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Scientific Reports Apr 2024While particle therapy has been used for decades for cancer treatment, there is still a lack of information on the molecular mechanisms of biomolecules radiolysis by...
While particle therapy has been used for decades for cancer treatment, there is still a lack of information on the molecular mechanisms of biomolecules radiolysis by accelerated ions. Here, we examine the effects of accelerated protons on highly concentrated native myoglobin, by means of Fourier transform infrared and UV-Visible spectroscopies. Upon irradiation, the secondary structure of the protein is drastically modified, from mostly alpha helices conformation to mostly beta elements at highest fluence. These changes are accompanied by significant production of carbon monoxide, which was shown to come from heme degradation under irradiation. The radiolytic yields of formation of denatured protein, carbon monoxide, and of heme degradation were determined, and found very close to each other: G ≈ G ≈ G = 1.6 × 10 ± 0.1 × 10 mol/J = 0.16 ± 0.01 species/100 eV. The denaturation of the protein to a beta structure and the production of carbon monoxide under ion irradiation are phenomena that may play an important role in the biological effects of ionizing radiation.
Topics: Protons; Myoglobin; Carbon Monoxide; Gels; Heme
PubMed: 38616193
DOI: 10.1038/s41598-024-58378-z -
Medicine Apr 2024Acute myocardial infarction (AMI), the most severe cardiovascular event in clinical settings, imposes a significant burden with its annual increase in morbidity and... (Review)
Review
Acute myocardial infarction (AMI), the most severe cardiovascular event in clinical settings, imposes a significant burden with its annual increase in morbidity and mortality rates. However, it is noteworthy that mortality due to AMI in developed countries has experienced a decline, largely attributable to the advancements in medical interventions such as percutaneous coronary intervention. This trend highlights the importance of accurate diagnosis and effective treatment to preserve the myocardium at risk and improve patient outcomes. Conventional biomarkers such as myoglobin, creatine kinase isoenzymes, and troponin have been instrumental in the diagnosis of AMI. However, recent years have witnessed the emergence of new biomarkers demonstrating the potential to further enhance the accuracy of AMI diagnosis. This literature review focuses on the recent advancements in biomarker research in the context of AMI diagnosis.
Topics: Humans; Myocardial Infarction; Myocardium; Biomarkers; Creatine Kinase; Myoglobin
PubMed: 38608048
DOI: 10.1097/MD.0000000000037793 -
The Analyst May 2024A forced, damped harmonic oscillator model for gas-phase ion parking using single-frequency resonance excitation is described and applied to high-mass ions of relevance...
A forced, damped harmonic oscillator model for gas-phase ion parking using single-frequency resonance excitation is described and applied to high-mass ions of relevance to native mass spectrometry. Experimental data are provided to illustrate key findings revealed by the modelling. These include: (i) ion secular frequency spacings between adjacent charge states of a given protein are essentially constant and decrease with the mass of the protein (ii) the mechanism for ion parking of high mass ions is the separation of the ion clouds of the oppositely-charged ions with much less influence from an increase in the relative ion velocity due to resonance excitation, (iii) the size of the parked ion cloud ultimately limits ion parking at high / ratio, and (iv) the extent of ion parking of off-target ions is highly sensitive to the bath gas pressure in the ion trap. The model is applied to ions of 17 kDa, 467 kDa, and 2 MDa while experimental data are also provided for ions of horse skeletal muscle myoglobin (≈17 kDa) and β-galactosidase (≈467 kDa). The model predicts and data show that it is possible to effect ion parking on a 17 kDa protein to the 1 charge state under trapping conditions that are readily accessible with commercially available ion traps. It is also possible to park β-galactosidase efficiently to a roughly equivalent / ratio (, the 26 charge state) under the same trapping conditions. However, as charge states decrease, analyte ion cloud sizes become too large to allow for efficient ion trapping. The model allows for a semi-quantitative prediction of ion trapping performance as a function of ion trapping, resonance excitation, and pressure conditions.
PubMed: 38600834
DOI: 10.1039/d4an00242c -
Frontiers in Nutrition 2024Collagen peptide supplementation in conjunction with exercise has been shown to improve structural and functional adaptations of both muscles and the extracellular...
Reduction in systemic muscle stress markers after exercise-induced muscle damage following concurrent training and supplementation with specific collagen peptides - a randomized controlled trial.
INTRODUCTION
Collagen peptide supplementation in conjunction with exercise has been shown to improve structural and functional adaptations of both muscles and the extracellular matrix. This study aimed to explore whether specific collagen peptide (SCP) supplementation combined with a concurrent training intervention can improve muscular stress after exercise-induced muscle damage, verified by reliable blood markers.
METHODS
55 sedentary to moderately active males participating in a concurrent training (CT) intervention (3x/week) for 12 weeks were administered either 15 g of SCP or placebo (PLA) daily. Before (T1) and after the intervention (T2), 150 muscle-damaging drop jumps were performed. Blood samples were collected to measure creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin (MYO) and high-sensitivity C-reactive protein (hsCRP) before, after, and at 2 h, 24 h and 48 h post exercise.
RESULTS
A combination of concurrent training and SCP administration showed statistically significant interaction effects, implying a lower increase in the area under the curve (AUC) of MYO ( = 0.004, ηp = 0.184), CK ( = 0.01, ηp = 0.145) and LDH ( = 0.016, ηp = 0.133) in the SCP group. On closer examination, the absolute mean differences (ΔAUCs) showed statistical significance in MYO ( = 0.017, = 0.771), CK ( = 0.039, = 0.633) and LDH ( = 0.016, = 0.764) by SCP supplementation.
CONCLUSION
In conclusion, 12 weeks of 15 g SCP supplementation combined with CT intervention reduced acute markers of exercise-induced muscle damage and improved post-exercise regenerative capacity, as evidenced by the altered post-exercise time course. The current findings indicate that SCP supplementation had a positive effect on the early phase of muscular recovery by either improving the structural integrity of the muscle and extracellular matrix during the training period or by accelerating membrane and cytoskeletal protein repair.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov/study/NCT05220371?cond=NCT05220371&rank=1, NCT05220371.
PubMed: 38590831
DOI: 10.3389/fnut.2024.1384112 -
Nature Catalysis Jan 2024Lactam rings are found in many biologically active natural products and pharmaceuticals, including important classes of antibiotics. Methods for the asymmetric synthesis...
Lactam rings are found in many biologically active natural products and pharmaceuticals, including important classes of antibiotics. Methods for the asymmetric synthesis of these molecules are therefore highly desirable, particularly through the selective functionalization of unreactive aliphatic C-H bonds. Here we show the development of a strategy for the asymmetric synthesis of β-, γ-, and δ-lactams via hemoprotein-catalysed intramolecular C-H amidation reaction with readily available dioxazolone reagents. Engineered myoglobin variants serve as excellent biocatalysts for this transformation yielding the desired lactam products in high yields, high enantioselectivity, and on preparative scale. Mechanistic and computational studies elucidate the nature of the C-H amination and enantiodetermining steps and provide insights into protein-mediated control of regioselectivity and stereoselectivity. Additionally, an alkaloid natural product and a drug molecule were synthesized chemoenzymatically in much fewer steps (7-8 vs. 11-12) than previously reported, further demonstrating the power of biosynthetic strategy for the preparation of complex bioactive molecules.
PubMed: 38584987
DOI: 10.1038/s41929-023-01068-2 -
Journal of the International Society of... Dec 2024Rapid regeneration after intense exercise is essential for competitive athletes. Based on this assumption, supplementation strategies, focusing on food supplements, are...
Influence of short-term chronic oral cannabidiol application on muscle recovery and performance after an intensive training protocol - a randomized double-blind crossover study.
BACKGROUND
Rapid regeneration after intense exercise is essential for competitive athletes. Based on this assumption, supplementation strategies, focusing on food supplements, are increasing to improve the recovery processes. One such supplement is cannabidiol (CBD) which is gaining more attention in competitive sports. However, the evidence is still lacking and there are no data available about the effect of a short-term chronic application.
METHODS
A three-arm double-blind cross-over study was conducted to determine the effects of two different CBD products on performance, muscle damage and inflammatory processes in well-trained athletes. In total 17 subjects took successfully part in this study. Each subject underwent the six-day, high-intensity training protocol three times. After each training session, each subject took either a placebo or a CBD product (60 mg of oil or solubilisate). Between the intervention phases, at least four weeks of washout period was conducted. Before and after the training protocols the performance capacity in countermovement jump (CMJ), back squat (BS), bench press (BP) and 1-mile run were measured and biomarkers for muscle damage (creatine kinase, myoglobin), inflammatory processes (interleukin 6 and 10) and immune cell activity (ratios of neutrophil granulocytes, lymphocytes and, platelets) were analyzed. For statistical analyses, the current version of R and a linear mixed model was used.
RESULTS
It could identify different effects of the training protocol depending on performance level (advanced or highly advanced athletes) ( < .05). Regardless of the performance level, muscle damage and a reduction in performance could be induced by the training protocol. Only CBD oil was associated with a reduction in myoglobin concentration ( < .05) in advanced athletes. Concerning immune activity, a significant decrease in platelets lymphocyte ratios was observed in advanced athletes after placebo treatment ( < .05). CBD oil application showed a slight inhibitory effect ( < .10). Moreover, the reduction in performance differs between the performance levels. A significant decrease in CMJ was observed in advanced athletes and a decreasing trend in BS was observed in highly advanced athletes after placebo treatment ( < 0.10). Both CBD products do not affect performance parameters. For inflammatory parameters, no effects were observed.
CONCLUSION
It was found that the performance level of the subjects was a decisive factor and that they responded differently to the training protocol and the CBD application. However, no clear effects of either CBD product were found and further research is needed to identify the long-term effects of CBD application.
Topics: Humans; Cross-Over Studies; Cannabidiol; Myoglobin; Sports; Muscle, Skeletal; Athletes; Double-Blind Method; Dietary Supplements; Randomized Controlled Trials as Topic
PubMed: 38572744
DOI: 10.1080/15502783.2024.2337252 -
BioRxiv : the Preprint Server For... Mar 2024Gene replacement therapies in genetic medicine primarily rely on adeno-associated viral (AAV) vectors for transgene expression. However, episomal expression can decline...
Gene replacement therapies in genetic medicine primarily rely on adeno-associated viral (AAV) vectors for transgene expression. However, episomal expression can decline over time due to epigenetic silencing. CRISPR-based integration methods offer promise for long-term transgene insertion. While the development of transgene integration methods has made substantial progress, identifying optimal insertion loci remains challenging. Skeletal muscle is a promising tissue for gene replacement owing to the ease of access, relative proportion of body mass, the multinucleated nature of muscle, and the potential for reduced adverse effects. Leveraging endogenous promoters in skeletal muscle, we evaluated two high-expressing loci using homology-independent targeted integration (HITI) to integrate reporter or therapeutic genes in mouse myoblasts. We hijacked the muscle creatine kinase (Ckm) and myoglobin (Mb) promoters by co-delivering CRISPR-Cas9 and a donor plasmid with promoterless constructs encoding green fluorescent protein (GFP) or human Factor IX (hFIX). Additionally, we deeply profiled our genome and transcriptome outcomes from targeted integration and evaluated the safety of the proposed sites. This study introduces a proof-of-concept technology for achieving high-level therapeutic gene expression in skeletal muscle, with potential applications in targeted integration-based medicine and synthetic biology.
PubMed: 38562818
DOI: 10.1101/2024.03.18.582796 -
Foods (Basel, Switzerland) Mar 2024The objective of this study was to evaluate the viability and performance of nitric oxide modified-atmosphere packaging (MAP) as a novel alternative to high oxygen and...
The objective of this study was to evaluate the viability and performance of nitric oxide modified-atmosphere packaging (MAP) as a novel alternative to high oxygen and carbon monoxide MAP for ground beef. Packages of ground beef under high oxygen (HI-OX), carbon monoxide (CO), and nitric oxide (NO) atmospheres were evaluated for descriptive and instrumental color every 12 h during a 120 h display period. Surface myoglobin percentages, internal cooked color, thiobarbituric acid reactive substances (TBARS), and residual nitrite and nitrate were also evaluated. There were gas × time interactions for descriptive color, discoloration, a* values, b* values, deoxymyoglobin percentages, and metmyoglobin percentages ( < 0.05). There were also gas-type main effects for cooked color and TBARS ( < 0.05). Carbon monoxide maintained the most redness and least discoloration throughout the display period, while HI-OX started with a bright red color but rapidly browned ( < 0.05). Nitric oxide started as dark red to tannish-red but transitioned to a dull red ( < 0.05). However, NO had increased redness and a* values for internal cooked color ( < 0.05). Although CO outperformed NO packages, NO exhibited a unique color cycle warranting further research to optimize its use.
PubMed: 38540892
DOI: 10.3390/foods13060902 -
Journal of Biomedical Optics Mar 2024Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critically ill patients. The process of...
Combined frequency domain near-infrared spectroscopy and diffuse correlation spectroscopy system for comprehensive metabolic monitoring of inspiratory muscles during loading.
SIGNIFICANCE
Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critically ill patients. The process of weaning patients from MV can be long and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles.
AIM
The goal of this project was to develop and validate a combined frequency domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load.
APPROACH
The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young, healthy volunteers. Volunteers performed two different respiratory exercises, a moderate load and a high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period.
RESULTS
The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (), and metabolic rate of oxygen () compared with hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in , and were observed compared with Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation.
CONCLUSIONS
The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics.
Topics: Humans; Male; Female; Spectroscopy, Near-Infrared; Oxygen; Hemoglobins; Oxyhemoglobins; Oxygen Consumption; Muscles; Muscle, Skeletal
PubMed: 38532926
DOI: 10.1117/1.JBO.29.3.035002 -
Frontiers in Physiology 2024Heavy strength (HS) and short-sprint (SS) are commonly used training methods for competitive road cyclists, with the aim to improve the anaerobic power and short time...
Heavy strength (HS) and short-sprint (SS) are commonly used training methods for competitive road cyclists, with the aim to improve the anaerobic power and short time cycling performance. Knowledge of how such training methods affects biochemical as well as molecular factors, are particularly important for determining individual recovery and long-term adaptations. The primary aim of the current study was to investigate the expression levels of small non-coding RNAs in response to HS and SS training in elite cyclists as potential biomarkers for individual optimal restitution time. Eleven well trained cyclists performed one session of HS training and one session of SS training on separate days. Blood samples were taken at baseline and 5 min, 1 h and 21 h post training. Along with physiological measurements and biochemical factors (serum creatine kinase, myoglobin, human growth hormone and plasma lactate), real-time quantitative PCR was used to explore whether HS and/or SS training influenced the abundance of 24 circulating miRNAs, in serum, associated with muscle development, angiogenesis, and/or inflammation. Based on complete miRNA profiles from nine cyclists, the miRNAs showing most altered expression after both training sessions included the three striated muscle-specific miRNAs (myomiRs) miR-1-3p, 133a-3p and 133b-3p. While all three miRNAs showed significantly highest expression at 1 h post HS session, the acute effect of the SS session included a significantly higher level of miR-1-3p alone, at 5 min (highest), as well as at 1 h and 21 h post session. Correlation (negative) with biochemical markers was only shown for miR-133a-3p and CK (r = -0.786, = 0.041) and between miR-133b-3p and [La] (r = -0.711, = .032), at 21 h post SS session. Our findings support that unique myomiRs are regulated by HS and SS training. Such knowledge may be important for individually adjusted restitution times.
PubMed: 38532845
DOI: 10.3389/fphys.2024.1365357