Optimizing Cellulase-Limosilactobacillus fermentum ZC529 Synergy Fermentation for Preserving Macadamia integrifolia Pericarp's Potential Use as Antioxidants.

Macadamia integrifolia pericarps (MIP) are byproducts of nut production which are rich in natural antioxidant compounds, making them an excellent source for extracting bioactive compounds. However, the antioxidant compounds in MIP are easily oxidized under natural storage conditions, resulting in significant biomass loss and resource wastage. To preserve the potential of MIP to be used as an antioxidant product, we employed cellulase and Limosilactobacillus fermentum ZC529 (L.f ZC529) fermentation and utilized response surface methodology to optimize the fermentation parameters for mitigating the antioxidant loss. Total antioxidant capacity (T-AOC) was used as the response variable. The fermented MIP water extract (FMIPE) was obtained via ultrasound-assisted extraction, and its biological activity was evaluated to optimize the best fermentation conditions. Results indicated that a cellulase dosage of 0.9%, an L.f ZC529 inoculation size of 4 mL/100 g, and a fermentation time of 7 days were the optimal conditions for MIP fermentation. Compared to spontaneous fermentation, these optimal conditions significantly increased the total phenolic and total flavonoid contents (p < 0.05). T-AOC was 160.72% increased by this optimal fermentation (p < 0.05). Additionally, supplementation with varying concentrations of FMIPE (6.25%, 12.5%, and 25%) increased the T-AOC, SOD activity, and GSH content, and reduced MDA levels of the oxidative-stressed Drosophila melanogaster (p < 0.05). Moreover, 12.5% and 25% of FMIPE treatments elevated CAT activity in the Drosophila melanogaster (p < 0.05). The effects of FMIPE on GSH and MDA in Drosophila melanogaster were equivalent to the 0.5% vitamin C (Vc) treatment. In summary, synergistic fermentation using cellulase and L.f ZC529 effectively preserves the antioxidant activity of the MIP, offering a simple, eco-friendly method to promote the utilization of MIP resources.

Maternal intervention with a combination of galacto-oligosaccharides and hyocholic acids during late gestation and lactation increased the reproductive performance, colostrum composition, antioxidant and altered intestinal microflora in sows.

Introduction: This study was conducted to evaluate the effects of dietary galacto-oligosaccharides (GOS) and hyocholic acids (HCA) during late gestation and lactation on reproductive performance, colostrum quality, antioxidant capacity and gut microbiota in multiparous sows. Methods: A total of 60 healthy multiparous cross-bred sows (Landrace × Yorkshire) were randomly fed 4 groups diets as follows: the basal diets (CTRL group), or the basal diets containing only 600 mg/kg GOS (GOS group), 600 mg/kg GOS + 100 mg/kg HCA (GOS + Low HCA group), and 600 mg/kg + 200 mg/kg HCA (GOS + High HCA group) from d 85 of gestation to weaning. Multiple parameters of sows were determined. Results: There was a trend of shortening the labor process of sows (p = 0.07) in the GOS group and GOS + Low/High HCA group. Compared with the CTRL group, the GOS + Low/High HCA group increased the average piglets weight at birth (p < 0.05), and increased the IgA concentration of colostrum (p < 0.05). In addition, serum triglyceride (TG) concentration was lower (p < 0.05), and serum total antioxidant capacity (T-AOC) was higher (p < 0.05) in the GOS and GOS + Low/High HCA groups than in the CTRL group at farrowing. Serum catalase (CAT) activities was higher in the GOS and GOS + High HCA groups than in the CTRL group at farrowing. The 16S rRNA analysis showed that GOS combination with high-dose HCA shaped the composition of gut microbiota in different reproductive stages (d 107 of gestation, G107; d 0 of lactation, L0; d 7 of lactation, L7). At the phylum level, the relative abundance of Bacteroidota and Desulfobacterota in G107, Bacteroidota, and Proteobacteria in L0, and Planctomycetota in L7 was increased in GOS + High HCA group (p < 0.05). Spearman correlation analysis showed that Streptococcus was positively correlated with the serum TG but negatively correlated with the average piglets weight at birth (p < 0.05). Conclusion: This investigation demonstrated that the administration of galacto-oligosaccharides (GOS) in conjunction with hyocholic acids (HCA), to sows with nutrient restrictions during late gestation and lactation, further improved their antioxidant capacity and milk quality. The observed beneficial effects of GOS + HCA supplementation could potentially be linked to an improvement in gut microbiota disorders of the sows.

Dietary Methionine Restriction Improves Gut Health and Alters the Plasma Metabolomic Profile in Rats by Modulating the Composition of the Gut Microbiota.

Dietary methionine restriction (MetR) offers an integrated set of beneficial health effects, including delaying aging, extending health span, preventing fat accumulation, and reducing oxidative stress. This study aimed to investigate whether MetR exerts entero-protective effects by modulating intestinal flora, and the effect of MetR on plasma metabolites in rats. Rats were fed diets containing 0.86% methionine (CON group) and 0.17% methionine (MetR group) for 6 weeks. Several indicators of inflammation, gut microbiota, plasma metabolites, and intestinal barrier function were measured. 16S rRNA gene sequencing was used to analyze the cecal microbiota. The MetR diet reduced the plasma and colonic inflammatory factor levels. The MetR diet significantly improved intestinal barrier function by increasing the mRNA expression of tight junction proteins, such as zonula occludens (ZO)-1, claudin-3, and claudin-5. In addition, MetR significantly increased the levels of short-chain fatty acids (SCFAs) by increasing the abundance of SCFAs-producing Erysipclotxichaceae and Clostridium_sensu_stricto_1 and decreasing the abundance of pro-inflammatory bacteria Proteobacteria and Escherichia-Shigella. Furthermore, MetR reduced the plasma levels of taurochenodeoxycholate-7-sulfate, taurocholic acid, and tauro-ursodeoxycholic acid. Correlation analysis identified that colonic acetate, total colonic SCFAs, 8-acetylegelolide, collettiside I, 6-methyladenine, and cholic acid glucuronide showed a significant positive correlation with Clostridium_sensu_stricto_1 abundance but a significant negative correlation with Escherichia-Shigella and Enterococcus abundance. MetR improved gut health and altered the plasma metabolic profile by regulating the gut microbiota in rats.

The Roles of Polyamines in Intestinal Development and Function in Piglets.

The gastrointestinal tract plays crucial roles in the digestion and absorption of nutrients, as well as in maintenance of a functional barrier. The development and maturation of the intestine is important for piglets to maintain optimal growth and health. Polyamines are necessary for the proliferation and growth of enterocytes, which play a key role in differentiation, migration, remodeling and integrity of the intestinal mucosa after injury. This review elaborates the development of the structure and function of the intestine of piglets during embryonic, suckling and weaning periods, the utilization and metabolism of polyamines in the intestine, as well as the role of polyamines in intestinal development and mucosal repair. The nutritional intervention to improve intestinal development and functions by modulating polyamine metabolism in piglets is also put forward. These results may help to promote the adaption to weaning in pigs and provide useful information for the development and health of piglets.

Intestinal tryptophan metabolism in disease prevention and swine production.

Tryptophan (Trp) is an essential amino acid that cannot be synthesized by animals. It has been characterized into two different isomers, levorotation-Trp (L-Trp) and dextrorotation-Trp (D-Trp), based on their distinct molecule orientation. Intestinal epithelial cells and gut microbiota are involved in metabolizing L-Trp in the gut via the activation of the kynurenine, serotonin, and indole pathways. However, knowledge regarding D-Trp metabolism in the gut remains unclear. In this review, we briefly update the current understanding of intestinal L/D-Trp metabolism and the function of their metabolites in modulating the gut physiology and diseases. Finally, we summarize the effects of Trp nutrition on swine production at different stages, including growth performance in weaned piglets and growing pigs, as well as the reproduction performance in sows.

Effects of glutamine, glutamate, and aspartate on intestinal barrier integrity and amino acid pool of the small intestine in piglets with normal or low energy diet.

Aspartate (asp), glutamate (glu), and glutamine (gln) are the major energy fuels for the small intestine, and it had been indicated in our previous study that the mix of these three amino acid supplementations could maintain intestinal energy homeostasis. This study aimed to further investigate whether the treatment of gln, glu, and asp in low energy diet affects the intestinal barrier integrity and amino acid pool in weaning piglets. A total of 198 weaned piglets were assigned to 3 treatments: control (basal diet + 1.59% L-Ala); T1 (basal diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp); and T2 (low energy diet + 1% L-Gln + 0.5% L-Glu + 0.1% L-Asp). The blood, jejunum, and ileum were obtained on day 5 or on day 21 post-weaning, respectively. Our results showed that T1 and T2 treatments increased the abundances of occludin, claudin-1, and claudin-3 in the small intestine while decreasing the serum diamine oxidase (DAO) and D-lactate levels in weaning piglets. Meanwhile, T1 and T2 treatments significantly increased the positive rate of proliferating cell nuclear antigen (PCNA) of the small intestine, promoting intestinal cell proliferation. We also found that supplementation with glu, gln, and asp improved the serum amino acid pool and promoted ileal amino acid transporter gene expression of slc3a2, slc6a14, and slc7a11 in weaned piglets. Additionally, on day 21 post-weaning, T1 and T2 treatments stimulated the phosphorylation of the mTOR-S6K1-4EBP1 signaling pathway in the small intestine, which may implicate the enhanced protein synthesis rate. In summary, dietary supplementation of gln, glu, and asp was beneficial to the intestinal barrier function and amino acid pool regulation, while the benefits of gln, glu, and asp treatment might be diminished by the low-energy diet. The results demonstrated that the supplementation of gln, glu, and asp under low energy levels was preferentially supplied as the energy fuel to restore the gut barrier function in piglets on day 5 post-weaning. With the increase in age and intestinal maturation (on day 21 post-weaning), gln, glu, and asp supplementation could also show an effect on the regulation of the amino acid pool and protein synthesis.

Quantitative proteomics analysis revealed the potential role of lncRNA Ftx in cardiomyocytes.

OBJECTIVE: This study aims to decode the proteomic signature of cardiomyocytes in response to lncRNA Ftx knockdown and overexpression via proteomic analysis, and to study the biological role of lncRNA Ftx in cardiomyocytes.  METHODS: The expression level of the lncRNA Ftx in cardiomyocytes cultured in vitro was intervened, and the changes in protein levels in cardiomyocytes were quantitatively detected by liquid chromatography-mass spectrometry. The key molecules and pathways of the lncRNA-Ftx response were further examined by GO, KEGG, and protein interaction analysis. RESULTS: A total of 2828 proteins are quantified. With a 1.5-fold change threshold, 32 upregulated proteins and 49 downregulated proteins are identified in the lncRNA Ftx overexpression group, while 67 up-regulated proteins and 54 down-regulated proteins are identified in the lncRNA Ftx knockdown group. Functional clustering analysis of differential genes revealed that the lncRNA Ftx is involved in regulating cardiomyocyte apoptosis and ferroptosis and improving cellular energy metabolism. In addition, Hub genes such as ITGB1, HMGA2, STAT3, GSS, and LPCAT3 are regulated downstream by lncRNA Ftx. CONCLUSION: This study demonstrates that lncRNA Ftx plays a vital role in cardiomyocytes and may be involved in the occurrence and development of various myocardial diseases. It provides a potential target for clinical protection of the myocardium and reversal of myocardial fibrosis.

Analysis of transcriptome differences between subcutaneous and intramuscular adipose tissue of Ningxiang pigs.

To compare and analyze the molecular mechanisms of adipose deposition in subcutaneous fat (SAF)and intramuscular fat (IMF) tissues in Ningxiang pigs, differential gene expression profiles in SAF and IMF tissues of Ningxiang pigs were identified and analysed using RNA-seq technology. Six healthy 250-day-old male Ningxiang pigs with similar body weights (approximately 85 kg) of intraspecific individuals were selected as experimental material and samples of SAF and IMF tissues were collected. Differential genes associated with fat deposition and lipid metabolism were obtained by sequencing two adipose tissue transcriptomes and performing GO (Gene Ontology) functional annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. To verify the reliability of the sequencing results, six differential genes were randomly selected to validate using qRT-PCR. The results showed that we identified 2406 DEGs, with 1422 up-regulated and 984 down-regulated genes in two tissues. GO functional annotation analysis revealed that the differentially expressed genes were mainly involved in lipid metabolism related pathways, such as steroid biosynthesis, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and autophagy pathway. KEGG pathway enrichment showed that the differentially expressed genes were mainly enriched in the biological processes related to lipid binding, fatty acid metabolism, glycol ester metabolism, lipid biosynthesis and other biological processes related to lipid metabolism. Genes related to lipid metabolism, such as TCAP, NR4A1, ACACA, LPL, ELOVL6, DGAT1, PRKAA1, ATG101, TP53INP2, FDFT1, ACOX1 and SCD were identified by bioinformatic analyses and verified by qRT-PCR. Our results indicated that these genes may play important roles in the regulation of fat deposition and metabolism in the SAF and IMF tissue, providing the further mechanistic investigation of fat deposition in Ningxiang pigs.

Sex differences in factors associated with neck pain among undergraduate healthcare students: a cross-sectional survey.

BACKGROUND: Neck pain is widespread among students in healthcare-related fields. Although neck pain is more prevalent in females, since most research involves mixed-sex samples we know very little about sex differences in contributors to neck pain. Thus, this study sought to explore sex differences in the risk factors for neck pain in this high-risk population. METHODS: This cross-sectional study was conducted in China in 2021 and included a sample of 1921 undergraduate healthcare students (693 males, 1228 females) from 7 health professional schools at Fujian Medical University. We collected data on neck pain symptoms, demographics, behavioral and psychological factors. Multiple regression analysis was conducted to examine sex differences in the risk factors of neck pain. RESULTS: The overall prevalence of neck pain was 41.6% with female students having a higher prevalence than male students (44.4% vs. 36.7%, respectively). The adjusted analyses showed that self-study time ≥ 6 h/day (OR = 1.44, 95% CI:1.13-1.83), flexed neck posture >20 degrees (OR = 2.19, 95% CI: 1.28-3.74), static duration posture >2 h (OR = 1.42, 95% CI: 1.02-1.97), and psychological distress (high: OR = 2.04, 95% CI:1.42-2.94; very high: OR = 2.50, 95% CI:1.57-3.74; respectively) were independent factors for neck pain in females. Among males, self-study time ≥ 6 h/day (OR = 1.43, 95% CI: 1.02-2.01) and psychological distress (moderate: OR = 2.04, 95% CI:1.28-3.25; high: OR = 2.37, 95% CI:1.49-3.79; very high: OR = 2.97, 95% CI:1.75-5.02; respectively) were significant risk factors for neck pain. CONCLUSIONS: These findings suggest that the risk profiles of neck pain differ between females and males. The modifiable risk factors for neck pain, such as prolonged self-study time and elevated psychological distress, as well as poor posture among females, could be targeted through health promotion interventions in university settings.

Effects of Fermented Radix puerariae Residue on Nutrient Digestibility and Reproductive Performance of Sows.

This study was conducted to investigate the effect of fermented Radix puerariae residue (FRPR) on reproductive performance, apparent total tract digestibility (ATTD) of nutrients, and fecal short-chain fatty acid (SCFA) contents of sows. A total of 36 landrace × large white multiparous sows were randomly arranged into three treatments, representing supplementation with 0, 2, and 4% FRPR to a corn-soybean meal and wheat bran-based diet during the whole gestation period. The results showed that dietary FRPR had no effects on litter size and the number of total alive piglets (P > 0.05), and that the number of weaned piglets and weaning weight of litter were increased in sows with 4% FRPR treatment compared with control treatment (P < 0.05). Dietary 4% FRPR significantly decreased constipation rate, improved the ATTD of dry matter and organics, and fecal contents of acetate, propionate, and total SCFAs (P < 0.05). In the offspring piglets, serum concentrations of total protein, alkaline phosphatase, IgG, IL-10, and TGF-ß were increased, but blood urea nitrogen content was decreased with 4% FRPR treatment (P < 0.05). There were no significant differences in all determined indexes except for fecal acetic acid and total SCFAs between control and 2% FRPR treatment (P > 0.05). These findings indicated that FRPR used in the diets of sows showed positive effects on fecal characteristics, utilization of nutrients, and reproductive performance. Maternal supplementation with 4% FRPR is recommended for improving immune responses, weaning litter size, and litter weight of offspring piglets, which provide useful information for the application of residues of R. puerariae.

Serum Levels of HDL Cholesterol are Associated with Diffuse Axonal Injury in Patients with Traumatic Brain Injury.

BACKGROUND: It is well known that lipids are vital for axonal myelin repair. Diffuse axonal injury (DAI) is characterized by widespread axonal injury. The association between serum lipids and DAI is not well known. The purpose of this study was to investigate the associations of serum lipid profile variables (triglycerides, high- and low-density lipoproteins, and total cholesterol) with DAI detected by magnetic resonance imaging (MRI) and with clinical outcome for patients suffering from traumatic brain injury (TBI). METHODS: This study included 176 patients with a history of TBI who had undergone initial serum lipid measurements within 1 week and brain MRIs within 30 days. Based on MRI findings, patients were divided into negative and positive DAI groups. RESULTS: Of the 176 patients, 70 (39.8%) were assigned to DAI group and 106 (60.2%) patients to non-DAI group. Compared with the non-DAI group, patients with DAI had significantly lower levels of high-density lipoprotein cholesterol (HDL-C) in serum during the first week following TBI. Multivariate analysis identified HDL-C as an independent predictor of DAI. Patients with lower serum HDL-C levels were less likely to regain consciousness within 6 months in TBI patients with DAI lesions identified by MRI. CONCLUSIONS: Plasma levels of HDL-C may be a viable addition to biomarker panels for predicting the presence and prognosis of DAI on subsequent MRI following TBI.

Regulatory role of l-proline in fetal pig growth and intestinal epithelial cell proliferation.

l-proline (Pro) is a precursor of ornithine, which is converted into polyamines via ornithine decarboxylase (ODC). Polyamines plays a key role in the proliferation of intestinal epithelial cells. The study investigated the effect of Pro on polyamine metabolism and cell proliferation on porcine enterocytes in vivo and in vitro. Twenty-four Huanjiang mini-pigs were randomly assigned into 1 of 3 groups and fed a basal diet that contained 0.77% alanine (Ala, iso-nitrogenous control), 1% Pro or 1% Pro + 0.0167% α-difluoromethylornithine (DFMO) from d 15 to 70 of gestation. The fetal body weight and number of fetuses per litter were determined, and the small and large intestines were obtained on d 70 ± 1.78 of gestation. The in vitro study was performed in intestinal porcine epithelial (IPEC-J2) cells cultured in Dulbecco's modified Eagle medium-high glucose (DMEM-H) containing 0 µmol/L Pro, 400 µmol/L Pro, or 400 µmol/L Pro + 10 mmol/L DFMO for 4 d. The results showed that maternal dietary supplementation with 1% Pro increased fetal weight; the protein and DNA concentrations of the fetal small intestine; and mRNA levels for potassium voltage-gated channel, shaker-related subfamily, member 1 (Kv1.1) in the fetal small and large intestines (P < 0.05). Supplementing Pro to either gilts or IPEC-J2 cells increased ODC protein abundances and polyamine concentrations in the fetal intestines and IPEC-J2 cells (P < 0.05). In comparison with the Pro group, the combined administration of Pro and DFMO reduced the expression of ODC protein and spermine concentration in the fetal intestine, as well as the concentrations of putrescine, spermidine and spermine in IPEC-J2 cells (P < 0.05). Meanwhile, the percentage of cells in the S-phase and the mRNA levels of proto-oncogenes c-fos and c-myc were increased in response to Pro supplementation, whereas depletion of cellular polyamines with DFMO increased tumor protein p53 (p53) mRNA levels (P < 0.05). Taken together, dietary supplementation with Pro improved fetal pig growth and intestinal epithelial cell proliferation via enhancing polyamine synthesis.

Dietary glutamine, glutamate, and aspartate supplementation improves hepatic lipid metabolism in post-weaning piglets.

A previous study has demonstrated that early weaning significantly suppressed hepatic glucose metabolism in piglets. Glutamate (Glu), aspartate (Asp) and glutamine (Gln) are major metabolic fuels for the small intestine and can alleviate weaning stress, and therefore might improve hepatic energy metabolism. The objective of this study was to investigate the effects of administration of Glu, Asp and Gln on the expression of hepatic genes and proteins involved in lipid metabolism in post-weaning piglets. Thirty-six weaned piglets were assigned to the following treatments: control diet (Control; basal diet + 15.90 g/kg alanine); Asp, Gln and Glu-supplemented diet (Control + AA; basal diet + 1.00 g/kg Asp + 5.00 g/kg Glu + 10.00 g/kg Gln); and the energy-restricted diet supplemented with Asp, Gln and Glu (Energy- + AA; energy deficient diet + 1.00 g/kg Asp + 5.00 g/kg Glu + 10.00 g/kg Gln). Liver samples were obtained on d 5 and 21 post-weaning. Piglets fed Energy- + AA diet had higher liver mRNA abundances of acyl-CoA oxidase 1 (ACOX1), succinate dehydrogenase (SDH), mitochondrial transcription factor A (TFAM) and sirtuin 1 (SIRT1), as well as higher protein expression of serine/threonine protein kinase 11 (LKB1), phosphor-acetyl-CoA carboxylase (P-ACC) and SIRT1 compared with piglets fed control diet (P < 0.05) on d 5 post-weaning. Control + AA diet increased liver malic enzyme 1 (ME1) and SIRT1 mRNA levels, as well as protein expression of LKB1 and P-ACC on d 5 post-weaning (P < 0.05). On d 21 post-weaning, compared to control group, Glu, Gln and Asp supplementation up-regulated the mRNA levels of ACOX1, ME1 and SIRT1 (P < 0.05). These findings indicated that dietary Glu, Gln and Asp supplementation could improve hepatic lipid metabolism to some extent, which may provide nutritional intervention for the insufficient energy intake after weaning in piglets.

Dynamic changes in circulating levels of metabolites in the portal-drained viscera of finishing pigs receiving acute administration of l-arginine.

In this study, we examined the effects of acute intravenous administration of l-arginine on circulating levels of metabolites in the portal-drained viscera (PDV) of 12 barrows surgically fitted with chronic catheters in the portal vein. At day 14 post-surgery, the pigs were fasted for 12 hr and then randomly allocated to one of three groups to receive administration of normal saline, l-alanine [103 mg/kg body weight (BW), isonitrogenous control] or l-arginine-HCl (61 mg/kg BW), via the portal vein. Blood samples were obtained from the carotid artery before and at 30-min intervals for 5 hr after the administration of saline or amino acid in order to determine metabolic profiles. The results showed that, compared with the saline treatment, arginine infusion increased plasma concentrations of insulin-like growth factor-I, arginine and cystine in the portal vein plasma, whereas plasma concentrations of threonine, serine, leucine and methionine were reduced. These findings indicate that increasing arginine concentrations in the portal vein alters the metabolic profile in swine, an established animal model for studying human nutrition and metabolism.

Amino acids regulate energy utilization through mammalian target of rapamycin complex 1 and adenosine monophosphate activated protein kinase pathway in porcine enterocytes.

As major fuels for the small intestinal mucosa, dietary amino acids (AA) are catabolized in the mitochondria and serve as sources of energy production. The present study was conducted to investigate AA metabolism that supply cell energy and the underlying signaling pathways in porcine enterocytes. Intestinal porcine epithelial cells (IPEC-J2) were treated with different concentrations of AA, inhibitor, or agonist of mammalian target of rapamycin complex 1 (mTORC1) and adenosine monophosphate activated protein kinase (AMPK), and mitochondrial respiration was monitored. The results showed that AA treatments resulted in enhanced mitochondrial respiration, increased intracellular content of pyruvic acid and lactic acid, and increased hormone-sensitive lipase mRNA expression. Meanwhile, decreased citrate synthase, isocitrate dehydrogenase alpha, and carnitine palmitoyltransferase 1 mRNA expression were also observed. We found that AA treatments increased the protein levels of phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated-p70 ribosomal protein S6 kinase, and phosphorylated-4E-binding protein 1. What is more, the protein levels of phosphorylated AMPK α (p-AMPKα) and nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-1 (SIRT1) were decreased by AA treatments in a time depending manner. Mitochondrial bioenergetics and the production of tricarboxylic acid cycle intermediates were decreased upon inhibition of mTORC1 or AMPK. Moreover, AMPK activation could up-regulate the mRNA expressions of inhibitor of nuclear factor kappa-B kinase subunit beta (Ikbkß), integrin-linked protein kinase (ILK), unconventional myosin-Ic (Myo1c), ribosomal protein S6 kinase beta-2 (RPS6Kß2), and vascular endothelial growth factor (VEGF)-ß, which are downstream effectors of mammalian target of rapamycin (mTOR). The mRNA expressions of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD) and 5'-AMP-activated protein kinase subunit gamma-1 (PRKAG1), which are upstream regulators of mTOR, were also up-regulated by AMPK activation. On the other hand, AMPK activation also down-regulated FK506-binding protein 1A (FKBP1A), serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform, phosphatase and tensin homolog (PTEN), and unc-51 like autophagy activating kinase 1 (Ulk1), which are up-stream regulators of mTORC1. Taken together, these data indicated that AA regulated cellular energy metabolism through mTOR and AMPK pathway in porcine enterocytes. These results demonstrated interactions of AMPK and mTORC1 pathways in AA catabolism and energy metabolism in intestinal mucosa cells of piglets, and also provided reference for using AA to remedy human intestinal diseases.

Calycosin Influences the Metabolism of Five Probe Drugs in Rats.

BACKGROUND: Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb Astralagusmembranaceus (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases. AIM: The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism. METHODS: Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: No significant differences were observed for omeprazole and midazolam, compared to the control group. T max and t1/2 values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group (T max h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). C max of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, P<0.001). CONCLUSION: Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.

Role of Kelch-like ECH-associated Protein-1-Nuclear Factor Erythroid 2-related Factor-2/Antioxidant Responsive Element Signal Pathway for Multiple Sclerosis (review) / 中国康复理论与实践

Multiple sclerosis (MS) is a chronic inflammatory disease, mainly due to the activation of the T cells, which makes oxidative stress reaction in brain and leads to demyelination finally. Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor-2 (Nrf2)/antioxidant responsive element (ARE) signal pathway is one of the most important endogenous antioxidant pathways, which promotes the expression of detoxification enzymes and antioxidant protein to eliminate oxygen free radicals and balance intracellular redox system. Activation of the Keap1-Nrf2/ARE may delay the progression of MS by drugs or rehabilitation.

[Meta-analysis and trial sequential analysis of modified Sangbaipi Decoction for treating acute exacerbation of chronic obstructive pulmonary disease].

The randomized controlled trials about modified Sangbaipi Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) patients were collected from 7 databases( PubMed,CNKI,et al) from the establishment to December 5,2018. All the studies searched were strictly evaluated. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. To systematically review the efficacy of modified Sangbaipi Decoction in treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 25 RCTs involving 1 784 patients were included. According to the results of Meta-analysis,compared with the control groups,the trial group had a higher clinical efficacy in AECOPD patients( RR =1. 18,95%CI[1. 13,1. 22],P = 0),improved pulmonary functions including forced expiratory volume in one second( FEV1,WMD =0. 44,95%CI[0. 01,0. 87],P = 0. 046),and the forced vital capacity( FVC,WMD = 0. 42,95%CI[0. 07,0. 22],P = 0),but no statistical significance in the percentage of forced expiratory volume in one second( FEV1%,P = 0. 067) and the first seconds breathing volume percentage of forced vital capacity( FEV1/FVC,P = 0. 238); it improved the arterial oxygen partial pressure( PaO2,SMD =0. 85,95%CI[0. 41,1. 30],P = 0) and decreased the arterial partial pressure of carbon dioxide( PaCO2,SMD =-0. 94,95% CI[-1. 70,-0. 18],P= 0. 016); and in terms of inflammatory markers,it improved the white blood cell count( WBC,WMD=-0. 94,95%CI[-1. 17,-0. 70],P = 0). The trial sequential analysis showed that the studies included with the improvement of clinical efficacy had passed the conventional and TSA threshold,so as to further confirm the evidence. According to the findings,in addition to conventional Western medicine treatment,modified Sangbaipi Decoction could improve the efficiency in treating acute exacerbation patients with chronic obstructive pulmonary disease,increase PaO2,and decrease PaCO2,with a high safety but no effect on pulmonary function. However,restricted by the low quality of studies included,this conclusion shall be further verified by more high-quality clinical trials.