Differently Processed Low Doses of β-Glucan from Oat Bran Similarly Attenuate Postprandial Glycemic Response.

Incorporating β-glucan-rich oat bran (OB) can attenuate postprandial glycemic response (PPGR) in solid foods, but its effect in liquid matrices is unclear. This study investigated the ability of differently processed low-dose-β-glucan-containing beverages to lower PPGR, and the mechanisms of action. Twenty participants consumed five malt beverages made from cocoa powder: intact OB (Intact), OB treated with enzymatic hydrolysis (EnzymA, EnzymB) or extrusion (Extr), or no OB (Ctrl).

The bile acid chenodeoxycholic acid associates with reduced stroke in humans and mice.

Bile acids are liver-derived signaling molecules that can be found in the brain, but their role there remains largely unknown. We found increased brain chenodeoxycholic acid (CDCA) in mice with absent 12α-hydroxylase (Cyp8b1), a bile acid synthesis enzyme. In these Cyp8b1, and in Wt mice administered CDCA, stroke infarct area was reduced.

Rejuvenation of aged oocyte through exposure to young follicular microenvironment.

Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and developmental potential. A possible cause is aging of the surrounding follicular somatic cells that support oocyte growth and development by providing nutrients and regulatory factors. Here, by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed, we show that young oocytes cultured in aged follicles exhibited impeded meiotic maturation and developmental potential, whereas aged oocytes cultured within young follicles were significantly improved in rates of maturation, blastocyst formation and live birth after in vitro fertilization and embryo implantation.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

Background: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition.

Laboratory Scale Production of Complex Proteins Using Charge Complimentary Nanoenvironments.

Protein refolding is a crucial procedure in bacterial recombinant expression. Aggregation and misfolding are the two challenges that can affect the overall yield and specific activity of the folded proteins. We demonstrated the in vitro use of nanoscale "thermostable exoshells" (tES) to encapsulate, fold and release diverse protein substrates.

Chronometabolism: The Timing of the Consumption of Meals Has a Greater Influence Than Glycemic Index (GI) on the Postprandial Metabolome.

Eating late in the day is associated with circadian desynchrony, resulting in dysregulated metabolism and increased cardiometabolic disease risk. However, the underlying mechanisms remain unclear. Using targeted metabolomics of postprandial plasma samples from a secondary analysis of a randomised 2 × 2 crossover study in 36 healthy older Chinese adults, we have compared postprandial metabolic responses between high (HI) glycemic index (GI) or low-GI (LO) meals, consumed either at breakfast (BR) or at dinner (DI).

Novel Oxidative Stress Biomarkers with Risk Prognosis Values in Heart Failure.

Oxidative stress (OS) is mediated by reactive oxygen species (ROS), which in cardiovascular and other disease states, damage DNA, lipids, proteins, other cellular and extra-cellular components. OS is both initiated by, and triggers inflammation, cardiomyocyte apoptosis, matrix remodeling, myocardial fibrosis, and neurohumoral activation. These have been linked to the development of heart failure (HF).

Haploinsufficiency of CYP8B1 associates with increased insulin sensitivity in humans.

BACKGROUNDCytochrome P450 family 8 subfamily B member 1 (CYP8B1) generates 12α-hydroxylated bile acids (BAs) that are associated with insulin resistance in humans.METHODSTo determine whether reduced CYP8B1 activity improves insulin sensitivity, we sequenced CYP8B1 in individuals without diabetes and identified carriers of complete loss-of-function (CLOF) mutations utilizing functional assays.RESULTSMutation carriers had lower plasma 12α-hydroxylated/non-12α-hydroxylated BA and cholic acid (CA)/chenodeoxycholic acid (CDCA) ratios compared with age-, sex-, and BMI-matched controls.

Gastrointestinal Tract Stabilized Protein Delivery Using Disulfide Thermostable Exoshell System.

Thermostable exoshells (tES) are engineered proteinaceous nanoparticles used for the rapid encapsulation of therapeutic proteins/enzymes, whereby the nanoplatform protects the payload from proteases and other denaturants. Given the significance of oral delivery as the preferred model for drug administration, we structurally improved the stability of tES through multiple inter-subunit disulfide linkages that were initially absent in the parent molecule. The disulfide-linked tES, as compared to tES, significantly stabilized the activity of encapsulated horseradish peroxidase (HRP) at acidic pH and against the primary human digestive enzymes, pepsin, and trypsin.

Distinct transcriptomic and metabolomic profiles characterize NSAID-induced urticaria/angioedema patients undergoing aspirin desensitization.

Background: There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA).

Objectives: We sought to characterize the transcriptomic and metabolomic profiles of patients with NIUA undergoing aspirin desensitization.

Methods: PBMCs and plasma were separated from the blood of patients with NIUA undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls.

Bioorthogonal Catalysis for Treatment of Solid Tumors Using Thermostable, Self-Assembling, Single Enzyme Nanoparticles and Natural Product Conversion with Indole-3-acetic Acid.

Bioorthogonal catalysis (BC) generates chemical reactions not present in normal physiology for the purpose of disease treatment. Because BC catalytically produces the desired therapy only at the site of disease, it holds the promise of site-specific treatment with little or no systemic exposure or side effects. Transition metals are typically used as catalytic centers in BC; however, solubility and substrate specificity typically necessitate a coordinating enzyme and/or stabilizing superstructure for application.

Nanoencapsulation as a General Solution for Lyophilization of Labile Substrates.

Protein macromolecules occur naturally at the nanoscale. The use of a dedicated nanoparticle as a lyophilization excipient, however, has not been reported. Because biopolymeric and lipid nanoparticles often denature protein macromolecules and commonly lack the structural rigidity to survive the freeze-drying process, we hypothesized that surrounding an individual protein substrate with a nanoscale, thermostable exoshell (tES) would prevent aggregation and protect the substrate from denaturation during freezing, sublimation, and storage.

A general approach to protein folding using thermostable exoshells.

In vitro protein folding is a complex process which often results in protein aggregation, low yields and low specific activity. Here we report the use of nanoscale exoshells (tES) to provide complementary nanoenvironments for the folding and release of 12 highly diverse protein substrates ranging from small protein toxins to human albumin, a dimeric protein (alkaline phosphatase), a trimeric ion channel (Omp2a) and the tetrameric tumor suppressor, p53. These proteins represent a unique diversity in size, volume, disulfide linkages, isoelectric point and multi versus monomeric nature of their functional units.

Redefining IL11 as a regeneration-limiting hepatotoxin and therapeutic target in acetaminophen-induced liver injury.

Acetaminophen (-acetyl--aminophenol; APAP) toxicity is a common cause of liver damage. In the mouse model of APAP-induced liver injury (AILI), interleukin 11 (IL11) is highly up-regulated and administration of recombinant human IL11 (rhIL11) has been shown to be protective. Here, we demonstrate that the beneficial effect of rhIL11 in the mouse model of AILI is due to its inhibition of endogenous mouse IL11 activity.

Robust Performance of Potentially Functional SNPs in Machine Learning Models for the Prediction of Atorvastatin-Induced Myalgia.

Statins can cause muscle symptoms resulting in poor adherence to therapy and increased cardiovascular risk. We hypothesize that combinations of potentially functional SNPs (pfSNPs), rather than individual SNPs, better predict myalgia in patients on atorvastatin. This study assesses the value of potentially functional single nucleotide polymorphisms (pfSNPs) and employs six machine learning algorithms to identify the combination of SNPs that best predict myalgia.

A metabolomic analysis of thiol response for standard and modified N-acetyl cysteine treatment regimens in patients with acetaminophen overdose.

N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose.

Prioritizing Candidates of Post-Myocardial Infarction Heart Failure Using Plasma Proteomics and Single-Cell Transcriptomics.

Background: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery.

Methods: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.

Predicting the Shapes of Protein Complexes through Collision Cross Section Measurements and Database Searches.

In structural biology, collision cross sections (CCSs) from ion mobility mass spectrometry (IM-MS) measurements are routinely compared to computationally or experimentally derived protein structures. Here, we investigate whether CCS data can inform about the shape of a protein in the absence of specific reference structures. Analysis of the proteins in the CCS database shows that protein complexes with low apparent densities are structurally more diverse than those with a high apparent density.

Magnetic fields modulate metabolism and gut microbiome in correlation with Pgc-1α expression: Follow-up to an in vitro magnetic mitohormetic study.

Exercise modulates metabolism and the gut microbiome. Brief exposure to low mT-range pulsing electromagnetic fields (PEMFs) was previously shown to accentuate in vitro myogenesis and mitochondriogenesis by activating a calcium-mitochondrial axis upstream of PGC-1α transcriptional upregulation, recapitulating a genetic response implicated in exercise-induced metabolic adaptations. We compared the effects of analogous PEMF exposure (1.

Patients with acute and chronic coronary syndromes have elevated long-term thrombin generation.

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Despite significant advances in revascularization strategies and antiplatelet therapy with aspirin and/or P2Y receptor antagonist, patients with acute coronary syndrome (ACS) continue to be at long-term risk of further cardiovascular events. Besides platelet activation, the role of thrombin generation (TG) in atherothrombotic complications is widely recognized.

Surface protein engineering increases the circulation time of a cell membrane-based nanotherapeutic.

Mammalian cell membranes are often incompatible with chemical modifications typically used to increase circulation half-life. Using cellular nanoghosts as a model, we show that proline-alanine-serine (PAS) peptide sequences expressed on the membrane surface can extend the circulation time of a cell membrane derived nanotherapeutic. Membrane expression of a PAS 40 repeat sequence decreased protein binding and resulted in a 90% decrease in macrophage uptake when compared with non-PASylated controls (P ≤ 0.

The Importance of Sex Stratification in Autoimmune Disease Biomarker Research: A Systematic Review.

The immune system is highly dynamic and regulated by many baseline characteristic factors. As such, significant variability may exist among different patient groups suffering from the same autoimmune disease (AD). However, contemporary research practices tend to take the reductionist aggregate approach: they do not segment AD patients before embarking on biomarker discovery.