Glycocholic Acid Research Articles

Molecular mechanisms of hepatoprotective effect of tectorigenin against ANIT-induced cholestatic liver injury: Role of FXR and Nrf2 pathways.

Cholestatic liver injury is caused by toxic action or allergic reaction, resulting in abnormality of bile formation and excretion. Few effective therapies have become available for the treatment of cholestasis. Herein, we found that tectorigenin (TG), a natural isoflavone, showed definite protective effects on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury, significantly reversing the abnormality of plasma alanine/aspartate aminotransferase, total/direct bilirubin and alkaline phosphatase, as well as hepatic reactive oxygen species, catalase and superoxide dismutase. Importantly, the targeted metabolomic determination found that BA homeostasis could be well maintained in TG-treated cholestatic mice, especially the levels of glycocholic acid, tauromuricholic acid, taurocholic acid, taurolithocholic acid, tauroursodeoxycholic acid and taurodeoxycholic acid. Overall, primary/secondary and amidated/unamidated bile acid (BA) levels were significantly altered upon ANIT stimulation but could be restored by TG intervention to certain extents. In addition, TG boosted the expression of farnesoid x receptor (FXR), which in turn upregulated multidrug resistance protein 2 (MRP2) and bile salt export pump (BSEP) to accelerate the excretion of BA. Meanwhile, TG enhanced the expression of Nrf2 and its upstream genes PI3K/Akt and downstream target genes HO-1, NQO1, GCLC and GCLM to strengthen the antioxidant capacity. Taken together, TG plays a vital role in maintaining BA homeostasis and ameliorating cholestatic liver injury through regulating FXR-mediated BA efflux and Nrf2-mediated antioxidative pathways.

Metabolomic profile of patients on levothyroxine treatment for hypothyroidism.

Hypothyroidism is clinically characterized by a decrease in levels of the circulating thyroid hormones namely thyroxine and triiodothyronine. The main treatment for hypothyroidism is thyroid hormone replacement using levothyroxine to normalize serum thyroid hormone levels. In this study, we explored the metabolic changes in the plasma of patients with hypothyroidism after reaching a euthyroid state with levothyroxine treatment. Plasma samples from 18 patients diagnosed as overt hypothyroidism were collected before and after levothyroxine treatment upon reaching a euthyroid state and were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate and univariate analyses evaluated data to highlight potential metabolic biomarkers. Liquid chromatography-mass spectrometry-based metabolomics revealed a significant decrease in the levels of ceramide, phosphatidylcholine, triglycerides, acylcarnitine, and peptides after levothyroxine treatment; this could indicate a change in the fatty acid transportation system and an enhanced β-oxidation, compared with a hypothyroid state. At the same time, the decrease in the peptides suggested a shift in protein synthesis. In addition, there was a considerable rise in glycocholic acid following therapy, suggesting the involvement of thyroid hormones in stimulating bile acid production and secretion. A metabolomic analysis of patients with hypothyroidism revealed significant changes in several metabolites and lipids after treatment. This study showed the value of the metabolomics technique in providing a complementary understanding of the pathophysiology of hypothyroidism and as a crucial tool for examining the molecular impact of levothyroxine treatment on hypothyroidism. It was an important tool for investigating the therapeutic effects of levothyroxine on hypothyroidism at the molecular level.

Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression

Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.

The effect of a preparation containing glycocholic acid on the biocidal efficacy of sodium hypochlorite in a biofilm laboratory model.

This study assessed the antimicrobial effect of sodium hypochlorite (NaOCl) mixtures combined with Keratobacter (KB) using an engineered biofilm root canal model. Clinical and reagent grade NaOCl were mixed with KB (9:1-vol/vol) to assess pH values over 1 min to select the ideal solution with a pH just below the pKa of hypochlorous acid. The samples were randomly divided into five groups: 1% and 4% NaOCl reagents, a mixture of NaOCl:KB using 1% and 4% NaOCl reagents and distilled water. Outcome measures were colony-forming units (CFUs/mL) and positive/negative cultures. No significant differences were observed in the pairwise comparisons between 1%, 4% NaOCl and 4% NaOCl+KB for the outcome CFUs/mL. Only 4% NaOCl presented with negative cultures in all samples, whereas 1% NaOCl and 4% NaOCl+KB had similar results (54% vs. 40%). The addition of KB has a limited effect on the antimicrobial efficacy of 4% NaOCl in this laboratory model.

Effects of Anemoside B4 on Plasma Metabolites in Cows with Clinical Mastitis.

Anemoside B4 has a good curative effect on cows with CM; however, its impact on their metabolic profiles is unclear. Based on similar somatic cell counts and clinical symptoms, nine healthy dairy cows and nine cows with CM were selected, respectively. Blood samples were collected from cows with mastitis on the day of diagnosis. Cows with mastitis were injected with anemoside B4 (0.05 mL/kg, once daily) for three consecutive days, and healthy cows were injected with the same volume of normal saline. Subsequently, blood samples were collected. The plasma metabolic profiles were analyzed using untargeted mass spectrometry, and the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in serum were evaluated via ELISA. The cows with CM showed increased concentrations of IL-1β, IL-6, and TNF-α (p < 0.05). After treatment with anemoside B4, the concentrations of IL-1β, IL-6, and TNF-α were significantly decreased (p < 0.01). Untargeted metabolomics analysis showed that choline, glycocholic acid, PC (18:0/18:1), 20-HETE, PGF3α, and oleic acid were upregulated in cows with CM. After treatment with anemoside B4, the concentrations of PC (16:0/16:0), PC (18:0/18:1), linoleic acid, eicosapentaenoic acid, phosphorylcholine, and glycerophosphocholine were downregulated, while the LysoPC (14:0), LysoPC (18:0), LysoPC (18:1), and cis-9-palmitoleic acid were upregulated. This study indicated that anemoside B4 alleviated the inflammatory response in cows with CM mainly by regulating lipid metabolism.

Identification of a potential prognostic plasma biomarker of acute ischemic stroke via untargeted LC-MS metabolomics.

Strokeisthesuddendeathofbraincellsinalocalized areaduetoan inadequatebloodflow or blood vessel rupture, and it seriously affects the quality of life. The metabolite biomarkers are needed for predicting the functional outcome of acute ischemic stroke (AIS). To identify biomarkers for AIS, untargeted LC/MS metabolomics was performed on plasma samples from subjects with favorable prognosis (mRS ≤ 2) and unfavorable prognosis (mRS>2). The identified markers were further absolutely quantified by a targeted MRM approach. There were 10 upregulated and 26 downregulated markers. Among these candidates, one was successfully identified as glycocholic acid and then absolutely quantified in plasma samples. Glycocholic acid could discriminate between subjects with favorable and unfavorable prognosis with an area under the curve (AUC) of 0.68 and odds ratio of 5.88. Glycocholic acid was identified as a potential plasma metabolite marker of non-progressive outcomes after ischemic stroke and could serve as predictive prognostic markers for clinical acute stroke outcomes.

Bifidobacterium longum LBUX23 Isolated from Feces of a Newborn; Potential Probiotic Properties and Genomic Characterization.

Bifidobacterium longum is considered a microorganism with probiotic potential, which has been extensively studied, but these probiotic effects are strain dependent. This work aims to characterize the probiotic potential, based on the biochemical and genomic functionality, of B. longum LBUX23, isolated from neonates' feces. B. longum LBUX23 contains one circular genome of 2,287,838 bp with a G+C content of 60.05%, no plasmids, no CRISPR-Cas operon, possesses 56 tRNAs, 9 rRNAs, 1 tmRNA and 1776 coding sequences (CDSs). It has chromosomally encoded resistance genes to ampicillin and dicloxacillin, non-hemolytic activity, and moderate inhibition of Escherichia coli ATCC 25922 and to some emergent pathogen's clinical strains. B. longum LBUX23 was able to utilize lactose, sucrose, fructooligosaccharides (FOS), and lactulose. The maximum peak of bacterial growth was observed in sucrose and FOS at 6 h; in lactose and lactulose, it was shown at 8 h. B. longum LBUX23 can survive in gastrointestinal conditions (pH 4 to 7). A decrease in survival (96.5 and 93.8%) was observed at pH 3 and 3.5 during 120 min. argC, argH, and dapA genes could be involved in this tolerance. B. longum LBUX23 can also survive under primary and secondary glyco- or tauro-conjugated bile salts, and a mixture of bile salts due to the high extracellular bile salt hydrolase (BSH) activity (67.3 %), in taurocholic acid followed by taurodeoxycholic acid (48.5%), glycocholic acid (47.1%), oxgall (44.3%), and glycodeoxycholic acid (29.7%) probably due to the presence of the cbh and gnlE genes which form an operon (start: 119573 and end: 123812). Low BSH activity was determined intracellularly (<7%), particularly in glycocholic acid; no intracellular activity was shown. B. longum LBUX23 showed antioxidant effects in DPPH radical, mainly in intact cells (27.4%). In the case of hydroxyl radical scavenging capacity, cell debris showed the highest reduction (72.5%). In the cell-free extract, superoxide anion radical scavenging capacity was higher (90.5%). The genome of B. longum LBUX23 contains PNPOx, AhpC, Bcp, trxA, and trxB genes, which could be involved in this activity. Regarding adherence, it showed adherence up to 5% to Caco-2 cells. B. longum LBUX23 showed in vitro potential probiotic properties, mainly in BSH activity and antioxidant capacity, which indicates that it could be a good candidate for antioxidant or anti-cholesterol tests using in vivo models.

Fast profiling of primary, secondary, conjugated, and sulfated bile acids in human urine and murine feces samples.

Bile acids (BAs) are a complex class of metabolites that have been described as specific biomarkers of gut microbiota activity. The development of analytical methods allowing the quantification of an ample spectrum of BAs in different biological matrices is needed to enable a wider implementation of BAs as complementary measures in studies investigating the functional role of the gut microbiota. This work presents results from the validation of a targeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 28 BAs and six sulfated BAs, covering primary, secondary, and conjugated BAs. The analysis of 73 urine and 20 feces samples was used to test the applicability of the method. Concentrations of BAs in human urine and murine feces were reported, ranging from 0.5 to 50nmol/g creatinine and from 0.012 to 332nmol/g, respectively. Seventy-nine percent of BAs present in human urine samples corresponded to secondary conjugated BAs, while 69% of BAs present in murine feces corresponded to primary conjugated BAs. Glycocholic acid sulfate (GCA-S) was the most abundant BA in human urine samples, while taurolithocholic acid was the lowest concentrated compound detected. In murine feces, the most abundant BAs were α-murocholic, deoxycholic, dehydrocholic, and β-murocholic acids, while GCA-S was the lowest concentrated BA. The presented method is a non-invasive approach for the simultaneous assessment of BAs and sulfated BAs in urine and feces samples, and the results will serve as a knowledge base for future translational studies focusing on the role of the microbiota in health.

The K+ and Mg2+ decreased the adsorption of soy hull polysaccharides on glycocholic acid in vitro

Abstract This study aimed to explore the effect of ion on the interaction between soy hull polysaccharides (SHP) and glycocholic acid (GCA). The determination of bile acids (BAs) binding rate, FT-IR, and zeta potential revealed that the binding rate of SHP to GCA (fell about 14 %), hydrogen bond peak area (fell about 149), and zeta potential (fell about 13 %) showed a sharp downward trend after K+ and Mg2+ treatment. However, the apparent viscosity increased and the chain structure became closer, as detected by shear rheology and AFM analysis. The root mean square deviation, radius of gyration, and root mean square fluctuation levels were estimated through molecular dynamic simulations, revealing that adding mixed ions decreased the stability of the SHP–GCA complex at 50 ns. Therefore, it was meaningful to study the effect of ion species in the intestinal environment on the binding of dietary fibers to BAs. The findings might guide the selection of other food types during polysaccharide intake.

Bile acid metabolites in early pregnancy and risk of gestational diabetes mellitus: Results from a prospective cohort study.

To evaluate the associations of plasma bile acid metabolites, especially in early pregnancy, with gestational diabetes mellitus (GDM) risk among pregnant women. Plasma concentrations of 15 bile acid metabolites were measured in 645 women at early pregnancy from the Jiashan Birth Cohort using a liquid chromatography-tandem mass spectrometry metabolomics platform. Using logistic and cubic spline models, we examined associations between baseline plasma bile acid metabolites and GDM risk during mid-late pregnancy. A meta-analysis of prospective studies of bile acid and GDM risk was performed. The linear and nonlinear univariate models identified eight metabolites associated with GDM, including cholic acid, taurocholic acid (TCA), glycocholic acid, glycochenodeoxycholic acid, deoxycholic acid, lithocholic acid (LCA), ursodeoxycholic acid and taurolithocholic acid (all P <0.05). Multivariable analysis indicated that TCA and LCA levels were positively (odds ratio [OR] 2.07, 95% confidential interval [CI] 1.05, 3.96; P = 0.030) and negatively (OR 0.83, 95% CI 0.68, 1.01; P = 0.065) associated with GDM, respectively, after adjusting for confounders. The TCA-GDM association showed a positive linear shaped relationship (OR 2.07, 95% CI 1.05, 3.96; P = 0.030); while LCA was negatively related with GDM risk in linearity (OR 0.83, 95% CI 0.68, 1.01; P = 0.065). The meta-analysis of five studies showed a consistent bile acid and GDM association, with a risk ratio (RR) of 2.43 (1.95, 3.03). This study indicated that, the levels of circulating bile acids in early pregnancy were associated with risk of GDM, independent of GDM risk factors. Most GDM-associated bile acids were primary conjugated and secondary unconjugated bile acids.

Integrated Microbiome and Metabolomic Analysis Reveal the Repair Mechanisms of Ovalbumin on the Intestine Barrier of Colitis Mice.

The development and progression of colitis would detrimentally destroy the intestine barrier. However, there remains a paucity of evidence on whether ovalbumin (OVA) can be used as a nutritional food protein to repair the intestinal barrier. In this study, the repairing mechanism of OVA on intestinal barrier was thoroughly investigated by gut microbiota and untargeted metabolomics techniques. The findings demonstrated that OVA reduced intestinal permeability and restored mucin (0.75 ± 0.06) and tight junction (TJ) protein (0.67 ± 0.14) expression in colitis mice caused by 3% dextran sulfate sodium (DSS). In addition, the inflammation response and oxidative stress were also attenuated. The intake of OVA upregulated the abundance of Lactobacillaceae (7.60 ± 3.34%) and Akkermansiaceae (10.39 ± 5.97%). Furthermore, OVA upregulated the abundance of inosine (6.06 ± 0.36%), putrescine (4.14 ± 0.20%), and glycocholic acid (5.59 ± 0.23%) in colitis mice through ATP binding cassette (ABC) transporters and bile secretion pathways. In summary, our findings revealed that OVA could maintain intestinal health, which may provide crucial insights for preventing and treating intestinal diseases.

The Expression Levels of Genes Responsible for the Enzymatic Activity of Bile Salt Hydrolase (BSH) and the Relationship of Cholesterol Assimilation in L. plantarum and L. paracasei.

The bile salt hydrolase (BSH) activity is responsible for the cholesterol-lowering effect of the probiotic strains. The present study aimed to investigate the relationship between bsh gene-expression (GE) levels responsible for the BSH activity and the parameters of bile salt resistance of different Lactobacillaceae species. Accordingly, 11 Lactobacillaceae family strains with high cholesterol assimilation ratio (49.21-68.22%) determined by the o-phthalaldehyde method selected from 46 Lactobacillaceaespecies was evaluated for their features including acid tolerance, bile tolerance, and BSH activity. All tested strains survived at pH 2 medium and 0.3% (w/v) bile salt and showed positive BSH activity for glycocholic acid (GCA) and taurocholic acid (TCA). BSH gene expression was performed to provide clear information and to identify the key genes responsible for BSH activity. bsh3 genes were found highest GE level (P < 0.05) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains. The results showed that high cholesterol assimilation ratio were closely correlated with BSH activity and the parameters of bile salt resistance. The results of this study will support the development of a new approach based on phenotypic and genetic analysis to determine the bile salt parameters. The study will be useful for the selection of Lactobacillus strains with high bile salt resistance.

Effects of donepezil treatment on plasma and urine metabolites in amyloid beta-induced Alzheimer's disease rats

Accumulated clinical and biomedical evidence suggests that abnormalities in systemic metabolic processes such as fatty acid and amino acid metabolism can affect the brain function and behavior of various central nervous system diseases such as Alzheimer's disease (AD). In this study, metabolic profiling was used to investigate changes in plasma and urine metabolites following stereotactic injection of amyloid β (Aβ) and treatment with donepezil in rats. Aβ causes cognitive impairment, while donepezil treatment successfully improves memory impairment. Donepezil improves Aβ-induced plasma fatty acid and bile acid metabolism disorders, as well as Aβ-induced urine phenylalanine and tryptophan metabolism disorders in rats. More specifically, the plasma fatty acids improved by donepezil include alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, arachidonic acid, oleic acid, and palmitic acid, among others. Additionally, donepezil significantly restored the downregulation of bile acids such as ursodeoxycholic acid, cholic acid, and glycocholic acid caused by Aβ. As for urine metabolites, phenylacetylglycine, epinephrine, and other phenylalanine metabolites, as well as kynurenic acid, xanthurenic acid, and other tryptophan metabolites, were worsened by Aβ and improved by donepezil. These findings suggest that the cognitive impairment induced by Aβ and the improvement by donepezil are associated with changes in metabolic disorders in rats. This study provides basic data for the effects of Aβ and donepezil on plasma and urine metabolites in Aβ-induced AD rat models.

Signatory metabolomics biomarkers of stress, anxiety, and depression: a proof of concept for precision health among university students: A cross-sectional study

Purpose: The highly competitive nature of tertiary education and the pressure to perform academically have increased psychological morbidity like emotional distress. Untargeted metabolomics was used to analyze serum samples of university students for biomarkers and perturbated metabolism due to stress, anxiety, and depression (SAD).Methods: Depression, Anxiety, Stress Scale 21 (DASS-21) was used to assess the severity of SAD in university students. The metabolite fingerprint of each subject was obtained using liquid chromatography-mass spectrometry quadrupole time-of-flight (LC/MS QTOF). The signature metabolites for each trait were determined by projections to latent structures discriminant analysis (PLS-DA) with variable importance for the projection (VIP) score &gt; 1.0 (P&lt;0.05) and subjected to analysis using the area under the receiver operating characteristic curve (AUROC). Potential biomarkers with an area under the curve (AUC) value exceeding 0.65 were identified.Results: Various groups of glycerophospholipids were upregulated in the studied traits. On the other hand, metabolites such as glycocholic acid was upregulated in depression, while hypoxanthine was upregulated in anxiety, and PE-Cer(d14:1(4E)/22:1(13Z)) was upregulated in stress.Conclusion: To our knowledge, this is the first study to assess the relationship of the differentially expressed metabolites in university students of different categories of SAD using the DASS-21 screening tool in Malaysia as we move forward with precision health.

The effect of Sichuan pepper on gut microbiota in mice fed a high-sucrose and low-dietary fibre diet

Sichuan pepper (Zanthoxylum bungeanum, HJ), a spice widely used in China, has antioxidative, anti-inflammatory, antibacterial, and anti-obesity properties. In this study, to confirm the value of HJ as a functional food, the in vitro antioxidant and bile acid-lowering capacities, as well as the effects on caecal microbiota, were compared with those of cumin (Cuminum cyminum, CM) and coriander (Coriandrum sativum, CR) seeds in Institute of Cancer Research (ICR) mice fed a high-sucrose and low-dietary fibre diet. The total phenolic content, superoxide anion radical-scavenging capacity, and Fe-reducing power of the HJ aqueous solution were higher than those of CM and CR (p < 0.05). The bile acid (taurocholic, glycocholic, and deoxycholic acids)-lowering capacity of the HJ suspension was also higher than those of CM and CR. Compared with mice fed a control diet (no fibre, NF), caecal Lactobacillus gasseri- and Muribaculum intestinale-like bacteria were higher in mice fed a diet containing 5% (w/w) of CM, CR, or HJ for 14days. Bifidobacterium pseudolongum-, Lactobacillus murinus/animalis-, and Faecalibaculum rodentium-like bacteria were significantly increased, while Desulfovibrio-like bacteria were significantly decreased in the HJ group. In addition, CM and HJ may benefit specific metabolic functions of gut microbiota, such as starch, sucrose, and tyrosine metabolism. The tumour necrosis factor (TNF-α) concentration in the spleen tissue of ICR mice was decreased by the intake of spices. However, there were no changes in interleukin-2 (IL-2) and IL-10 levels in HJ fed mice. These results suggested that HJ has potential as a functional food related to gut microbiota. KEY POINTS: • Bididobacterium and Faecalibaculum in mice gut microbiota are increased by Sichuan pepper (HJ). • Desulfovibrionaceae, an inflammatory LPS producer, in mice gut microbiota is decreased by HJ. • HJ decreases pro-inflammatory TNF both in murine spleen tissue and in vitro macrophages.

Characterization of Calculus bovis by principal component analysis assisted qHNMR profiling to distinguish nefarious frauds

A new approach is developed for the reliable classification of Calculus bovis along with the identification of willfully contaminated C. bovis species and the quantification of unclaimed adulterants. Guided by a principal component analysis, NMR data mining achieved a near-holistic chemical characterization of three types of authenticated C. bovis, including natural C. bovis (NCB), in vitro cultured C. bovis (Ivt-CCB), and artificial C. bovis (ACB). In addition, species-specific markers used for quality evaluation and species classification were confirmed. That is, the content of taurine in NCB is near negligible, while choline and hyodeoxycholic acid are characteristic for identifying Ivt-CCB and ACB, respectively. Besides, the peak shapes and chemical shifts of H2-25 of glycocholic acid could assist in the recognition of the origins of C. bovis. Based on these discoveries, a set of commercial NCB samples, macroscopically identified as problematic species, was examined with deliberately added sugars and outliers discovered. Absolute quantification of the identified sugars was realized by qHNMR using a single, nonidentical internal calibrant (IC). This study represents the first systematic study of C. bovis metabolomics via an NMR-driven methodology, which advances the toolbox for quality control of TCM and provides a more definitive reference point for future chemical and biological studies of C. bovis as a valuable materia medica.

Effects of selenium oxide nanoparticles on the morphofunctional state of the liver: Experimental data

Copper smelters are the sources of emission of complex aerosols containing, inter alia, selenium-containing nanoparticles (NPs). It is very difficult to adequately estimate the hazard posed by such particles since available data on them are scarce and have been obtained in comparatively few experimental studies with rather contradicting results. The aim of our study was to determine toxic health effects of selenium-containing nanoparticles more precisely with a focus on liver as a target organ. Liver toxicity following exposure to suspended selenium oxide nanoparticles was investigated in a sub-chronic experiment on outbred male albino rats. The suspension was prepared by laser ablation of 99%-pure selenium plates. We examined ultrastructural changes by electron microscopy, did cytological and histological analyses of the liver, biochemical blood testing and metabolomic blood screening. We observed lesions in the liver and inhibited secretory functions at various levels, from molecular to organismic, in the exposed animals. The microscopic examination showed that the number of normal and normal-vesicular mitochondria in liver cells went down by 7.78 %, p &lt; 0.05; the metabolomic screening established lower levels of glycocholic acid in blood serum, р &lt; 0.001; levels of alanine aminotransferase in blood serum grew by 30 %, p &lt; 0.05; the number of acaryotic hepatocytes demonstrated a 3.1-fold increase, p &lt; 0.05, according to the results of histological assessment of liver specimens. The touch smears of the liver examined showed a 2.2-fold increase in the number of degenerated hepatocytes (p &lt; 0.05). These experimental data can be used to estimate a potential hazard of selenium-containing nanoparticles within social-hygienic monitoring and biomedical predictions of health damage caused by exposure to such NPs. Altered levels of lysophos-phatidylinositol can be a marker of exposure to the examined NPs and necessitate the search for early diagnostic predictors of associated health disorders.

Оценка влияния наночастиц оксида селена на морфофункциональное состояние печени (Экспериментальные данные)

Copper smelters are the sources of emission of complex aerosols containing, inter alia, selenium-containing nanoparticles (NPs). It is very difficult to adequately estimate the hazard posed by such particles since available data on them are scarce and have been obtained in comparatively few experimental studies with rather contradicting results. The aim of our study was to determine toxic health effects of selenium-containing nanoparticles more precisely with a focus on liver as a target organ. Liver toxicity following exposure to suspended selenium oxide nanoparticles was investigated in a sub-chronic experiment on outbred male albino rats. The suspension was prepared by laser ablation of 99%-pure selenium plates. We examined ultrastructural changes by electron microscopy, did cytological and histological analyses of the liver, biochemical blood testing and metabolomic blood screening. We observed lesions in the liver and inhibited secretory functions at various levels, from molecular to organismic, in the exposed animals. The microscopic examination showed that the number of normal and normal-vesicular mitochondria in liver cells went down by 7.78 %, p &lt; 0.05; the metabolomic screening established lower levels of glycocholic acid in blood serum, р &lt; 0.001; levels of alanine aminotransferase in blood serum grew by 30 %, p &lt; 0.05; the number of acaryotic hepatocytes demonstrated a 3.1-fold increase, p &lt; 0.05, according to the results of histological assessment of liver specimens. The touch smears of the liver examined showed a 2.2-fold increase in the number of degenerated hepatocytes (p &lt; 0.05). These experimental data can be used to estimate a potential hazard of selenium-containing nanoparticles within social-hygienic monitoring and biomedical predictions of health damage caused by exposure to such NPs. Altered levels of lysophos-phatidylinositol can be a marker of exposure to the examined NPs and necessitate the search for early diagnostic predictors of associated health disorders.

Intestinal epithelial autophagy is required for the regenerative benefit of calorie restriction.

Calorie restriction can enhance the regenerative capacity of the injured intestinal epithelium. Among other metabolic changes, calorie restriction can activate the autophagy pathway. Although independent studies have attributed the regenerative benefit of calorie restriction to downregulation of mTORC1, it is not known whether autophagy itself is required for the regenerative benefit of calorie restriction. We used mouse and organoid models with autophagy gene deletion to evaluate the contribution of autophagy to intestinal epithelial regeneration following calorie restriction. In the absence of injury, mice with intestinal epithelial-specific deletion of autophagy gene Atg7 (Atg7ΔIEC) exhibit weight loss and histological changes similar to wild-type mice following calorie restriction. Conversely, calorie-restricted Atg7ΔIEC mice displayed a significant reduction in regenerative crypt foci after irradiation compared with calorie-restricted wild-type mice. Targeted analyses of tissue metabolites in calorie-restricted mice revealed an association between calorie restriction and reduced glycocholic acid (GCA) in wild-type mice but not in Atg7ΔIEC mice. To evaluate whether GCA can directly modulate epithelial stem cell self-renewal, we performed enteroid formation assays with or without GCA. Wild-type enteroids exhibited reduced enteroid formation efficiency in response to GCA treatment, suggesting that reduced availability of GCA during calorie restriction may be one mechanism by which calorie restriction favors epithelial regeneration in a manner dependent upon epithelial autophagy. Taken together, our data support the premise that intestinal epithelial Atg7 is required for the regenerative benefit of calorie restriction, due in part to its role in modulating luminal GCA with direct effects on epithelial stem cell self-renewal.NEW & NOTEWORTHY Calorie restriction is associated with enhanced intestinal regeneration after irradiation, but the requirement of autophagy for this process is not known. Our data support the premise that intestinal epithelial autophagy is required for the regenerative benefit of calorie restriction. We also report that luminal levels of primary bile acid glycocholic acid are modulated by epithelial cell autophagy during calorie restriction with direct effects on epithelial stem cell function.

Analysis of the alleviating effect of black bean peel anthocyanins on type 2 diabetes based on gut microbiota and serum metabolome

Black bean peel is rich in various nutrients and exerts therapeutic effects on type 2 diabetes mellitus (T2DM); however, its therapeutic mechanism is still unclear. This study investigated the therapeutic mechanism of black bean peel anthocyanin extract on T2DM from the perspective of gut microbiota and serum metabolome. The black bean peel anthocyanin extract improved blood glucose, oxidative stress and inflammatory responses, and alleviated lipid metabolism disorders in T2DM rats. The abundance of Akkermansia spp., Bacteroidetes spp., Phascolarctobacterium spp., and Turicibacterium spp. were increased in the gut, and the levels of bilirubin, glycocholic acid, lithocholic acid, and glycochenodeoxycholate were increased in serum. The qPCR and western blot results showed that the black bean peel anthocyanin extract improved T2DM and lipid metabolism by regulating the expression of LXR, LKB1, and SREBP-1c. These results provided a new therapeutic direction for T2DM treatment.