Selenium maintains intestinal epithelial cells to activate M2 macrophages against deoxynivalenol injury.

Selenium (Se) is indispensable in alleviating various types of intestinal injuries. Here, we thoroughly investigated the protective effect of Se on the regulation of the epithelial cell-M2 macrophages pathway in deoxynivalenol (DON)-induced intestinal damage. In the present study, Se has positive impacts on gut health by improving gut barrier function and reducing the levels of serum DON in vivo. Furthermore, our study revealed that Se supplementation increased the abundances of GPX4, p-PI3K, and AKT, decreased the levels of 4-HNE and inhibited ferroptosis. Moreover, when mice were treated with DON and Fer-1(ferroptosis inhibitor), ferroptosis was suppressed and PI3K/AKT pathway was activated. These results indicated that GPX4-PI3K/AKT-ferroptosis was a predominant pathway in DON-induced intestinal inflammation. Interestingly, we discovered that both the number of M2 anti-inflammatory macrophages and the levels of CSF-1 decreased while the pro-inflammatory cytokine IL-6 increased in the intestine and MODE-K cells supernatant. Therefore, Se supplementation activated the CSF-1-M2 macrophages axis, resulting in a decrease in IL-6 expression and an enhancement of the intestinal anti-inflammatory capacity. This study provides novel insights into how intestinal epithelial cells regulate the CSF-1-M2 macrophage pathway, which is essential in maintaining intestinal homeostasis confer to environmental hazardous stimuli.

Identification of Characteristic Bioactive Compounds in Silkie Chickens, Their Effects on Meat Quality, and Their Gene Regulatory Network.

Silkie chicken, an important chicken breed with high medicinal and nutritional value, has a long history of being used as a dietary supplement in China. However, the compounds with health-promoting effects in Silkie chickens remain unclear. In the present study, we conducted a comprehensive analysis of metabolic and lipidomic profiles to identify the characteristic bioactive compounds in Silkie chickens, using a common chicken breed as control. The results showed that the levels of 13 metabolites including estradiol, four lipid subclasses including cardiolipin (CL), eight lipid molecules, and three fatty acids including docosahexaenoic acid (C22:6) were significantly increased in Silkie chickens, which have physiological activities such as resisting chronic diseases and improving cognition. These characteristic bioactive compounds have effects on meat quality characteristics, including improving its water-holding capacity and umami taste and increasing the content of aromatic compounds and phenols. The differentially expressed genes (DEGs) between the two chicken breeds revealed the regulatory network for these characteristic bioactive compounds. Fifteen DEGs, including HSD17B1, are involved in the synthesis of characteristic metabolites. Eleven DEGs, including ELOVL2, were involved in the synthesis and transport of characteristic lipids and fatty acids. In summary, we identified characteristic bioactive compounds in Silkie chickens, and analyzed their effects on meat quality characteristics. This study provided important insight into Silkie chicken meat as a functional food.

Inhibition of the thioredoxin system for radiosensitization therapy of cancer.

Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including gold nanoparticles (GNPs), gold triethylphosphine cyanide ([Au(SCN) (PEt3)]), auranofin, ceria nanoparticles (CONPs), curcumin and its derivatives, piperlongamide, indolequinone derivatives, micheliolide, motexafin gadolinium, and ethane selenide selenidazole derivatives (SeDs), are meticulously elucidated in terms of their applications in radiotherapy. In this review, the sensitization mechanisms and the current research progress of these radiosensitizers are discussed in detail, with the overall aim of providing valuable insights for the judicious application of Trx system inhibitors in the field of cancer radiosensitization therapy.

Enrichment efficiency of lutein in eggs and its function in improving fatty liver hemorrhagic syndrome in aged laying hens.

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.

Deposition and bioconversion law of ß-carotene in laying hens after long-term supplementation under adequate vitamin A status in the diet.

ß-Carotene, because it is the precursor of vitamin A and has versatile biological roles, has been applied as a feed additive in the poultry industry for a long time. In this study, we investigated the deposition and bioconversion of ß-carotene in laying hens. A total of 600 Hy-line brown laying hens at 40 wk of age were randomly divided into 5 dietary treatments, each group's dietary supplemental levels of ß-carotene were 0, 15, 30, 60, 120 mg/kg feed, and the vitamin A levels were all 8,000 IU/kg. After 14-wk trial, samples were collected, then carotenoids and different forms of vitamin A were detected using the novel method developed by our laboratory. We found that dietary ß-carotene treatment had no significant effects on laying hens' production performance and egg quality (P > 0.05), except the yolk color. The deposition of ß-carotene in the body gradually increased (P < 0.01) with the supplemental dose, whereas the contents of lutein and zeaxanthin decreased (P < 0.05). When the ß-carotene supplemental level was above 30 mg/kg in the diet, the different forms of vitamin A in in serum, liver, ovary, and yolks were increased compared to the control group (P < 0.05). However, these indicators decreased when the additional dose was 120 mg/kg. Moreover, the mRNA levels of the genes involved in ß-carotene absorption, bioconversion, and negative feedback regulation in duodenal mucosa and liver were upregulated after long-term feeding (P < 0.05). Histological staining of the ovaries indicated that the deposition of ß-carotene led to a lower rate of follicle atresia (P < 0.05), and this positive effects may be related to the antioxidant function of ß-carotene, which caused a reduction of oxidation products in the ovary (P < 0.05). Altogether, ß-carotene could accumulate in laying hens intactly and exert its biological functions in tissue. Meanwhile, a part of ß-carotene could also be converted into vitamin A but this bioconversion has an upper limit and negative feedback regulation.

The Effect of Epimedium Isopentenyl Flavonoids on the Broiler Gut Health Using Microbiomic and Metabolomic Analyses.

Epimedium (EM), also known as barrenwort, is a traditional medicinal plant rich in isopentenyl flavonols, which have beneficial biological activities and can improve human and animal health, but its mechanism is still unclear. In this study, ultra-high-performance liquid chromatography/quadrupole-time-of-flight-mass spectrometry (UHPLC-Q-TOF/MS) and ultra-high-performance liquid chromatography triple-quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) were used to analyse the main components of EM, and isopentenyl flavonols such as Epimedin A, B, and C as well as Icariin were the major components of EM. Meanwhile, broilers were selected as model animals to illuminate the mechanism of Epimedium isopentenyl flavonols (EMIE) on gut health. The results showed that supplementation with 200 mg/kg EM improved the immune response, increased cecum short-chain fatty acids (SCFAs) and lactate concentrations, and improved nutrient digestibility in broilers. In addition, 16S rRNA sequencing showed that EMIE altered the composition of cecal microbiome, increasing the relative abundance of beneficial bacteria (Candidatus Soleaferrea and Lachbospiraceae NC2004 group and Butyricioccus) and reducing that of harmful bacteria (UBA1819, Negativibacillus, and Eisenbergiella). Metabolomic analysis identified 48 differential metabolites, of which Erosnin and Tyrosyl-Tryptophan were identified as core biomarkers. Erosnin and tyrosyl-tryptophan are potential biomarkers to evaluate the effects of EMIE. This shows that EMIE may regulate the cecum microbiota through Butyricicoccus, with changes in the relative abundance of the genera Eisenbergiella and Un. Peptostreptococcaceae affecting the serum metabolite levels of the host. EMIE is an excellent health product, and dietary isopentenyl flavonols, as bioactive components, can improve health by altering the microbiota structure and the plasma metabolite profiles. This study provides the scientific basis for the future application of EM in diets.

Pharmacokinetics, absorption and transport mechanism for ginseng polysaccharides.

BACKGROUND: Ginseng polysaccharide (GP) is one of the most abundant components in Panax ginseng. However, the absorption pathways and mechanisms of GPs have not been investigated systematically due to the challenges of their detection. METHODS: The fluorescein isothiocyanate derivative (FITC) was employed to label GP and ginseng acidic polysaccharide (GAP) to obtain target samples. HPLC-MS/MS assay was used to determine the pharmacokinetics of GP and GAP in rats. The Caco-2 cell model was used to investigate the uptake and transport mechanisms of GP and GAP in rats. RESULTS: Our results demonstrated that the absorption of GAP was more than that of GP in rats after gavage administration, while there was no significant difference between both after intravenous administration. In addition, we found that GAP and GP were more distributed in the kidney, liver and genitalia, suggesting that GAP and GP are highly targeted to the liver, kidney and genitalia. Importantly, we explored the uptake mechanism of GAP and GP. GAP and GP are endocytosed into the cell via lattice proteins or niche proteins. Both are transported lysosomally mediated to the endoplasmic reticulum (ER) and then enter the nucleus through the ER, thus completing the process of intracellular uptake and transportation. CONCLUSION: Our results confirm that the uptake of GPs by small intestinal epithelial cells is primarily mediated via lattice proteins and the cytosolic cellar. The discovery of important pharmacokinetic properties and the uncovering of the absorption mechanism provide a research rationale for the research of GP formulation and clinical promotion.

Development and application of a SFC-DAD-MS/MS method to determine carotenoids and vitamin A in egg yolks from laying hens supplemented with ß-carotene.

ß-Carotene, a provitamin A carotenoid, can be converted into vitamin A in animals' bodies, and can also be accumulated intactly in many animal products. In this study, supercritical fluid chromatography-tandem mass spectrometry was utilized to determine ß-carotene and different forms of vitamin A in eggs simultaneously. According to the results, ß-carotene contained in yolk reached a plateau after about 2 weeks of supplementation. With an increase in dietary supplement level, the amount of ß-carotene gradually increased, as well as slightly changing the yolk color. Moreover, the contents of retinoids including retinol, retinyl propionate, retinyl palmitate and retinyl stearate were also elevated in yolks with the ß-carotene additive levels; meanwhile, the lutein and zeaxanthin decreased. On the whole, ß-carotene in the diet of laying hens could be partially deposited in egg yolk, and the contents of vitamin A in yolk could be increased due to ß-carotene bioconversion.

Dietary supplementation with astaxanthin alleviates ovarian aging in aged laying hens by enhancing antioxidant capacity and increasing reproductive hormones.

We investigated the effects of astaxanthin supplementation on the egg quality, antioxidant capacity, and ovarian aging of aged laying hens. Six groups of 68-wk-old Hy-line brown laying hens with six replications each, fifteen chickens in each replicate were fed for 12 wk. The control group was fed a basal diet, the positive control group was fed the basal diet supplemented with 100 mg/kg vitamin E, and the experimental groups were fed the basal diet supplemented with 15 mg/kg, 30 mg/kg, 45 mg/kg, or 60 mg/kg astaxanthin (Ax15, Ax30, Ax45, and Ax60, respectively). The results showed that astaxanthin accumulated in the egg yolks and improved egg yolk color (P < 0.01) and Haugh unit (P < 0.05). Compared with the control group, the experimental groups a higher number of follicles in the ovary and a lower rate of atresia (P < 0.01). Astaxanthin increased the expression of nuclear factor e2-related factor 2 (NRF2) in the ovary (P < 0.05), enhanced the antioxidant capacity of aged laying hens (P < 0.05), and reduced cellular apoptosis (P < 0.05). In addition, astaxanthin improved serum reproductive hormone levels (follicle-stimulating hormone, luteinizing hormone, and progesterone) (P < 0.05) with a maximum value observed in Ax60. However, astaxanthin had no effects on estrogen level (P > 0.05). The expression of FSHR and CYP11A1 increased in the follicular granulosa cells (P < 0.05). Therefore, astaxanthin prevented ovarian aging by improving the antioxidant capacity of laying hens and promoting the production of reproductive hormones. The declining reproductive performance of laying hens in the late laying period may be improved with astaxanthin supplementation.

Astaxanthin improved the storage stability of docosahexaenoic acid-enriched eggs by inhibiting oxidation of non-esterified poly-unsaturated fatty acids.

This study assessed the potential and mechanism of action of astaxanthin, to improve the stability of docosahexaenoic acid (22:6(n-3); DHA) enriched egg products, during storage at 4 °C. The reduction in DHA content after 42 days of storage in astaxanthin-DHA eggs (from hens fed supplemental astaxanthin and DHA) was <3%, whereas the reduction in regular-DHA eggs (hens fed DHA only) was over 17%. Astaxanthin also decreased production of oxidation products including 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and malondialdehyde in eggs during storage, thus markedly improving the oxidative stability of DHA-enriched eggs. The yolk lipidomic profile showed higher intensities for most DHA-containing lipids, especially DHA-phosphatidylcholine, DHA-phosphatidylethanolamine and DHA-non-esterified fatty acid, compared with regular-DHA eggs. Astaxanthin acts primarily by suppressing oxidation of DHA-non-esterified fatty acid, which minimizes the degradation of DHA and appears to be the primary protection mode of yolk DHA during storage.

Multi-Omics Profiling Reveals Se Deficiency-Induced Redox Imbalance, Metabolic Reprogramming, and Inflammation in Pig Muscle.

BACKGROUND: Nutritional muscle dystrophy is associated with selenium (Se) deficiency; however, the underlying mechanism remains unclear. OBJECTIVES: This study aimed to understand the crosstalk among redox status, energy metabolism, and inflammation in nutritional muscle dystrophy induced by dietary Se deficiency. METHODS: Eighteen castrated male pigs (Yorkshire, 45 d old) were fed Se-deficient (Se-D; 0.007 mg Se/kg) or Se-adequate (Se-A; in the form of selenomethionine, 0.3 mg Se/kg) diets for 16 wk. The muscle Se concentrations; antioxidant capacity; and gene expression, transcriptome, global proteome, metabolome, and lipidome profiles were analyzed. The transcriptome, metabolome, and proteome profiles were analyzed with biostatistics, bioinformatics, and pathway enrichment analysis; other data were analyzed with Student's 2-sided t tests. RESULTS: The muscle Se content in the Se-D group was 96% lower than that in the Se-A group (P < 0.05). The activity of glutathione peroxidase (GPX) and thioredoxin reductase (TXNRD) in the Se-D group was 42%-69% lower than that in the Se-A group (P < 0.05). The mRNA levels of 10 selenoprotein genes were 25%-84% lower than those in the Se-A group (P < 0.05). Multi-omics analyses indicated that the levels of 1378 transcripts, 83 proteins, 22 metabolites, and 55 lipid molecules were significantly altered in response to Se deficiency. Se deficiency-induced redox imbalance led to muscle central carbon and lipid metabolism reprogramming, which enhanced the glycolysis pathway and decreased phospholipid synthesis. Inflammation and apoptosis were observed in response to Se deficiency-induced muscle oxidative stress, which may have been associated with extracellular matrix (ECM) remodeling, suppressed focal adhesion and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, and activation of the NF-κB signaling pathway. CONCLUSIONS: These results contributed to understanding the crosstalk among redox, energy metabolism, and inflammation in Se deficiency-induced muscle dystrophy in pigs, and may provide intervention targets for muscle disease treatment.

A naphthimide fluorescent probe for the detection of selenols in selenium-enriched Tan sheep.

An "off-on" fluorescent probe, Nap-DNB, which is based on naphthimide, was designed and developed for the detection of biological selenols in vitro. We have adopted a combination of a low-pH detection environment and reaction sites that are more difficult to destroy to avoid the interference of a large number of biological thiols in biological samples. Nap-DNB can completely respond to selenocysteine within 15 mins, with a detection limit of 92 nM. Nap-DNB was successfully used for the detection of selenols in the serum, liver, and longissimus dorsi of selenium-enriched Tan sheep. Through comparison, we found that the detection of selenols by the Nap-DNB is similar to that by thioredoxin reductase and glutathione peroxidase in a commercial kit method. Nap-DNB can be used for the detection of selenols in selenium-enriched Tan sheep.

Selenium Deficiency Induces Pathological Cardiac Lipid Metabolic Remodeling and Inflammation.

SCOPE: Selenium (Se) disequilibrium is closely involved in many cardiac diseases, although its in vivo mechanism remains uncertain. Therefore, a pig model is created in order to generate a comprehensive picture of cardiac response to dietary Se deficiency. METHODS AND RESULTS: A total of 24 pigs are divided into two equal groups, which were fed a diet with either 0.007 mg kg-1 Se or 0.3 mg kg-1 Se for 16 weeks. Se deficiency causes cardiac oxidative stress by blocking glutathione and thioredoxin systems and increases thioredoxin domain-containing protein S-nitrosylation. Energy production is disordered, as free fatty acids are overloaded, the tricarboxylic acid cycle is strengthened, and three respiratory chain proteins enhance S-nitrosylation. Excess free fatty acids lead to increased synthesis of diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, where the latter two are vulnerable to oxidation and causes an increase in malondialdehyde. Moreover, increased palmitic acid enhances de novo ceramide synthesis and accumulation. Additionally, Se deficiency initiates inflammation via cytosolic DNA-sensing pathways, which activates downstream interferon regulatory factor 7 and nuclear factor kappa B. CONCLUSIONS: The present study identifies a lipid metabolic vulnerability and inflammation initiation pathway via Se deficiency, which may provide targets for human redox imbalance-induced cardiac disease treatment.

Effects of chlortetracycline on growth performance and intestinal functions in weaned piglets.

AIM: Weaning stress can cause serious damage to piglet's health. Chlortetracycline (CTC) is widely used to ameliorate weaning stress and prevent infectious diseases in weaned piglets. However, antibiotics as growth promoters have to be limited because of increased antimicrobial resistance. In this study, we evaluated the effects of CTC on growth performance and intestinal functions in order to provide evidence for seeking antibiotic substitutes in weaned piglets. METHODS AND RESULTS: A total of 20 weaned piglets were fed a basal diet or a diet supplemented with 75 mg/kg CTC. CTC decreased the crypt depth and increased the ratio of villus height to crypt depth, whilst failing to affect growth performance and serum biochemical parameters and cytokines. 16S rRNA sequencing suggested that CTC supplementation had no effect on the diversity and composition of colonic microbiota. CONCLUSION: We speculated that gut microbiota is no longer sensitive to a low concentration of CTC due to the long-term use and low bioavailability of CTC in weaned piglets.

Effects of duration and supplementation dose with astaxanthin on egg fortification.

Long-term and graded dose of astaxanthin supplementation in laying hen's diet was assessed for egg fortification. Five groups of laying hens with 8 replications each were fed for 24 wk with diet supplemented astaxanthin at 0 mg/kg (control), 7.1 mg/kg, 14.2 mg/kg, 21.3 mg/kg, and 42.6 mg/kg (Basal, A7, A14, A21, and A42, respectively). The performance of laying hens, egg quality, astaxanthin concentration as well as conversion efficiency and geometric isomers proportion in yolks were assessed on wk 8 and 24. One-way analysis of variance (ANOVA) and linear and quadratic regression analyses were used to evaluate the dose effect. In parallel, the Student's t test compared the values between wk 8 and wk 24 of test within a group. Overall, the results revealed that neither production performance nor egg physical quality was affected by astaxanthin dose level and feeding duration. Following the supplementation dose, the redness of yolks (a*) increased (P < 0.001). But, the a* score in A42 (23.48) was just 3-folds the a* score in A7 (8.89). Concentration of astaxanthin in eggs was dose-level dependent showing a linear relationship (P < 0.001) with a slight declination observed in all groups on wk 24 compared to wk 8. The deposition rate of astaxanthin into egg yolk was higher in A21 and A42. The proportion of geometric isomers in egg yolk were not affected by the feeding duration. As the supplementation dose increased, all-trans isomer proportion gradually decreased in the egg yolk, while 13-cis isomer proportion rose. It was concluded that astaxanthin is an efficient carotenoid for egg fortification, which can be supplemented in diet up to 42.6 mg/kg for 24 wk without compromising the performance of laying hens or physical quality of eggs. This appreciably affects the egg yolk color and confers a better accumulation of total astaxanthin and cis isomers into eggs as the supplementation dose increases.

Effect of Replacing in-Feed Antibiotic Growth Promoters with a Combination of Egg Immunoglobulins and Phytomolecules on the Performance, Serum Immunity, and Intestinal Health of Weaned Pigs Challenged with Escherichia coli K88.

The study was conducted to investigate the effects of replacing antibiotic growth promoters (AGPs) with an egg immunoglobulin (IgY) combined with phytomolecules (PM) on the growth rate, serum immunity, and intestinal health of weaned pigs challenged with Escherichia coli K88 (E. coli K88). A total of 192 piglets were weaned at 28 days old with an average weight of 7.29 (± 0.04) kg. They were randomly divided into four treatments containing eight replicates with six piglets per replicate. The treatment groups were NC and PC fed a basal diet, AGP fed a basal diet supplemented with 75 mg/kg chlortetracycline, 50 mg/kg oxytetracycline calcium, and 40 mg/kg zinc bacitracin, IPM fed a basal diet supplemented with IgY at dose of 2.5 g/kg and 1.0 g/kg and PM at dose of 300 mg/kg and 150 mg/kg during days 1 to 17 and 18 to 42, respectively. On days 7 to 9 of the experiment, piglets in the PC, AGP, and IPM groups were orally challenged with 20 mL E. coli K88 (109 CFU/mL), while piglets in the NC group were challenged with 20 mL medium without E. coli K88. The E. coli K88 challenge model was successful as the incidence of post-weaning diarrhea (PWD) of piglets challenged with E. coli K88 was significantly higher than that of those unchallenged piglets during the challenge time (days 7 to 9) and days 1 to 7 of post-challenge (p < 0.05). A diet with combinations of IgY and PM and AGPs significantly decreased the incidence of PWD during the challenge time and days 1 to 7 of post-challenge (p < 0.05) compared to the PC group and significantly improved the ratio of feed to weight gain (F:G) during days 1 to 17 of the experiment compared to the NC and PC groups (p < 0.05). In comparison with the PC group, piglets in the IPM group had significantly higher serum levels of IgA, IgG, and IgM (p < 0.05), but lower serum IL-1ß on day 17 of experiement (p < 0.05). Besides, diet supplementation with AGP significantly decreased serum IL-1ß, IL-6, and TNF-α on days 17 and 42 (p < 0.05) with comparison to the PC group. Piglets in the IPM group showed a significantly lower level of fecal coliforms (p < 0.05), but a higher villus height of jejunum and ileum and higher ratio of villus height to crypt depth of duodenum and jejunum (p < 0.05) than those piglets in the PC group. In summary, diet supplementation with a mixture of IgY and PM decreased the incidence of PWD and coliforms, increased feed conversion ratio, and improved intestinal histology and immune function.

Selenium Deficiency-Induced Pancreatic Pathology Is Associated with Oxidative Stress and Energy Metabolism Disequilibrium.

Selenium (Se) is an essential micronutrient that plays a crucial role in development and physiological processes. The present study aimed to investigate the effects of Se deficiency on pancreatic pathology and the potential mechanism in pigs. Twenty-four castrated male Yorkshire pigs were divided into two groups and fed a Se-deficient diet (0.007 mg Se/kg) or a Se-adequate diet (0.3 mg Se/kg) for 16 weeks. The serum concentrations of insulin and glucagon, Se concentration, histologic characteristics, apoptotic status, antioxidant activity, free radical content, and major metabolite concentrations were analyzed. The results showed that Se deficiency reduced the concentrations of insulin and glucagon in the serum and of Se in pancreas, decreased the number of islets and cells in the local islets, and induced pancreatic apoptosis. Se deficiency caused a redox imbalance, which led to an increase in the content of free radicals and decreased the activity of antioxidant enzymes. Of 147 targeted metabolites judged to be present in pancreas, only hypotaurine and D-glucuronic acid had differential concentrations with the false discovery rate < 0.05. Pathway analysis using metabolites with differential expression (unadjusted P < 0.05, fold change > 1.4 or < 0.67) found that 8 glycolytic metabolites were significantly increased by Se-deficient, whereas most of the tricarboxylic acid cycle and pentose phosphate pathway metabolites were not significantly changed. Our studies indicated that Se deficiency-induced pancreatic pathology was associated with oxidative stress and enhanced activity of glycolysis, which may provide gaining insight into the actions of Se as a diabetogenic factor.

Modified EMR-lipid method combined with HPLC-MS/MS to determine folates in egg yolks from laying hens supplemented with different amounts of folic acid.

Egg yolks are a good source of folates. However, the method for analyzing the naturally occurring folates in egg yolks is complicated and time-consuming. In this study, a simplified pre-treatment method followed by validated HPLC-MS/MS was developed to determine native folates in eggs from laying hens treated with different amounts of folic acid. The modified enhanced matrix removal -lipid method to purify samples showed good performance in lipid elimination, reduction of steps and time savings. According to experimental analysis, yolks contained total folate amounts ranging from 147 to 760 µg/100 g when laying hens' diet was supplemented with folic acid from 0 to 10 mg/kg. Four folate vitamers were detected in egg yolks: 5-methyltetrahydrofolate accounted for 91-98% of total folates, whereas folic acid, 5-formyltetrahydrofolate and 10-formylfolic acid together accounted for 2-9%. Therefore, laying hens efficiently converted folic acid in feed into 5-methyltetrahydrofolate in eggs with little folic acid deposition.

Combinatory Effect of ALA-PDT and Itraconazole Treatment for Trichosporon asahii.

BACKGROUND AND OBJECTIVES: Trichosporiosis is an opportunistic infection that includes superficial infections, white piedra, hypersensitivity pneumonitis, and invasive trichosporonosis. The effect of antifungal agents against these infections is largely weakened by drug resistance and biofilms-related virulence. Photodynamic therapy (PDT) is a new therapeutic approach developed not only to combat cancerous lesions but also to treat infectious diseases such as fungal infections. However, there are few studies on the antimicrobial mechanism of 5-aminolevulinic acid PDT (ALA-PDT) in treating Trichosporon. In this work, we explored the possibility of combining ALA-PDT with an antifungal agent to enhance the therapeutic efficacy of Trichosporon asahii (T. asahii) in a clinical setting and in vitro. STUDY DESIGN/MATERIALS AND METHODS: The biofilms of T. asahii were constructed by a 96-well plate-based method in vitro. The planktonic and adherent T. asahii were exposed to different concentrations of photosensitizers and different light doses. After PDT treatment, counting colony-forming units and tetrazolium (XTT) reduction assay were used to estimate the antifungal efficacy. The minimal inhibitory concentration of itraconazole before and after PDT treatment was determined by the broth dilution method, and XTT viability assay was used to detect and evaluate the synergistic potential of ALA-PDT and itraconazole combinations in inhibiting biofilms. Scanning electron microscopy (SEM) was performed to assess the disruption of biofilms. RESULTS: Using combination therapy, we have successfully treated a patient who had a T. asahii skin infection. Further in vitro studies showed that the antifungal effect of ALA-PDT on planktonic and adherent T. asahii was dependent on the concentration of ALA and light dosages used. We also found that the sensitivity of both planktonic and biofilm cells to itraconazole were increased after ALA-PDT. Synergistic effect were observed for biofilms in ALA-PDT and itraconazole-combined treatment. The disruption of biofilms was confirmed by SEM, suggesting that ALA-PDT effectively damaged the biofilms and the destruction was further enhanced by ALA-PDT combination of antifungal agents. CONCLUSIONS: In conclusion, these data suggest that ALA-PDT could be an alternative strategy for controlling infections caused by Trichosporon. The combination therapy of ALA-PDT with itraconazole could result in increased elimination of planktonic cells and biofilms compared with single therapy. All these findings indicate that it could be a promising treatment against trichosporonosis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.