Influence of Higenamine on Exercise Performance of Recreational Female Athletes: A Randomized Double-Blinded Placebo-Controlled Trial

The aim of this study was to determine the ergogenic effects and the safety profile of a one-component higenamine supplement in female recreational athletes. Twelve recreational female basketball players (age 29–41 years, oxygen consumption (VO2max) > 30 ml⋅kg–1⋅min–1, with training > 5 h wk–1) were randomized either to the higenamine group, or to the placebo group for 3 weeks. In order to determine ergogenic effects and safety profile of higenamine administration, we assessed the following variables before and after 3 weeks of supplementation: anthropometric parameters, resting metabolic rate (RMR), exercise testing variables, serum free fatty acids (FFAs), blood pressure, enzyme activity, urea, lipid profile, and complete blood count. There were no differences between groups in anthropometric parameters, including basal metabolic rate (BMR), RMR and body fat [p = 0.706 (Cohen’s d 0.223), p = 0.169 (Cohen’s d 0.857), and p = 0.223 (Cohen’s d 0.750), respectively], FFAs [0.43 ± 0.03 vs. 0.54 ± 0.23, p = 0.206 (Cohen’s d 0.540)], neither significant differences in cardiopulmonary parameters after the intervention period. Furthermore, all measured outcome variables in the safety assessment were not significant, with values remaining stable during the intervention period for participants in both groups. This is the first study to document the effects and the safety profile of higenamine-based dietary supplements at a specified dose in female recreational athletes. Our data indicate that 21-day of supplementation with 75 mg higenamine would not result in improving cardiopulmonary exercise fitness and weight loss in female recreational athletes. Moreover, supplementation with 75 mg higenamine is safe and well-tolerated in younger recreational female athletes

The HPLC determination of the content of magnoflorine in Epimedium alpinum L.

The aporphine alkaloid magnoflorine, known as a constituent of Asian Epimedium species, was isolated for the first time from the wild growing European species, Epimedium alpinum L. Identification was done by comparison with literature data. The HPLC method was applied for the determination of the content of the alkaloid in methanolic extracts of plant material. The underground part of E. alpinum contains 1–2 % of magnoflorine, while its content in methanolic extracts was 9.2–11.8 %. The aerial part of the plant contains less alkaloid (0.06–0.12 %), while the magnoflorine content in methanolic extracts of the aerial part was 0.4–0.8 %. Probably, the high content of magnoflorine in the methanolic extracts of underground parts of E. alpinum influences its dose-dependent cytotoxic activity (300 mg/ml; 39 % survival of cells in an experimental K562 cell culture)

Nitrogen Oxide Atom-Transfer Redox Chemistry; Mechanism of NO_(g) to Nitrite Conversion Utilizing μ‑oxo Heme-Fe^III–O–Cu^II(L) Constructs

While nitric oxide (NO, nitrogen monoxide) is a critically important signaling agent, its cellular concentrations must be tightly controlled, generally through its oxidative conversion to nitrite (NO₂^–) where it is held in reserve to be reconverted as needed. In part, this reaction is mediated by the binuclear heme a₃/Cu_B active site of cytochrome <i>c</i> oxidase. In this report, the oxidation of NO_(g) to nitrite is shown to occur efficiently in new synthetic μ-oxo heme-Fe^III–O–Cu^II(L) constructs (L being a tridentate or tetradentate pyridyl/alkylamino ligand), and spectroscopic and kinetic investigations provide detailed mechanistic insights. Two new X-ray structures of μ-oxo complexes have been determined and compared to literature analogs. All μ-oxo complexes react with 2 mol equiv NO_(g) to give 1:1 mixtures of discrete [(L)­Cu^II(NO₂^–)]⁺ plus ferrous heme-nitrosyl compounds; when the first NO_(g) equiv reduces the heme center and itself is oxidized to nitrite, the second equiv of NO_(g) traps the ferrous heme thus formed. For one μ-oxo heme-Fe^III–O–Cu^II(L) compound, the reaction with NO_(g) reveals an intermediate species (“intermediate”), formally a bis-NO adduct, [(NO)­(porphyrinate)­Fe^II–(NO₂^–)–Cu^II(L)]⁺ (λ_max = 433 nm), confirmed by cryo-spray ionization mass spectrometry and EPR spectroscopy, along with the observation that cooling a 1:1 mixture of [(L)­Cu^II(NO₂^–)]⁺ and heme-Fe^II(NO) to −125 °C leads to association and generation of the key 433 nm UV–vis feature. Kinetic-thermodynamic parameters obtained from low-temperature stopped-flow measurements are in excellent agreement with DFT calculations carried out which describe the sequential addition of NO_(g) to the μ-oxo complex

Selective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration

Life on Earth emerged in a hydrogen sulfide (H2S)-rich environment eons ago and with it protein persulfidation mediated by H2S evolved as a signaling mechanism. Protein persulfidation (S-sulfhydration) is a post-translational modification of reactive cysteine residues, which modulate protein structure and/or function. Persulfides are difficult to label and study due to their reactivity and similarity with cysteine. Here, we report a facile strategy for chemoselective persulfide bioconjugation using dimedone-based probes, to achieve highly selective, rapid, and robust persulfide labeling in biological samples with broad utility. Using this method, we show persulfidation is an evolutionarily conserved modification and waves of persulfidation are employed by cells to resolve sulfenylation and prevent irreversible cysteine overoxidation preserving protein function. We report an age-associated decline in persulfidation that is conserved across evolutionary boundaries. Accordingly, dietary or pharmacological interventions to increase persulfidation associate with increased longevity and improved capacity to cope with stress stimuli

Intraclonal Complexity in Chronic Lymphocytic Leukemia: Fractions Enriched in Recently Born/Divided and Older/Quiescent Cells

The failure of chemotherapeutic regimens to eradicate cancers often results from the outgrowth of minor subclones with more dangerous genomic abnormalities or with self-renewing capacity. To explore such intratumor complexities in B-cell chronic lymphocytic leukemia (CLL), we measured B-cell kinetics in vivo by quantifying deuterium (2H)-labeled cells as an indicator of a cell that had divided. Separating CLL clones on the basis of reciprocal densities of chemokine (C-X-C motif) receptor 4 (CXCR4) and cluster designation 5 (CD5) revealed that the CXCR4dimCD5bright (proliferative) fraction contained more 2H-labeled DNA and hence divided cells than the CXCR4brightCD5dim (resting) fraction. This enrichment was confirmed by the relative expression of two cell cycle–associated molecules in the same fractions, Ki-67 and minichromosome maintenance protein 6 (MCM6). Comparisons of global gene expression between the CXCR4dimCD5bright and CXCR4brightCD5dim fractions indicated higher levels of pro-proliferation and antiapoptotic genes and genes involved in oxidative injury in the proliferative fraction. An extended immunophenotype was also defined, providing a wider range of surface molecules characteristic of each fraction. These intraclonal analyses suggest a model of CLL cell biology in which the leukemic clone contains a spectrum of cells from the proliferative fraction, enriched in recently divided robust cells that are lymphoid tissue emigrants, to the resting fraction enriched in older, less vital cells that need to immigrate to lymphoid tissue or die. The model also suggests several targets preferentially expressed in the two populations amenable for therapeutic attack. Finally, the study lays the groundwork for future analyses that might provide a more robust understanding of the development and clonal evolution of this currently incurable disease

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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