Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Rising of intracellular NAD+ level and oppositely directed changes in CD38 expression in hippocampal cells in experimental Alzheimer's disease

The aim of the study was to assess the level of NAD+ in the brain of mice treated with beta-amyloid (Aβ), as well as to determine the activity of ADP-ribosyl cyclase/CD38 and the number of CD38-immunopositive neurons, astrocytes and endothelial cells. Material and methods. The Alzheimer's disease model was reproduced by intrahippocampal administration of Aβ to C57BL/6 mice. Determination of the NAD+ level in the extracellular fluid of the brain and in the hippocampal tissue was carried out by spectrophotometric analysis. Evaluation of the enzymatic activity of ADP-ribosyl cyclase/CD38 was carried out by the fluorimetric method, determination of the number of CD38-immunopositive cells by the immunohistochemistry method. Results and discussion. The level of NAD+ was significantly increased in the hippocampal tissue in mice after administration of Aβ, while the level of extracellular NAD+ did not change. The activity of ADP-ribosyl cyclase/CD38 in the hippocampal tissue did not change, but the number of CD38-immunopositive neurons decreased, and the number of CD38+ endothelial cells increased in the hippocampus of mice after administration of Aβ. Conclusion. Opposite changes in the expression of ADP-ribosyl cyclase / CD38 in neurons and endotheliocytes correspond to different metabolic states of these types of cells and, along with an increased intracellular pool of NAD+ in experimental Alzheimer's disease, reflect an adaptive stress response to Aβ administration

Chiral Dualism as a Unifying Principle in Molecular Biophysics

The origin and potential role of chiral asymmetry remain one of the most exciting issues in biology. In this paper we review the chirality of biological macromolecules, starting at the level of single molecules and continuing to the level of supramolecular assemblies. We discuss the physical and chemical consequences of the presence of chirality and their role in the self-organization and formation of structural hierarchies in cells. Homochirality may serve as an essential factor that invokes mechanisms required to control the formation of discrete structural hierarchies in macromolecules and macromolecular assemblies. Symmetry is of fundamental importance not only for all molecular biology as a systemic factor of its organization but also for pharmacology, as well as a systemic factor of drug stereospecificity

Effect of UV Stress on the Antioxidant Capacity, Photosynthetic Activity, Flavonoid and Steviol Glycoside Accumulation of <i>Stevia rebaudiana</i> Bertoni

Lighting conditions are an important controller of plant growth and development, and they affect secondary metabolite synthesis. In this research, we explored the effect of additional UV irradiation of various ranges in addition to the main one at PPFD 160 µmol m−2 s−1 on the accumulation of some secondary metabolites of stevia (Stevia rebaudiana Bertoni). The fresh weight of leaves was slightly higher under additional UV-A and UV-B irradiation compared with the control variant, and the leaf surface area was significantly larger, respectively, by 23.3 and 20.7% than in the control variant, while the rate of photosynthesis did not decrease. Plants under additional UV-B and UV-C irradiation were under the greatest light stress, as evidenced by a decrease in antioxidant capacity by an average of 30% compared to the control and UV-A. The total flavonoid content was significantly higher (by 74%) under UV-B irradiation. The highest concentration of steviol glycoside was observed during budding and flowering under UV-B and UV-C irradiation (by 13.2 and 11.3%, respectively). Analysis of hyperspectral images, chlorophyll fluorescence, and vegetation indices showed light stress increasing under UV-C irradiation, which caused an increase in the relative chlorophyll content, scorches, leaf morphology changes, a CO2 absorption rate decrease, and plant growth inhibition. UV-B irradiation can be used as an optimal type of irradiation based on a set of indicators

Evaluation of the Effectiveness of Different LED Irradiators When Growing Red Mustard (<i>Brassica juncea</i> L.) in Indoor Farming

Investigation is devoted to the optimization of light spectrum and intensity used for red mustard growing. Notably, most of the studies devoted to red mustard growing were conducted on micro-greens, which is not enough for the development of methods and recommendations for making the right choices about the irradiation parameters for full-cycle cultivation. In this study, we tested four models of LED with different ratios of blue, green red and far red radiation intensity: 12:20:63:5; 15:30:49:6; 30:1:68:1, in two values of photon flux density (PFD)—120 and 180 µmol m−2 s−1—to determine the most effective combination for red mustard growing. The study was conducted in a container-type climate chamber, where the red leaf mustard was cultivated in hydroponics. On the 30th day of cultivation, the plant’s morphological, biochemical and chlorophyll fluorescence parameters, and reflection coefficients were recorded. The results indicated that the PFD 120 µmol m−2 s−1 had a worse effect on both mustard leaf biomass accumulation and nitrate concentration (13–30% higher) in the plants. The best lighting option for growing red mustard was the blue–red spectrum, as the most efficient in terms of converting electricity into biomass (77 Wth/g). This light spectrum contributes to plant development with a larger leaf area (60%) and a fresh mass (54%) compared with the control, which has a maximum similarity in spectrum percentage to the sunlight spectrum. The presence of green and far red radiation with the blue–red light spectrum in various proportions at the same level of PFD had a negative effect on plant fresh mass, leaf surface area and photosynthetic activity. The obtained results could be useful for lighting parameters’ optimization when growing red mustard in urban farms

Evaluation of the Effectiveness of Different LED Irradiators When Growing Red Mustard (Brassica juncea L.) in Indoor Farming

Investigation is devoted to the optimization of light spectrum and intensity used for red mustard growing. Notably, most of the studies devoted to red mustard growing were conducted on micro-greens, which is not enough for the development of methods and recommendations for making the right choices about the irradiation parameters for full-cycle cultivation. In this study, we tested four models of LED with different ratios of blue, green red and far red radiation intensity: 12:20:63:5; 15:30:49:6; 30:1:68:1, in two values of photon flux density (PFD)&mdash;120 and 180 &micro;mol m&minus;2 s&minus;1&mdash;to determine the most effective combination for red mustard growing. The study was conducted in a container-type climate chamber, where the red leaf mustard was cultivated in hydroponics. On the 30th day of cultivation, the plant&rsquo;s morphological, biochemical and chlorophyll fluorescence parameters, and reflection coefficients were recorded. The results indicated that the PFD 120 &micro;mol m&minus;2 s&minus;1 had a worse effect on both mustard leaf biomass accumulation and nitrate concentration (13&ndash;30% higher) in the plants. The best lighting option for growing red mustard was the blue&ndash;red spectrum, as the most efficient in terms of converting electricity into biomass (77 Wth/g). This light spectrum contributes to plant development with a larger leaf area (60%) and a fresh mass (54%) compared with the control, which has a maximum similarity in spectrum percentage to the sunlight spectrum. The presence of green and far red radiation with the blue&ndash;red light spectrum in various proportions at the same level of PFD had a negative effect on plant fresh mass, leaf surface area and photosynthetic activity. The obtained results could be useful for lighting parameters&rsquo; optimization when growing red mustard in urban farms

Impact of Ultraviolet Radiation on the Pigment Content and Essential Oil Accumulation in Sweet Basil (Ocimum basilicum L.)

In this study, we investigated the effects of additional ultraviolet radiation (UV) on the main growth fluorescent lamp light on pigment content and essential oil accumulation in sweet basil (Ocimum basilicum L.). Three different UV light sources from light-emitting diodes and discharge lamps, which emit UV in the UV-A (315&ndash;400 nm), UV-B (280&ndash;315 nm) and UV-C (100&ndash;280 nm) ranges, were tested for basil plant growing. The plants, growing under additional UV-A and UV-B from mercury lamps, on the 60th growing day were higher than control plants by 90% and 53%, respectively. The fresh leaf mass of the UV-A irradiated basil plants was 2.4-fold higher than the control plant mass. The dry mass/fresh mass ratio of the UV-A and UV-B irradiated plants was higher by 45% and 35% in comparison to the control plants. Leaf area was increased by 40% and 20%, respectively. UV-C affected the anthocyanin content most strongly, they increased by 50%, whereas only by 27% and 0% under UV-A and UV-B. Any UV addition did not affect the essential oil total contents but altered the essential oil compositions. UV-A and UV-B increased the linalool proportion from 10% to 20%, and to 25%, respectively, in contrast to UV-C, which reduced it to 3%. UV-C induced the eugenol methyl ether accumulation (17%) and inhibited plant growth. Moreover, UV increased the proportion of &alpha;-guaiene, &beta;-cubebene and &alpha;-bulnesene and decreased the proportion of sabinene and fenchone. Thus, we concluded that UV (except UV-C) used jointly with main light with PPFD 120 &plusmn; 10 &mu;mol photons&middot;m&minus;2&middot;s&minus;1 for sweet basil cultivation may be justified to stimulate basil growth and optimize the essential oil accumulation

Impact of Ultraviolet Radiation on the Pigment Content and Essential Oil Accumulation in Sweet Basil (<i>Ocimum basilicum</i> L.)

In this study, we investigated the effects of additional ultraviolet radiation (UV) on the main growth fluorescent lamp light on pigment content and essential oil accumulation in sweet basil (Ocimum basilicum L.). Three different UV light sources from light-emitting diodes and discharge lamps, which emit UV in the UV-A (315–400 nm), UV-B (280–315 nm) and UV-C (100–280 nm) ranges, were tested for basil plant growing. The plants, growing under additional UV-A and UV-B from mercury lamps, on the 60th growing day were higher than control plants by 90% and 53%, respectively. The fresh leaf mass of the UV-A irradiated basil plants was 2.4-fold higher than the control plant mass. The dry mass/fresh mass ratio of the UV-A and UV-B irradiated plants was higher by 45% and 35% in comparison to the control plants. Leaf area was increased by 40% and 20%, respectively. UV-C affected the anthocyanin content most strongly, they increased by 50%, whereas only by 27% and 0% under UV-A and UV-B. Any UV addition did not affect the essential oil total contents but altered the essential oil compositions. UV-A and UV-B increased the linalool proportion from 10% to 20%, and to 25%, respectively, in contrast to UV-C, which reduced it to 3%. UV-C induced the eugenol methyl ether accumulation (17%) and inhibited plant growth. Moreover, UV increased the proportion of α-guaiene, β-cubebene and α-bulnesene and decreased the proportion of sabinene and fenchone. Thus, we concluded that UV (except UV-C) used jointly with main light with PPFD 120 ± 10 μmol photons·m−2·s−1 for sweet basil cultivation may be justified to stimulate basil growth and optimize the essential oil accumulation