Effects of Compound Probiotics on Cecal Microbiome and Metabolome of Shaoxing Duck

This experiment was conducted to investigate the effects of compound probiotics on intestinal microflora and metabolome of Shaoxing ducks. A total of 640 1-day-old Shaoxing ducks were randomly divided into two treatments with eight replicates and forty ducks for each replicate. The ducks were fed basal diet (Ctrl) and basal diet supplemented with 0.15% compound probiotics (MixP). The experiment lasted for 85 days. The results showed that the abundance of Bacteroidetes and Bacteroides in MixP was higher than that in Ctrl (P < 0.05). However, the abundance of Firmicutes and Oscillospira and Desulfovibrio in MixP was lower than that in Ctrl (P < 0.05). Concentrations of 71 metabolites differed significantly (P < 0.05) between the MixP and the Ctrl groups; for example, Pyridoxal (Vitamin B6), L-Arginine, and Betaine aldehyde were up-regulated (P < 0.05), and 7-oxocholesterol, 3-hydroxy-L-kynureni-ne, and N-acetyl-d-glucosamine were down-regulated (P < 0.05). KEGG was enriched in 15 metabolic pathways. The pathways of Vitamin B6 metabolism, Vascular smooth muscle contraction, Vitamin digestion and absorption, and Protein digestion and absorption were influenced by compound probiotics supplementation. Thus, supplementation of compound probiotics improved cecal heath through shifts in the cecal microbiome and metabolome.

Dynamics and Functional Interplay of Non-histone Lysine Crotonylome and Ubiquitylome in Vascular Smooth Muscle Cell Phenotypic Remodeling

BackgroundsCrotonylation of histones is a recently discovered type of post-translational modification that can regulate gene expression. However, the function of crotonylation on nonhistone proteins in vascular smooth muscle cells (VSMC) is unclear. Here, we aim to use modification and proteomic analysis to find the cellular characteristic of crotonylated nonhistone proteins and the crosstalk with ubiquitinated proteins in vascular smooth muscle cell (VSMC) phenotypic remodeling. ResultsWe performed modification and proteomic analysis of VSMCs before and after platelet-derived growth factor-BB (PDGF-BB) stimulation. The crotonylated and ubiquitinated pan-antibody was used to enrich the protein and then subjected to high-throughput mass spectrometry analysis. Then we compared the enrichment analysis of differentially modified proteins in regards to GO terms, KEGG pathway and protein domain. As a result, there were 2138 crotonylation sites in 534 proteins and 1359 ubiquitination sites corresponding to 657 proteins. The crotonylated proteins participate in a variety of important cellular pathways and perform different functions in VSMCs. Among them, some proteins were found to be closely involved in the physiological process of VSMC phenotypic remodeling including glycolysis/gluconeogenesis, vascular smooth muscle contraction, and PI3K-Akt signaling pathway. Furthermore, the KEGG pathway enrichment analysis showed that the ubiquitinated proteins were found to be closely involved in the physiological process of VSMC phenotypic remodeling including glycolysis/gluconeogenesis, vascular smooth muscle contraction, RAS signaling pathway or PI3K-Akt signaling pathway. Crosstalk analysis showed that there were 199 sites within 177 proteins modified by crotonylation and ubiquitination simultaneously. PPI network analysis indicated that crotonylated and ubiquitinated proteins played an important role in cellular bioprocess commonly and possible synergistic effect. ConclusionsIn summary, our bioinformatics show that nonhistone crotonylation and ubiquitination play an important role in the VSMC phenotypic transformation induced by PDGF-BB stimulation. The crosstalk of crotonylation and ubiquitination in glycolysis is possibly a novel mechanism underlying the VSMC phenotypic remodeling.

Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

The α1-adrenergic receptors (ARs) are G-protein coupled receptors that bind the endogenous catecholamines, norepinephrine, and epinephrine. They play a key role in the regulation of the sympathetic nervous system along with β and α2-AR family members. While all of the adrenergic receptors bind with similar affinity to the catecholamines, they can regulate different physiologies and pathophysiologies in the body because they couple to different G-proteins and signal transduction pathways, commonly in opposition to one another. While α1-AR subtypes (α1A, α1B, α1C) have long been known to be primary regulators of vascular smooth muscle contraction, blood pressure, and cardiac hypertrophy, their role in neurotransmission, improving cognition, protecting the heart during ischemia and failure, and regulating whole body and organ metabolism are not well known and are more recent developments. These advancements have been made possible through the development of transgenic and knockout mouse models and more selective ligands to advance their research. Here, we will review the recent literature to provide new insights into these physiological functions and possible use as a therapeutic target.

Increased expression of HIST1H1D in esophageal carcinoma predicts poor survival: A study base on TCGA database

Background: Expression level of HIST1H1D, a linker histone H1 gene, was reported to be associated with poor prognosis in some malignant tumors. Online database showed that HIST1H1D was increased in esophageal carcinoma. The current study aimed to evaluated the role of HIST1H1D in esophageal carcinoma using online data from The Cancer Genome Atlas (TCGA).Methods. Wilcoxon signed-rank test, cox regression analysis and multivariant analysis were used to analyze the relationship between clinical characteristic and HIST1H1D expression level. Kaplan-Meier method was used to analyze the association of HIST1H1D and overall survival. Gene set enrichment analysis (GSEA) was used to identify HIST1H1D-related signaling pathway.Results. Compared to normal sample, HIST1H1D was significantly increased in esophageal carcinoma sample (p=0.000). High HIST1H1D expression was associated with poor survival (p=0.035). Univariate analysis showed that high HIST1H1D expression was associated with a poor overall survival (HR:1.19, 95% confidence interval [CI]: 1.05-1.34, p=0.01). Multivariate analysis indicated that HIST1H1D remained an independent prognostic predictor of overall survival (HR:1.18, 95% confidence interval [CI]: 1.02-1.36, p=0.03). GSEA revealed that alpha linolenic acid metabolism, arachidonic acid metabolism, histidine metabolism, vascular smooth muscle contraction, primary bile acid biosynthesis, phenylalanine metabolism and ether lipid metabolism were enriched in HIST1H1D high expression phenotype.Conclusions: HIST1H1D may sever as a potential prognostic predictor of poor survival in esophageal carcinoma. Lipid metabolism, histidine metabolism, vascular smooth muscle contraction, primary bile acid biosynthesis, phenylalanine metabolism and ether lipid metabolism may be the key signaling pathway regulated by HIST1H1D.

Do Mistletoe (Viscum album L.) Lectins Influence Isometric Contraction of Non-diseased Human Mesenteric Arteries ex vivo?

Mistletoe (Viscum album L., VA) lectins (MLs) are plant lectins with potent anticancer activity. Although wide use of VA extracts in curing cancer, the effects of purified MLs on human vasculature in term of possible side effect of the lectin has not yet been reported. The present study was aimed to investigate isometric contractions of isolated human mesenteric arteries during MLs application. The contractile response of arteries was studied using Mulvany-Halpern myograph and the isometric contractions under MLs’ treatment were examined in artery segments with either intact endothelium or after endothelium removal. Furthermore, the effect of the lectin was assessed in arterial preparations in basal tension, in arteries precontracted with 42 mM KCl as a depolarizing stimulus or endothelin-1 (ET-1) as a potent receptor-operated agonist of vascular smooth muscle contraction. The results showed that MLs (1 to 100 nM) failed to affect the high K+-induced contractions of both endothelium-intact and endothelium-denuded arteries. The contractions of tissue preparations without endothelium in basal tone or after ET-1 (1 nM) treatment were also not affected by the application of MLs. The observed mild effect of MLs on the contractility of human vasculature may potentially be beneficial with MLs-based anticancer therapy without vascular side effects.

Acute glucose influx-induced mitochondrial hyperpolarization inactivates myosin phosphatase as a novel mechanism of vascular smooth muscle contraction

It is well-established that long-term exposure of the vasculature to metabolic disturbances leads to abnormal vascular tone, while the physiological regulation of vascular tone upon acute metabolic challenge remains unknown. Here, we found that acute glucose challenge induced transient increases in blood pressure and vascular constriction in humans and mice. Ex vivo study in isolated thoracic aortas from mice showed that glucose-induced vascular constriction is dependent on glucose oxidation in vascular smooth muscle cells. Specifically, mitochondrial membrane potential (ΔΨm), an essential component in glucose oxidation, was increased along with glucose influx and positively regulated vascular smooth muscle tone. Mechanistically, mitochondrial hyperpolarization inhibited the activity of myosin light chain phosphatase (MLCP) in a Ca2+-independent manner through activation of Rho-associated kinase, leading to cell contraction. However, ΔΨm regulated smooth muscle tone independently of the small G protein RhoA, a major regulator of Rho-associated kinase signaling. Furthermore, myosin phosphatase target subunit 1 (MYPT1) was found to be a key molecule in mediating MLCP activity regulated by ΔΨm. ΔΨm positively phosphorylated MYPT1, and either knockdown or knockout of MYPT1 abolished the effects of glucose in stimulating smooth muscle contraction. In addition, smooth muscle-specific Mypt1 knockout mice displayed blunted response to glucose challenge in blood pressure and vascular constriction and impaired clearance rate of circulating metabolites. These results suggested that glucose influx stimulates vascular smooth muscle contraction via mitochondrial hyperpolarization-inactivated myosin phosphatase, which represents a novel mechanism underlying vascular constriction and circulating metabolite clearance.