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Food-derived bioactive peptides offer great potential for the treatment and maintenance of various health conditions, including chronic inflammation. Using in vitro testing in human macrophages, a rice derived functional ingredient natural peptide network (NPN) significantly reduced Tumour Necrosis Factor (TNF)-α secretion in response to lipopolysaccharides (LPS). Using artificial intelligence (AI) to characterize rice NPNs lead to the identification of seven potentially active peptides, the presence of which was confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Characterization of this network revealed the constituent peptides displayed anti-inflammatory properties as predicted in vitro. The rice NPN was then tested in an elderly “inflammaging” population with a view to subjectively assess symptoms of digestive discomfort through a questionnaire. While the primary subjective endpoint was not achieved, analysis of objectively measured physiological and physical secondary readouts showed clear significant benefits on the ability to carry out physical challenges such as a chair stand test that correlated with a decrease in blood circulating TNF-α. Importantly, the changes observed were without additional exercise or specific dietary alterations. Further health benefits were reported such as significant improvement in glucose control, a decrease in serum LDL concentration, and an increase in HDL concentration; however, this was compliance dependent. Here we provide in vitro and human efficacy data for a safe immunomodulatory functional ingredient characterized by AI.

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The prevalence of prediabetes is rapidly increasing, and this can lead to an increased risk for individuals to develop type 2 diabetes and associated diseases. Therefore, it is necessary to develop nutritional strategies to maintain healthy glucose levels and prevent glucose metabolism dysregulation in the general population. Functional ingredients offer great potential for the prevention of various health conditions, including blood glucose regulation, in a cost-effective manner. Using an artificial intelligence (AI) approach, a functional ingredient, NRT_N0G5IJ, was predicted and produced from Pisum sativum (pea) protein by hydrolysis and then validated. Treatment of human skeletal muscle cells with NRT_N0G5IJ significantly increased glucose uptake, indicating efficacy of this ingredient in vitro. When db/db diabetic mice were treated with NRT_N0G5IJ, we observed a significant reduction in glycated haemoglobin (HbA1c) levels and a concomitant benefit on fasting glucose. A pilot double-blinded, placebo controlled human trial in a population of healthy individuals with elevated HbA1c (5.6% to 6.4%) showed that HbA1c percentage was significantly reduced when NRT_N0G5IJ was supplemented in the diet over a 12-week period. Here, we provide evidence of an AI approach to discovery and demonstrate that a functional ingredient identified using this technology could be used as a supplement to maintain healthy glucose regulation.

It is well known that cardiopulmonary bypass (CPB) causes major hemodynamic and physiologic disturbances. These may be alleviated by replacing conventional nonpulsatile perfusion with pulsatile flow, which under normothermic conditions results in a lower peripheral vascular resistance, associated with lower plasma angiotensin II and vasopressin levels, t, 2 It is also known that release of the endogenous vasodilator nitric oxide (NO) is sensitive to flow pulsatility, 3' 4 a mechanism that may contribute to the improved peripheral hemodynamics associated with pulsatile perfusion. We therefore tested the hypothesis that higher NO activity is associated with pulsatile flow than with nonpulsatile flow during and immediately after normothermic CPB. We also investigated whether hypothermic CPB modulated any observed differences.Twenty-four patients without diabetes who were undergoing elective CPB (2.4 L-min -1. m -2) for coronary artery bypass grafting were randomly assigned to four groups: 37 ° C with pulsatile flow, 37 ° C with nonpulsatile flow, 28 ° C with pulsatile flow, and 28 ° C with nonpulsatile flow (n = 6 per group). There were no differences among the groups with respect to age (mean for 24 patients of 59.3 years), number of arteries grafted (median for all groups of 3), crossclamp time (mean for 24 patients of 33.9 minutes), or smoking habits. The same anesthetic regimen (methohexitone, fentanyl, midazolam, and enflurane) was employed for all subjects. Preoperative use of /3-blockers, calcium antagonists, oral nitrates, and aspirin did not differ among the groups; any nitrate medications were discontinued at least 12 hours before operation and were not recommenced until after our investigation. In each patient, arterial blood pressure, cardiac output (by thermal dilution), and gastric mucosal blood flow (by laser Doppler velocimetry) were measured, and peripheral vascular resistance was calculated. Sampling of peripheral venous blood for plasma nitrite plus nitrate (index of NO activity) was achieved at the following time points: 45 minutes after induction of anesthesia (time point A, baseline); 10 minutes (B) and 20 minutes (C) after commencement of CPB; 10 minutes after release of the aortic crossclamp (D); and 10 minutes (E) and 30 minutes (F) after CPB was discontinued. Plasma nitrite plus

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Delayed local myocardial power development (primary asynchrony) has been suggested as a marker of ischaemic ventricular dysfunction in humans. However, to prove this, microcirculatory perfusion, microcirculatory oxygenation, and intrinsic mechanical function of the same asynchronous myocardial segment should be studied simultaneously before and after revascularisation. We performed a prospective intraoperative study of 15 patients (age 67 [SD 5] years) at baseline and 30 min after left anterior descending artery grafting. Local tissue perfusion and oxygenation of the anterior left ventricular wall were quantified with a voltammetric microelectrode technique. Transesophageal M-mode echocardiograms and simultaneous high-fidelity left ventricular pressure were measured. Eight patients showed primary asynchrony and 7 did not. Patients with primary asynchrony had local mechanical depression with lower resting values of myocardial work and peak power which increased with surgery. In this group, resting perfusion consistently increased with surgery (32.1 [13] to 54 [31] ml min(-1) 100 g(-1), P < 0.05). In the remaining patients, local work and power were normal, and resting perfusion was consistently higher (90 [9] Ml min(-1) 100 g(-1), P < 0.05 vs primary asynchrony), and fell with surgery. Local tissue oxygen tension was similar in both groups (38 vs 44 mmHg) and did not change with surgery. In patients with chronic coronary artery disease, microcirculatory perfusion, but not pO2, is reduced in regions showing primary asynchrony and impaired mechanical function. Abnormalities in both mechanical function and perfusion normalise within 30 min of revascularisation. These data provide further evidence that primary asynchrony is not only a marker of chronic ischemic ventricular dysfunction, but is associated with a modified contraction pattern in which normal oxygen tension coexists with reduced perfusion.