The cientificWorldJOURNAL Clinical Study Whey Protein Lycosome Formulation Improves Vascular Functions and Plasma Lipids with Reduction of Markers of Inflammation and Oxidative Stress in Prehypertension

Parameters reflecting cardiovascular health and inflammation were studied in a pilot clinical trial conducted on 40 patients with prehypertension. The patients were treated with a new proprietary formulation of a whey protein (WP) isolate embedded into lycopene micelles (WPL) during a 1-month period. Control groups received lycopene or WP as a singular formulation or placebo pills for the same period of time. Combined WPL formulation of whey protein and lycopene has caused multiple favorable changes in the cardiovascular function (including a tendency to the reduced systemic blood pressure), the plasma lipid profile, and the inflammatory status of patients with prehypertension, whereas singular formulations of the compounds and placebo did not have such an effect. The reduction of plasma triglycerides and cholesterol fractions and almost two-fold decline in C-reactive protein (CRP) and inflammatory oxidative damage (IOD) levels as well as an increase in nitric oxide (NO), tissue oxygenation (StO 2 ), and flow-mediated dilation values constitute the most significant benefit/outcome of the treatment with the combined formulation of whey protein and lycopene. The treatment did not affect the values of ankle-brachial index (ABI), body weight, and body mass index (BMI)

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Whey Protein Lycosome Formulation Improves Vascular Functions and Plasma Lipids with Reduction of Markers of Inflammation and Oxidative Stress in Prehypertension

Parameters reflecting cardiovascular health and inflammation were studied in a pilot clinical trial conducted on 40 patients with prehypertension. The patients were treated with a new proprietary formulation of a whey protein (WP) isolate embedded into lycopene micelles (WPL) during a 1-month period. Control groups received lycopene or WP as a singular formulation or placebo pills for the same period of time. Combined WPL formulation of whey protein and lycopene has caused multiple favorable changes in the cardiovascular function (including a tendency to the reduced systemic blood pressure), the plasma lipid profile, and the inflammatory status of patients with prehypertension, whereas singular formulations of the compounds and placebo did not have such an effect. The reduction of plasma triglycerides and cholesterol fractions and almost two-fold decline in C-reactive protein (CRP) and inflammatory oxidative damage (IOD) levels as well as an increase in nitric oxide (NO), tissue oxygenation (StO2), and flow-mediated dilation values constitute the most significant benefit/outcome of the treatment with the combined formulation of whey protein and lycopene. The treatment did not affect the values of ankle-brachial index (ABI), body weight, and body mass index (BMI)

Reduction of elevated lipids and low‐density lipoprotein oxidation in serum of individuals with subclinical hypoxia and oxidative stress supplemented with lycosome formulation of docosahexaenoic acid

Thirty two individuals aged 40–65 years old with a moderate hyperlipidemia (serum triglycerides > 150 mg/dl and LDL from 130 to 160 mg/dl) were supplemented once daily for 30 days with a 250 mg conventional formulation of docosahexaenoic acid (DHA) without lycopene (CF‐DHA) or 250 mg of lycosome‐formulated DHA containing 7 mg of lycopene (LF‐DHA). It was shown that ingestion of CF‐DHA led to a transient increase in serum DHA level after 2 weeks of the trial, whereas LF‐DHA did not cause significant changes in serum DHA. However, there was a noticeable increase in serum eicosapentaenoic acid levels exceeding the pretreatment value by 42.8% and 39.1% after the 2nd and 4th weeks of LF‐DHA ingestion. Patients supplemented with LF‐DHA showed a significant (19.5 mg/dl, p < 0.05) decline in LDL, which was accompanied by a corresponding decrease in total serum cholesterol and a much stronger reduction in serum triglyceride levels (reduction of medians by 27.5 mg/dl). No changes in HDL were observed. LF‐DHA caused a significant decline in the serum level of malonic dialdehyde (MDA), whereas the components of LF‐DHA, lycopene and DHA, ingested as two separate formulations had a less significant effect on serum MDA. Moreover, LF‐DHA increased both the plasma oxygen transport and tissue oxygen saturation by the end of the observational period, while lycopene or DHA taken alone, or both of them co‐ingested separately had none or a much less effect on the oxygen turnover parameters

Ingestion of Lycosome L-tug Formulation of Dark Chocolate Ameliorates Postprandial Hyperlipidemia and Hyperglycemia in Healthy Volunteers

Twenty-eight healthy middle-aged volunteers (40-60 years old) with equal gender representation were randomized into 3 study groups to investigate the changes in postprandial glucose and lipids after ingestion of different formulations of dark chocolate (DC). The volunteers from the first group were requested to ingest 100 g of regular DC whereas the individuals from the third group were given 100 g of highly bioavailable lycosome formulated L-tug formulation of DC containing 23.3 mg of lycopene. A second group received a 23.3 mg lycopene capsule, a tomato-derived antioxidant carotenoid as a matching control. Serum specimens were obtained following 30 minutes as well as 1, 2, and 3 hours after study products intake. Ingestion of L-tug DC was accompanied by the reduced postprandial hyperglycemia with maximum difference seen at 3rd hour of the study and reduction of average AUCGluc values by 20% (P<0.05) as compared to regular DC. Moreover, ingestion of L-tug DC was accompanied by a statistically significantly reduced median concentration for postprandial triglycerides (to 390.7 mg⁎hr/dL; 5/95%% CIs: 363.2/405.7 versus regular DC value of 439.5mg⁎hr/dL and a lower range of confidence intervals - 5/95%CIs: 394.0/475.1). A similar tendency was observed in changes of total cholesterol concentration. Ingestion of L-tug DC completely abolished total cholesterol increase seen in volunteers at 3rd hour of postprandial period following intake of the control DC. Ingestion of lycopene alone did not cause any changes in postprandial changes of glucose or serum lipids. The observed postprandial changes can be related to the 56.2 % increase in serum lycopene level which was observed after ingestion of L-tug DC only. Higher serum lycopene levels following the ingestion of L-tug DC resulted in a corresponding increase in serum antioxidant capacity and reduction of oxidized LDL as well as a decline in malonic dialdehyde concentration in the serum of volunteers

Reduction of Liver Span and Parameters of Inflammation in Nonalcoholic Fatty Liver Disease Patients Treated with Lycosome Formulation of Phosphatidylcholine: A Preliminary Report

Twenty-nine newly diagnosed individuals with Nonalcoholic Fatty Liver Disease (NAFLD) remaining on habitual dietary regimen were supplemented with regular or lycosome formulations of phosphatidylcholine (PC) during a pilot, randomized, double-blinded clinical study. After two months of oral PC intake (450 mg daily) the liver size as well as serum levels of hepatic enzymes and markers of inflammation were evaluated by ultrasonography and biochemical analysis. It was shown that there was a statistically significant reduction of medians for the Mid-Clavicular liver size from 16.0 cm (95/5% CI: 17.1/15.5) to 15.1 cm (95/5% CI: 17.2/14.4, P=0.021) in participants ingesting the lycosome-formulated PC (L-PC) whereas regular formulation of PC (R-PC) had only a marginal effect on this parameter (P=0.044). A similar tendency was observed in the Mid-Sternal liver size. Moreover, there was a reduction of medians for ALT values at the end point of the study (P=0.026) after ingestion of L-PC, while R-PC had no statistically significant effect. On the other hand, ingestion of both formulations was accompanied by reductions in values for Inflammatory Oxidative Damage (IOD) and oxidized LDL in serum. However, L-PC had superior activity in these terms, presumably due to the presence of lycopene, a powerful antioxidant, in the L-PC-Lycosome structure. C-reactive protein level was moderately decreased (reduction of medians from 6.5 [95/5% CI: 7.7/5.8] mg/L to 5.1 [95/5% CI: 5.6/4.3] mg/L) only after ingestion of L-PC. The greater efficacy of L-PC seen in NAFLD volunteers may reflect improved bioavailability of PC owing to better protection of the microencapsulated PC from gastrointestinal enzymes and possibly enhanced hepatic delivery of L-PC particles

Effect of Lycosome-Formulated Phosphatidylcholine on Parameters of Biological Oxidation after Single Intake of Moderate Amount of Alcohol

Ingestion of a single dose of alcohol, ranging from the intake of a moderate amount alcohol to binge drinking, is the most frequent form of alcohol consumption with poorly understood medical consequences and obscure prophylactics. The study was aimed to determine whether lycosome formulated phosphatidylcholine (PC-Lyc) containing two highly bioavailable antioxidants (PC and lycopene) ingested shortly before the alcohol-containing beverage may alleviate the biochemical markers of liver damage and parameters of biological oxidation associated with the intake of a moderate amount of alcohol. Healthy middle-aged volunteers were requested to consume a moderate amount of alcohol – 0.5 ml/kg or 1.0 ml/kg shortly after ingestion of a capsule containing 450 mg of regular phosphatidylcholine (PC, n=10), PC-Lyc (n=10), or placebo pill (PP, n=10). Serum levels of ethanol (EtOH), acetaldehyde (AA), liver-specific enzymes, total antioxidant capacity of serum (TAC), oxidized LDL (LDL-Px), and malonic dialdehyde (MDA) were measured at 1, 2.5, and 5 hours after dosing with alcohol. Ingestion of PC regardless of the formulation used had no effect on serum EtOH concentration dynamics. However, volunteers supplemented with PC-Lyc showed a better clearance of AA in serum as compared to other groups. There was a reduction in serum TAC values by 18.5% and 16.1% in both placebo groups ingesting 0.5 and 1.0 ml/kg of alcohol, respectively, at the end of observational period. This decline was preventable by supplementation of volunteers with PC and especially with PC-Lyc. Moreover, PC-Lyc promoted a reduction of serum MDA and reversed an increase in serum LDL-Px. In addition, ingestion of alcohol at 1.0 ml/kg dose caused a transient increase in serum alanine-aminotransferase activity which was abolished by both formulations of PC. Therefore, combinatory lycosomal formulation of PC and lycopene may prevent some metabolic abnormalities associated with single intake of moderate amount of alcohol. This trial is registered with ACTRN12617001335381

Effect of lycopene supplementation on cardiovascular parameters and markers of inflammation and oxidation in patients with coronary vascular disease

Oxidative stress and antioxidant deficiency play a pivotal role in initiation, development, and outcomes of cardiovascular disease. Pharmacokinetic parameters as well as the impact of highly bioavailable lycopene on cardiovascular variables, markers of inflammation and oxidation were investigated during a 30‐day clinical trial in patients with coronary vascular disease. The patients were randomized into two major groups and were supplemented with a single 7 mg daily dose of lycopene ingested either in the form of lactolycopene (68 patients) or in the form of lycosome‐formulated GA lycopene (74 patients). The endpoints included cardiovascular function parameters, serum lipids, and four markers of oxidative stress and inflammation. Ingestion of lycosome‐formulated lycopene increased serum lycopene levels by 2.9‐ and 4.3‐fold, respectively, after 2 and 4 weeks of the trial, whereas supplementation with lactolycopene upregulated serum lycopene by half‐fold only after 4 weeks of ingestion. Lycosome formulation of lycopene resulted by the end of the trial in a threefold reduction in Chlamydia pneumoniae IgG and reduction to the same degree of the inflammatory oxidative damage marker. The decrease in oxidized LDL caused by lycosome‐formulated lycopene was fivefold. Moreover, supplementation with lycosome‐formulated lycopene was accompanied by a significant increase in tissue oxygenation and flow‐mediated dilation by the end of the observational period. In contrast, lactolycopene did not cause any significant changes in the parameters studied. Therefore, enhanced bioavailability of lycopene promotes its antioxidant and anti‐inflammatory functions and endorses a positive effect of lycopene on cardiovascular system

Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase

The elongation of single-stranded DNA repeats at the 3′-ends of chromosomes by telomerase is a key process in maintaining genome integrity in eukaryotes. Abnormal activation of telomerase leads to uncontrolled cell division, whereas its down-regulation is attributed to ageing and several pathologies related to early cell death. Telomerase function is based on the dynamic interactions of its catalytic subunit (TERT) with nucleic acids—telomerase RNA, telomeric DNA and the DNA/RNA heteroduplex. Here, we present the crystallographic and NMR structures of the N-terminal (TEN) domain of TERT from the thermotolerant yeast Hansenula polymorpha and demonstrate the structural conservation of the core motif in evolutionarily divergent organisms. We identify the TEN residues that are involved in interactions with the telomerase RNA and in the recognition of the ‘fork’ at the distal end of the DNA product/RNA template heteroduplex. We propose that the TEN domain assists telomerase biological function and is involved in restricting the size of the heteroduplex during telomere repeat synthesis