Optimum Doses and Forms of Selenium Maintaining Reproductive Health via Regulating Homeostasis of Gut Microbiota and Testicular Redox, Inflammation, Cell Proliferation, and Apoptosis in Roosters.

BACKGROUND: There is a U-shaped relationship between dietary selenium (Se) ingestion and optimal sperm quality. OBJECTIVES: This study aimed to investigate the optimal dietary dose and forms of Se for sperm quality of breeder roosters and the relevant mechanisms. METHODS: In experiment 1, 18-wk-old Jingbai laying breeder roosters were fed a Se-deficient base diet (BD, 0.06 mg Se/kg), or the BD + 0.1, 0.2, 0.3, 0.4, 0.5, or 1.0 mg Se/kg for 9 wk. In experiment 2, the roosters were fed the BD or the BD + sodium selenite (SeNa), seleno-yeast (SeY), or Se-nanoparticles (SeNPs) at 0.2 mg Se/kg for 9 wk. RESULTS: In experiment 1, added dietary 0.2 and 0.3 mg Se/kg led to higher sperm motility and lower sperm mortality than the other groups at weeks 5, 7, and/or 9. Furthermore, added dietary 0.2-0.4 mg Se/kg produced better testicular histology and/or lower testicular 8-hydroxy-deoxyguanosine than the other groups. Moreover, integrated testicular transcriptomic and cecal microbiomic analysis revealed that inflammation, cell proliferation, and apoptosis-related genes and bacteria were dysregulated by Se deficiency or excess. In experiment 2, compared with SeNa, SeNPs slightly increased sperm motility throughout the experiment, whereas SeNPs slightly reduced sperm mortality compared with SeY at week 9. Both SeY and SeNPs decreased malondialdehyde in the serum than those of SeNa, and SeNPs led to higher glutathione peroxidase (GPX) and thioredoxin reductase activities and GPX1 and B-cell lymphoma 2 protein concentrations in the testis compared with SeY and SeNa. CONCLUSIONS: The optimal dietary Se dose for reproductive health of breeder roosters is 0.25-0.35 mg Se/kg, and SeNPs displayed better effects on reproductive health than SeNa and SeY in laying breeder roosters. The optimal doses and forms of Se maintain reproductive health of roosters associated with regulation intestinal microbiota homeostasis and/or testicular redox balance, inflammation, cell proliferation, and apoptosis.

Selenium-dependent glutathione peroxidase 1 regulates transcription of elongase 3 in murine tissues.

We have previously shown dysregulated lipid metabolism in tissues of glutathione peroxidase 1 (GPX1) overexpressing (OE) or deficient (KO) mice. This study explored underlying mechanisms of GPX1 in regulating tissue fatty acid (FA) biosynthesis. GPX1 OE, KO, and wild-type (WT) mice (n = 5, male, 3-6 months old) were fed a Se-adequate diet (0.3 mg/kg) and assayed for liver and adipose tissue FA profiles and mRNA levels of key enzymes of FA biosynthesis and redox-responsive transcriptional factors (TFs). These three genotypes of mice (n = 5) were injected intraperitoneally with diquat, ebselen, and N-acetylcysteine (NAC) at 10, 50, and 50 mg/kg of body weight, respectively, and killed at 0 and 12 h after the injections to detect mRNA levels of FA elongases and desaturases and the TFs in the liver and adipose tissue. A luciferase reporter assay with targeted deletions of mouse Elovl3 promoter was performed to determine transcriptional regulations of the gene by GPX1 mimic ebselen in HEK293T cells. Compared with WT, GPX1 OE and KO mice had 9-42% lower (p < 0.05) and 36-161% higher (p < 0.05) concentrations of C20:0, C22:0, and C24:0 in these two tissues, respectively, along with reciprocal increases and decreases (p < 0.05) of Elovl3 transcripts. Ebselen and NAC decreased (p < 0.05), whereas diquat decreased (p < 0.05), Elovl3 transcripts in the two tissues. Overexpression and knockout of GPX1 decreased (p < 0.05) and increased (p < 0.05) ELOVL3 levels in the two tissues, respectively. Three TFs (GABP, SP1, and DBP) were identified to bind the Elovl3 promoter (-1164/+33 base pairs). Deletion of DBP (-98/-86 base pairs) binding domain in the promoter attenuated (13%, p < 0.05) inhibition of ebselen on Elovl3 promoter activation. In summary, GPX1 overexpression down-regulated very long-chain FA biosynthesis via transcriptional inhibition of the Elovl3 promoter activation.

Alleviation of Alcoholic Fatty Liver by Dendrobium officinale Flower Extracts due to Regulation of Gut Microbiota and Short-Chain Fatty Acids in Mice Exposed to Chronic Alcohol.

Alcoholic fatty liver disease (AFLD) is caused by long-term heavy alcohol consumption; therefore, useful and practical methods for the prevention of AFLD are urgently needed. The edible flower of Dendrobium officinale contains diverse flavonoids, and has shown antioxidant activity as well as antihypertensive and anti-inflammatory effects. In this study, an AFLD model was established, the protective effect of D. officinale flower (DOF) ethanol extract on AFLD was evaluated, and its mechanisms were investigated by analyzing gut microbiota and short-chain fatty acids (SCFAs). DOF extract (DOFE) supplementation promoted alcohol metabolism, restored hepatic antioxidant capacity, alleviated oxidative stress, reduced inflammatory factor levels, and inhibited dyslipidemia induced by alcohol intake in chronic alcohol-exposed mice, especially in the high DOFE group. Moreover, DOFE supplementation increased the diversity, structure, and composition of the gut microbiota in mice, restored some of the abnormal SCFA levels caused by AFLD, and helped restore intestinal function. DOFE supplementation significantly increased the relative abundance of Akkermansia, suggesting that Akkermansia may be a potential target of the protective effect of DOFE. Therefore, DOFE supplementation to improve the composition of the gut microbiota may be an effective therapeutic strategy for the prevention of AFLD.

Supranutrition of microalgal docosahexaenoic acid and calcidiol improved growth performance, tissue lipid profiles, and tibia characteristics of broiler chickens.

BACKGROUND: Docosahexaenoic acid (DHA) and calcidiol could be enriched in chicken for improving public nutrition and health. It remains unclear if supranutritional levels of DHA and calcidiol impair growth performance or metabolism of broiler chickens. This study was to determine singular and combined effects of high levels of supplemental DHA-rich microalgal biomass or oil and calcidiol on growth performance, concentrations of triglycerides, cholesterol, and nonesterfied fatty acids in plasma, liver, breast, and thigh, and biophysical properties of tibia. METHODS: In Exp. 1, 144 day-old Cornish chicks were divided into 4 groups (6 cages/treatment, 6 birds/cage), and were fed a corn-soybean meal basal diet (BD), BD + 10,000 IU calcidiol/kg (BD + Cal), BD + 1% DHA-rich Aurantiochytrium (1.2 g DHA/kg; BD + DHA), and BD + Cal + DHA for 6 weeks. In Exp. 2, 180 day-old chicks were divided into 5 groups, and were fed: BD, BD + DHA (0.33% to 0.66% oil, 1.5 to 3.0 g DHA/kg), BD + DHA + EPA (1.9% to 3.8% eicosapentaenoic acid-rich Nannochloropsis sp. CO18, 0.3 to 0.6 g EPA/kg), BD + DHA + calcidiol (6000 to 12,000 IU/kg diet), and BD + DHA + EPA + Cal for 6 weeks. RESULTS: Birds fed BD + Cal diet in Exp. 1 and BD + DHA + EPA diet in Exp. 2 had higher (P < 0.05) body weight gain (10%-11%) and gain:feed ratio (7%), and lower (P < 0.05) total cholesterol and triglyceride concentrations in plasma (18%-54%), liver (8%-26%), breast (19%-26%), and thigh (10%-19%), respectively, over the controls. The two diets also improved (P < 0.05) tibial breaking strength (8%-24%), total bone volume (2%-13%), and (or) bone mineral density (3%-19%) of chickens. CONCLUSION: Supranutrition of dietary calcidiol and DHA alone or together did not produce adverse effects, but led to moderate improvements of growth performance, lipid profiles of plasma and muscle, and bone properties of broiler chickens.

Both selenium deficiency and excess impair male reproductive system via inducing oxidative stress-activated PI3K/AKT-mediated apoptosis and cell proliferation signaling in testis of mice.

Selenium (Se) deficiency or excess impairs testicular development and spermatogenesis, while the underlying mechanisms in this regard remain unclear. This study was designed to explore the molecular biology of Se deficiency or excess in spermatogenesis in mice. Three-week-old male mice (n = 10 mice/diet) were fed with Se-deficient diet (SeD, 0.02 mg Se/kg), adequate-Se diet (SeA, 0.2 mg Se/kg), or excess-Se diet (SeE, 2.0 mg Se/kg) for 5 months. Compared with SeA, SeD reduced (P < 0.05) the body weight (10.4%) and sperm density (84.3%) but increased (P < 0.05) sperm deformity (32.8%); SeE decreased (P < 0.05) the sperm density (78.5%) and sperm motility (35.9%) of the mice. Meanwhile, both SeD and SeE increased (P < 0.05) serum FSH concentrations (10.4-25.6%) and induced testicular damage in mice in comparison with the SeA. Compared with SeA, SeD increased (P < 0.05) the 8-OHdG concentration by 25.5%; SeE increased (P < 0.05) both MDA and 8-OHdG concentrations by 118.8-180.3% in testis. Furthermore, transcriptome analysis showed that there 1325 and 858 transcripts were altered (P < 0.05) in the testis by SeD and SeE, respectively, compared with SeA. KEGG pathway analysis revealed that these differentially expressed genes were mainly enriched in the PI3K-AKT signaling pathway, which is regulated by oxidative stress. Moreover, western blotting analysis revealed that SeD and SeE dysregulated PI3K-AKT-mediated apoptosis and cell proliferation signaling, including upregulating (P < 0.05) caspase 3, cleaved-caspase 3, BCL-2 and (or) P53 and downregulating (P < 0.05) PI3K, p-AKT, p-mTOR, 4E-BP1, p-4E-BP1 and (or) p-p70S6K in the testis of mice compared with SeA. Additionally, compared with SeA, both SeD and SeE increased (P < 0.05) GPX3 and SELENOO; SeD decreased (P < 0.05) GPX1, TXRND3 and SELENOW, but SeE increased (P < 0.05) production of three selenoproteins in the testis. Conclusively, both Se deficiency and excess impairs male reproductive system in mice, potentially with the induction of oxidative stress and activation of PI3K/AKT-mediated apoptosis and cell proliferation signaling in the testis.

Evidence and Metabolic Implications for a New Non-Canonical Role of Cu-Zn Superoxide Dismutase.

Copper-zinc superoxide dismutase 1 (SOD1) has long been recognized as a major redox enzyme in scavenging superoxide radicals. However, there is little information on its non-canonical role and metabolic implications. Using a protein complementation assay (PCA) and pull-down assay, we revealed novel protein-protein interactions (PPIs) between SOD1 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) or epsilon (YWHAE) in this research. Through site-directed mutagenesis of SOD1, we studied the binding conditions of the two PPIs. Forming the SOD1 and YWHAE or YWHAZ protein complex enhanced enzyme activity of purified SOD1 in vitro by 40% (p < 0.05) and protein stability of over-expressed intracellular YWHAE (18%, p < 0.01) and YWHAZ (14%, p < 0.05). Functionally, these PPIs were associated with lipolysis, cell growth, and cell survival in HEK293T or HepG2 cells. In conclusion, our findings reveal two new PPIs between SOD1 and YWHAE or YWHAZ and their structural dependences, responses to redox status, mutual impacts on the enzyme function and protein degradation, and metabolic implications. Overall, our finding revealed a new unorthodox role of SOD1 and will provide novel perspectives and insights for diagnosing and treating diseases related to the protein.

Pentacyclic triterpenoids from spikes of Prunella vulgaris L. with thyroid tumour cell cytostatic bioactivities.

Five new triterpenoids, including four ursane types (1-4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6-20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1-20). The results indicated that (7-9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73-71.41 µM (cisplatin as positive control, IC50 14.49 ± 0.97 µM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.

The immuneoreaction and antioxidant status of Chinese mitten crab (Eriocheir sinensis) involve protein metabolism and the response of mTOR signaling pathway to dietary methionine levels.

To study the effects of dietary methionine on growth performance, immunity, antioxidant capacity, protein metabolism, inflammatory response and apoptosis factors in Chinese mitten crabs (Eriocheir sinensis). Five diets with different methionine levels (0.63%, 0.85%, 1.06%, 1.25% and 1.47%) were fed to E. sinensis for 8 weeks. Results showed that in the 1.25% Met group, both growth performance and feed utilization were significantly increased. The crude protein content of crab muscle in the 1.06% and 1.25% Met groups was significantly higher than that in the control group. The immune and antioxidant enzyme activities, as well as gene expression levels of anti-lipopolysaccharide factor 1 (ALF1), Crustin-1, prophenoloxidase (proPO), cap 'n' collar isoform C (CncC) in 1.25% Met group were significantly higher than other groups. The activities of adenosine deaminase (ADA) and glutamate transaminase (GPT) in serum decreased first and then increased with the increase of methionine content, while the changes of ADA and GPT in hepatopancreas increased first and then decreased. 1.25% Met group exhibited significantly increased levels of GOT, GPT, and ADA compared to the control group. 1.25% Met diet group significantly up-regulated protein synthesis and anti-apoptotic factors, and significantly down-regulated inflammatory and pro-apoptotic factors in hepatopancreas. At 1.25% in the diet, methionine was found to boost E. sinensis growth, muscle protein deposition and immunity, as well as its antioxidant capacity. Combined with the above results, based on the expression of factors involved in the mammalian target of rapamycin (mTOR) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway, it is proved that methionine can not only promote protein metabolism, improve feed utilization, but also alleviate the inflammatory response and apoptosis caused by oxidative stress in the body.

Selenium-Enriched Cardamine violifolia Increases Selenium and Decreases Cholesterol Concentrations in Liver and Pectoral Muscle of Broilers.

BACKGROUND: Supernutrition of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains >80% of Se in organic forms. OBJECTIVES: This study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism. METHODS: Day-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage) and were fed either a corn-soy base diet (BD, 0.13-0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.20-0.21mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism-related genes were determined in the pectoral muscle and liver. RESULTS: The 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4-127% and decreased (P < 0.05) total cholesterol concentrations by 12.5-46.7% and/or triglyceride concentrations by 28.8-31.1% in the pectoral muscle and/or liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (sterol regulatory element binding transcription factor 2 and diacylglycerol O-acyltransferase 2) and upregulated (P < 0.05) hydrolysis and ß-oxidation of fatty acid-related proteins (lipoprotein lipase, fatty acid binding protein 1, and carnitine palmitoyltransferase 1A), as well as selenoprotein P1 and thioredoxin reductase activity in the pectoral muscle and/or liver compared with SeNa. CONCLUSIONS: Compared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.

Schisandraceae triterpenoids: A review of phytochemistry, bioactivities and synthesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Schisandraceae family have a rich and medicinal history dating back to ancient times. Many of them are used as folk medicine in the treatment of chronic coughs, asthma, nocturnal emission, spontaneous sweating, night sweats, palpitation, insomnia and thirst. AIM OF THE REVIEW: The current review is carried out on triterpenoids from the Schisandraceae family, aiming to comprehensively summarize their phytochemistry, pharmacology and synthesis and provide new insights to the chemical and pharmacological study and rational utilization on medicinal plants of the Schisandarceae family. MATERIALS AND METHODS: The information was searched from the scientific literature published from June 2014 to November 2021 on the online databases (including PubMed, CNKI, Elsevier, SciFinder and Web of Science) and other bibliography (e.g. the Chinese Pharmacopoeia, 2020 edition, Chinese herbal books). The scientific literature related to phytochemistry, pharmacology, biological activites and synthesis of triterpenoids from the Schisandraceae family was gathered. RESULTS: From June 2014 to November 2021, there were approximately 211 novel triterpenoids isolated and identified from 18 species of the Schisandraceae family. These compounds exhibit tremendous diversity in their structures, and some of them possess promising pharmacological activities, including anti-viral, anti-tumor, anti-inflammatory, hepatoprotective, immunosuppressive activities and neuroprotective effects. In the attempt to synthesize active compounds, the total synthesis of 13 schinortriterpenoids belonging to five structural types was successfully completed. CONCLUSIONS: Studies of triterpenoids from the Schisandraceae family are well documented in this review (from June 2014 to November 2021), and it is also well acknowledged that they are valuable resources with medicinal efficacy. However, relevant pharmacological studies are limited to in vitro tests, and data from in vivo studies and toxicology are lacking or unavailable. Fortunately, there is growing interest in the synthesis of active compounds, which should serve as an approach for accessing active compounds to develop in vivo or toxicity studies, with a view of clarifying their in vitro and vivo mechanisms for more effective and safe natural drugs.

Dietary Selenium Across Species.

This review traces the discoveries that led to the recognition of selenium (Se) as an essential nutrient and discusses Se-responsive diseases in animals and humans in the context of current understanding of the molecular mechanisms of their pathogeneses. The article includes a comprehensive analysis of dietary sources, nutritional utilization, metabolic functions, and dietary requirements of Se across various species. We also compare the function and regulation of selenogenomes and selenoproteomes among rodents, food animals, and humans. The review addresses the metabolic impacts of high dietary Se intakes in different species and recent revelations of Se metabolites, means of increasing Se status, and the recycling of Se in food systems and ecosystems. Finally, research needs are identified for supporting basic science and practical applications of dietary Se in food, nutrition, and health across species.

Novel zinc sources as antimicrobial growth promoters for monogastric animals: a review.

The essentiality of zinc for animals has been recognized over 80 years. Zinc is an essential trace element that is a component of many enzymes and is associated with the various hormones. Apart from the nutritional function, zinc has antimicrobial property and often be supplemented in diets in the quantities greater than which is required to meet the nutritional requirement, especially for weaning pigs. This review will focus on the application of pharmacological zinc and its mechanisms which may be responsible for the effects of zinc on performance and health of monogastric animals. Various novel sources of zinc in non-ruminant animal production will also be discussed. These should assist in more precisely formulating feed to maximize the production performance and to maintain the health condition of monogastric animals.

Rational Design Strategy of Novel Energy Storage Systems: Toward High-Performance Rechargeable Magnesium Batteries.

Rechargeable magnesium batteries (RMBs) are promising candidates to replace currently commercialized lithium-ion batteries (LIBs) in large-scale energy storage applications owing to their merits of abundant resources, low cost, high theoretical volumetric capacity, etc. However, the development of RMBs is still facing great challenges including the incompatibility of the electrolyte and the lack of suitable cathode materials with high reversible capacity and fast kinetics of Mg2+ . While tremendous efforts have been made to explore compatible electrolytes and appropriate electrode materials, the rational design of unconventional Mg-based battery systems is another effective strategy for achieving high electrochemical performance. This review specifically discusses the recent research progress of various Mg-based battery systems. First, the optimization of electrolyte and electrode materials for conventional RMBs is briefly discussed. Furthermore, various Mg-based battery systems, including Mg-chalcogen (S, Se, Te) batteries, Mg-halogen (Br2 , I2 ) batteries, hybrid-ion batteries, and Mg-based dual-ion batteries are systematically summarized. This review aims to provide a comprehensive understanding of different Mg-based battery systems, which can inspire latecomers to explore new strategies for the development of high-performance and practically available RMBs.

Three new pyrrole alkaloids from the endophytic fungus Albifimbria viridis.

Three new pyrrole alkaloids albifipyrrols A-C (1-3), were isolated from the endophytic fungus Albifimbria viridis collected from the Chinese medicinal plant. Their structures were elucidated by extensive NMR and HRESIMS spectrometric analyses. All compounds were evaluated for immunosuppressive activity. Fortunately, compound 2 exhibits certain inhibition specifically against the LPS-induced proliferation of B lymphocyte cells with IC50 value 16.16 µM.

Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Gut Microbiota as a Mediator of Essential and Toxic Effects of Zinc in the Intestines and Other Tissues.

The objective of the present study was to review the existing data on the association between Zn status and characteristics of gut microbiota in various organisms and the potential role of Zn-induced microbiota in modulating systemic effects. The existing data demonstrate a tight relationship between Zn metabolism and gut microbiota as demonstrated in Zn deficiency, supplementation, and toxicity studies. Generally, Zn was found to be a significant factor for gut bacteria biodiversity. The effects of physiological and nutritional Zn doses also result in improved gut wall integrity, thus contributing to reduced translocation of bacteria and gut microbiome metabolites into the systemic circulation. In contrast, Zn overexposure induced substantial alterations in gut microbiota. In parallel with intestinal effects, systemic effects of Zn-induced gut microbiota modulation may include systemic inflammation and acute pancreatitis, autism spectrum disorder and attention deficit hyperactivity disorder, as well as fetal alcohol syndrome and obesity. In view of both Zn and gut microbiota, as well as their interaction in the regulation of the physiological functions of the host organism, addressing these targets through the use of Zn-enriched probiotics may be considered an effective strategy for health management.

Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway.

BACKGROUND: Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used to improve cognitive impairment. However, the underlying neuroprotective mechanism of HPTQ treated for diabetic cognitive dysfunction (DCD) remains unclear. The purpose of this study was to investigate the neuroprotective mechanism of HPTQ in DCD mice based on molecular docking. METHODS: To investigate the neuroprotective effect of HPTQ in DCD, the Morris water maze (MWM), novel object recognition (NOR) test was used to detect the learning and memory changes of mice; hematoxylin-eosin (HE) staining was used to investigate the damage of hippocampal neurons; the western blot (WB) was used to examine the level of brain-derived neurotrophic factor (BDNF) of hippocampus. To investigate the neuroprotective mechanism of HPTQ in DCD, molecular docking was used to predict the possible target proteins of different active components in HPTQ and then the WB was used to verify the expression of key target proteins in the hippocampus of mice. RESULTS: HPTQ improved the learning and memory ability, hippocampal neuron damage, and the level of BDNF in the hippocampus of the DCD model treated with HFD/STZ for 12 weeks. Besides, the results of molecular docking showed that the main chemical components of HPTQ could be well combined with the targets of Bcl-2-associated X (Bax) and B-cell lymphoma2 (Bcl-2) and caspase-3. The levels of Bax/Bcl-2 protein ratio and caspase-3 increased in the DCD model while the HPTQ inhibited it. In addition, HPTQ restored DCD-induced decline of p-CREB, BDNF, TrkB, and p-Akt in the hippocampus. CONCLUSIONS: These data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway.

Replacing fish oil and astaxanthin by microalgal sources produced different metabolic responses in juvenile rainbow trout fed 2 types of practical diets.

Dietary fish oil supplementation provides n-3 long-chained polyunsaturated fatty acids for supporting fish growth and metabolism and enriching fillet with eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; c22:6n-3). Two experiments were performed as a 3 × 2 factorial arrangement of dietary treatments for 16 wk to determine effects and mechanisms of replacing 0%, 50%, and 100% fish oil with DHA-rich microalgae in combination with synthetic vs. microalgal source of astaxanthin in plant protein meal (PM)- or fishmeal (FM)- based diets for juvenile rainbow trout (Oncorhynchus mykiss). Fish (22 ± 0.26 g) were stocked at 17/tank and 3 tanks/diet. The 100% fish oil replacement impaired (P < 0.0001) growth performance, dietary protein and energy utilization, body indices, and tissue accumulation of DHA and EPA in both diet series. The impairments were associated (P < 0.05) with upregulation of hepatic gene expression related to growth (ghr1and igf1) and biosynthesis of DHA and EPA (fads6 and evol5) that was more dramatic in the FM than PM diet-fed fish, and more pronounced on tissue EPA than DHA concentrations. The source of astaxanthin exerted interaction effects with the fish oil replacement on several measures including muscle total cholesterol concentrations. In conclusion, replacing fish oil by the DHA-rich microalgae produced more negative metabolic responses than the substitution of synthetic astaxanthin by the microalgal source in juvenile rainbow trout fed 2 types of practical diets.

The vascular endothelial growth factor trap aflibercept induces vascular dysfunction and hypertension via attenuation of eNOS/NO signaling in mice.

Aflibercept, as a soluble decoy vascular endothelial growth factor receptor, Which has been used as a first-line monotherapy for cancers. Aflibercept often causes cardiovascular toxicities including hypertension, but the mechanisms underlying aflibercept-induced hypertension remain unknown. In this study we investigated the effect of short-term and long-term administration of aflibercept on blood pressure (BP), vascular function, NO bioavailability, oxidative stress and endothelin 1 (ET-1) in mice and cultured endothelial cells. We showed that injection of a single-dose of aflibercept (18.2, 36.4 mg/kg, iv) rapidly and dose-dependently elevated BP in mice. Aflibercept treatment markedly impaired endothelial-dependent relaxation (EDR) and resulted in NADPH oxidases 1 (NOX1)- and NADPH oxidases 4 (NOX4)-mediated generation of ROS, decreased the activation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) concurrently with a reduction in nitric oxide (NO) production and elevation of ET-1 levels in mouse aortas; these effects were greatly attenuated by supplementation of L-arginine (L-arg, 0.5 or 1.0 g/kg, bid, ig) before aflibercept injection. Similar results were observed in L-arg-pretreated cultured endothelial cells, showing markedly decreased ROS accumulation and AKT/eNOS/NO signaling impairment induced by aflibercept. In order to assess the effects of long-term aflibercept on hypertension and to evaluate the beneficial effects of L-arg supplementation, we administered these two drugs to WT mice for up to 14 days (at an interval of two days). Long-term administration of aflibercept resulted in a sustained increase in BP and a severely impaired EDR, which are associated with NOX1/NOX4-mediated production of ROS, increase in ET-1, inhibition of AKT/eNOS/NO signaling and a decreased expression of cationic amino acid transporter (CAT-1). The effects caused by long-term administration were greatly attenuated by L-arg supplementation in a dose-dependent manner. We conclude that aflibercept leads to vascular dysfunction and hypertension by inhibiting CAT-1/AKT/eNOS/NO signaling, increasing ET-1, and activating NOX1/NOX4-mediated oxidative stress, which can be suppressed by supplementation of L-arg. Therefore, L-arg could be a potential therapeutic agent for aflibercept-induced hypertension.

Glutathione peroxidase-1 and neuromodulation: Novel potentials of an old enzyme.

Glutathione peroxidase (GPx) acts in co-ordination with other signaling molecules to exert its own antioxidant role. We have demonstrated the protective effects of GPx,/GPx-1, a selenium-dependent enzyme, on various neurodegenerative disorders (i.e., Parkinson's disease, Alzheimer's disease, cerebral ischemia, and convulsive disorders). In addition, we summarized the recent findings indicating that GPx-1 might play a role as a neuromodulator in neuropsychiatric conditions, such as, stress, bipolar disorder, schizophrenia, and drug intoxication. In this review, we attempted to highlight the mechanistic scenarios mediated by the GPx/GPx-1 gene in impacting these neurodegenerative and neuropsychiatric disorders, and hope to provide new insights on the therapeutic interventions against these disorders.