Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.

Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker.

A novel CD34-specific T-cell engager efficiently depletes acute myeloid leukemia and leukemic stem cells and .

Less than a third of patients with acute myeloid leukemia (AML) are cured by chemotherapy and/or hematopoietic stem cell transplantation, highlighting the need to develop more efficient drugs. The low efficacy of standard treatments is associated with inadequate depletion of CD34+ blasts and leukemic stem cells, the latter a drug-resistant subpopulation of leukemia cells characterized by the CD34+CD38- phenotype. To target these drug-resistant primitive leukemic cells better, we have designed a CD34/CD3 bi-specific T-cell engager (BTE) and characterized its anti-leukemia potential in vitro, ex vivo and in vivo.

Identification of Endothelial Proteins in Plasma Associated With Cardiovascular Risk Factors.

Objective: Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor treatment response.

Implication of Opioid Receptors in the Antihypertensive Effect of a Bovine Casein Hydrolysate and α-Casein-Derived Peptides.

The antihypertensive activity of two α-casein-derived peptides and casein hydrolysate containing these sequences was evaluated in the presence of naloxone. The activity was abolished by this opioid antagonist at 2, 4, and 6 h post-administration. Similarly, the antihypertensive effect of the α-casein peptides RYLGY (-23.

Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage.

Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma.

PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study.

There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish "Venous Thromboembolism Biomarker Study," using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins.

Role of intestinal brush border peptidases in the simulated digestion of milk proteins.

Scope: This study aimed to assess the impact of the "often neglected" intestinal brush border membranes (BBMs) hydrolases on dietary peptides, exploring the possibility that the disintegration of proteins progressed in the small intestine up to a "core" of intrinsically stable oligopeptides, persisting independently on the up-stream breakdown.

Methods And Results: Samples of sodium caseinate, skim milk powder, and whey protein isolate were submitted to in vitro simulated gastropancreatic digestion using two different procedures: (i) a simplified model involving the main compartmental specific proteases; (ii) a static digestion method based on a frameset of parameters inferred from in vivo. The gastroduodenal digesta were further hydrolyzed with peptidases from porcine jejunal BBM.

Bioavailability and kinetics of the antihypertensive casein-derived peptide HLPLP in rats.

The aim of this study was to investigate the oral bioavailability and kinetics of the milk casein-derived peptide HLPLP, which had previously demonstrated antihypertensive effect in spontaneously hypertensive rats. HLPLP disposition after single intravenous (4 mg/kg body weight) and oral (40 mg/kg body weight) doses was studied in rats. Plasma concentrations of HLPLP [β-casein fragment f(134-138)], and two derived fragments found after HLPLP administration, LPLP [β-casein fragment f(135-138)] and HLPL [β-casein fragment f(134-137)], were determined by ultrahigh performance liquid chromatography (UPLC) coupled on line to a Q-TOF instrument.

Peptidomic study of Spanish blue cheese (Valdeón) and changes after simulated gastrointestinal digestion.

It is increasingly evident that digestion can affect the biological activity of cheese by the release of new active peptides from their precursors or, on the contrary, giving rise to fragments without activity. The characterization of the peptidome of a Spanish blue cheese, Valdeón, has been conducted before and after gastrointestinal digestion, and the digests have been compared to those obtained from pasteurized skimmed milk powder (SMP) using a bioinformatics platform. Peptidomic profiling of digests revealed several regions that are especially resistant to digestion (among them β-casein 60-93, 128-140, and 193-209).

Novel antihypertensive lactoferrin-derived peptides produced by Kluyveromyces marxianus: gastrointestinal stability profile and in vivo angiotensin I-converting enzyme (ACE) inhibition.

Novel antihypertensive peptides released by Kluyveromyces marxianus from bovine lactoferrin (LF) have been identified. K. marxianus LF permeate was fractionated by semipreparative high performance liquid chromatography and 35 peptides contained in the angiotensin I-converting enzyme (ACE)-inhibitory fractions were identified by using an ion trap mass spectrometer.

Short communication: peptide profiling in cheeses packed using different technologies.

Peptides released during the shelf life of cheeses packaged using 2 different technologies, vacuum packaging (VP) and modified-atmosphere packaging (MAP), were identified by on-line reverse phase-HPLC-tandem mass spectrometry. A total of 22 peptides from the N-terminal domain of αS1-casein (CN) and 26 from β-CN were identified, the latter more evenly distributed over the whole sequence. Peptides were monitored during the shelf life of these cheeses when stored at 4°C, revealing that the peptide profile changed significantly with the storage time.