studies have reported the nerve inflammation induced by Aluminum (Al) was associated with the increase of mortality. However, in-depth studies are required to verify the hypothesized neuro-protective efficacy of SeY against Al-induced cerebral damage through modulation of the inflammatory response. Here, mice were treated with SeY (0.1 mg/kg) and/or Al (10 mg/kg) by oral gavage for 28 days. Inflammation was assessed by histopathological examination and expression of biomarkers for inflammation. Furthermore, the oxidation-reduction levels and the NO production were assessed using diagnostic kits and RT-PCR. The data indicated that SeY significantly protected cerebrum against Al-induced pathological changes, in addition to the disordered expression of biomarkers of inflammation, the imbalance of oxidation-reduction, and the increase of NO production. Therefore, the chemoprotective potential of SeY against Al-induced cerebral inflammation via restore the levels of oxidation-reduction and the generation of NO was demonstrated.