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Frontiers in Neuroscience 2024White matter hyperintensities (WMHs), presented on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequences, are lesions in the...
BACKGROUND AND AIM
White matter hyperintensities (WMHs), presented on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequences, are lesions in the human brain that can be observed in both migraine and multiple sclerosis (MS).
METHODS
Seventeen migraine patients and 15 patients with relapsing-remitting multiple sclerosis with WMHs, and 17 healthy subjects age-and sex-matched to the migraine group were prospectively enrolled and underwent conventional and advanced MRI studies with diffusion-and perfusion-weighted imaging and single voxel proton magnetic resonance spectroscopy.
RESULTS
In both disease groups, elevated T2 relaxation time, apparent diffusion coefficient (ADC) values, and decreased -acetyl-aspartate levels were found in the intralesional white matter compared to the contralateral normal-appearing white matter (NAWM), while there was no difference between the hemispheres of the control subjects. Migraine patients had the lowest intralesional creatine + phosphocreatine and myo-inositol (mI) values among the three groups, while patients with MS showed the highest intralesional T1 and T2 relaxation times, ADC, and mI values. In the contralateral NAWM, the same trend with mI changes was observed in migraineurs and MS patients. No differences in perfusion variables were observed in any groups.
CONCLUSION
Our multimodal study showed that tissue damage is detectable in both diseases. Despite the differences in various advanced MRI measures, with more severe injury detected in MS lesions, we could not clearly differentiate the two white matter lesion types.
PubMed: 38784095
DOI: 10.3389/fnins.2024.1384073 -
BMC Psychiatry Apr 2024H-MRS is increasingly used in basic and clinical research to explain brain function and alterations respectively. In psychosis research it is now one of the main tools...
BACKGROUND
H-MRS is increasingly used in basic and clinical research to explain brain function and alterations respectively. In psychosis research it is now one of the main tools to investigate imbalances in the glutamatergic system. Interestingly, however, the findings are extremely variable even within patients of similar disease states. One reason may be the variability in analysis strategies, despite suggestions for standardization. Therefore, our study aimed to investigate the extent to which the basis set configuration- which metabolites are included in the basis set used for analysis- would affect the spectral fit and estimated glutamate (Glu) concentrations in the anterior cingulate cortex (ACC), and whether any changes in levels of glutamate would be associated with psychotic-like experiences and autistic traits.
METHODS
To ensure comparability, we utilized five different exemplar basis sets, used in research, and two different analysis tools, r-based spant applying the ABfit method and Osprey using the LCModel.
RESULTS
Our findings revealed that the types of metabolites included in the basis set significantly affected the glutamate concentration. We observed that three basis sets led to more consistent results across different concentration types (i.e., absolute Glu in mol/kg, Glx (glutamate + glutamine), Glu/tCr), spectral fit and quality measurements. Interestingly, all three basis sets included phosphocreatine. Importantly, our findings also revealed that glutamate levels were differently associated with both schizotypal and autistic traits depending on basis set configuration and analysis tool, with the same three basis sets showing more consistent results.
CONCLUSIONS
Our study highlights that scientific results may be significantly altered depending on the choices of metabolites included in the basis set, and with that emphasizes the importance of carefully selecting the configuration of the basis set to ensure accurate and consistent results, when using MR spectroscopy. Overall, our study points out the need for standardized analysis pipelines and reporting.
Topics: Humans; Gyrus Cinguli; Glutamic Acid; Male; Adult; Female; Proton Magnetic Resonance Spectroscopy; Young Adult; Personality; Psychotic Disorders; Magnetic Resonance Spectroscopy; Glutamine
PubMed: 38664663
DOI: 10.1186/s12888-024-05646-x -
Bioresources and Bioprocessing Jun 2023Cell-free protein synthesis (CFPS) system is an ideal platform for fast and convenient protein research and has been used for macromolecular assembly, unnatural amino...
Cell-free protein synthesis (CFPS) system is an ideal platform for fast and convenient protein research and has been used for macromolecular assembly, unnatural amino acid embedding, glycoprotein production, and more. To realize the construction of an efficient eukaryotic CFPS platform with the advantages of low cost and short time, a CFPS system based on the yeast Pichia pastoris was built in this study. The internal ribosomal entry site (IRES) can independently initiate translation and thus promote protein synthesis. The Kozak sequences can facilitate translation initiation. Therefore, the screening of IRES and its combination with Kozak was performed, in which cricket paralysis virus (CRPV) exhibited as the best translation initiation element from 14 different IRESs. Furthermore, the system components and reaction environment were explored. The protein yield was nearly doubled by the addition of RNase inhibitor. The cell extract amount, energy regeneration system (phosphocreatine and phosphocreatine kinase), and metal ions (K and Mg) were optimized to achieve the best protein synthesis yield. This P. pastoris CFPS system can extend the eukaryotic CFPS platform, providing an enabling technology for fast prototyping design and functional protein synthesis.
PubMed: 38647944
DOI: 10.1186/s40643-023-00653-4 -
Clinical Science (London, England :... Apr 2024The non-stop provision of chemical energy is of critical importance to normal cardiac function, requiring the rapid turnover of ATP to power both relaxation and... (Review)
Review
The non-stop provision of chemical energy is of critical importance to normal cardiac function, requiring the rapid turnover of ATP to power both relaxation and contraction. Central to this is the creatine kinase (CK) phosphagen system, which buffers local ATP levels to optimise the energy available from ATP hydrolysis, to stimulate energy production via the mitochondria and to smooth out mismatches between energy supply and demand. In this review, we discuss the changes that occur in high-energy phosphate metabolism (i.e., in ATP and phosphocreatine) during ischaemia and reperfusion, which represents an acute crisis of energy provision. Evidence is presented from preclinical models that augmentation of the CK system can reduce ischaemia-reperfusion injury and improve functional recovery. Energetic impairment is also a hallmark of chronic heart failure, in particular, down-regulation of the CK system and loss of adenine nucleotides, which may contribute to pathophysiology by limiting ATP supply. Herein, we discuss the evidence for this hypothesis based on preclinical studies and in patients using magnetic resonance spectroscopy. We conclude that the correlative evidence linking impaired energetics to cardiac dysfunction is compelling; however, causal evidence from loss-of-function models remains equivocal. Nevertheless, proof-of-principle studies suggest that augmentation of CK activity is a therapeutic target to improve cardiac function and remodelling in the failing heart. Further work is necessary to translate these findings to the clinic, in particular, a better understanding of the mechanisms by which the CK system is regulated in disease.
Topics: Humans; Creatine Kinase; Adenosine Triphosphate; Heart; Heart Failure; Energy Metabolism; Reperfusion Injury; Phosphocreatine; Chronic Disease; Myocardium
PubMed: 38639724
DOI: 10.1042/CS20230616 -
BioMed Research International 2024Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias, and cardiomyocyte dysfunction that may cause...
Hypertrophic cardiomyopathy (HCM) is characterised by asymmetric left ventricular hypertrophy, ventricular arrhythmias, and cardiomyocyte dysfunction that may cause sudden death. HCM is associated with mutations in sarcomeric proteins and is usually transmitted as an autosomal-dominant trait. The aim of this study was to assess the mechanisms that underlie the altered electrophysiological activity, contractility, regulation of energy metabolism, and crossbridge cycling in HCM at the single-cell level. To investigate this, we developed a human ventricular cardiomyocyte model that incorporates electrophysiology, metabolism, and force generation. The model was validated by its ability to reproduce the experimentally observed kinetic properties of human HCM induced by (a) remodelling of several ion channels and Ca-handling proteins arising from altered Ca/calmodulin kinase II signalling pathways and (b) increased Ca sensitivity of the myofilament proteins. Our simulation showed a decreased phosphocreatine-to-ATP ratio (-9%) suggesting a negative mismatch between energy expenditure and supply. Using a spatial myofilament half-sarcomere model, we also compared the fraction of detached, weakly bound, and strongly bound crossbridges in the control and HCM conditions. Our simulations showed that HCM has more crossbridges in force-producing states than in the control condition. In conclusion, our model reveals that impaired crossbridge kinetics is accompanied by a negative mismatch between the ATP supply and demand ratio. This suggests that improving this ratio may reduce the incidence of sudden death in HCM.
Topics: Humans; Myocytes, Cardiac; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiomyopathy, Hypertrophic; Mutation; Calcium Signaling; Adenosine Triphosphate; Death, Sudden
PubMed: 38567164
DOI: 10.1155/2024/6160554 -
Scientific Reports Mar 2024Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying...
Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males. Cases reported ≥ moderate muscle-weakness to match the organ assessed to an organ affected; controls lacked recent headache or multiple symptoms. The expansion sample added cases without muscle-weakness, controls with recent headache, females, nonwhites. PCr-R, following pedal-depression-exercise, was compared in veterans with GWI versus controls (sample N = 38). In the replication sample, PCr-R results closely matched the prior report: PCr-R veterans with GWI mean(SD) = 47.7(16.5); control mean(SD) = 30.3(9.2), p = 0.017. (Prior-study PCr-R veterans with GWI mean(SD) = 46.1(17.9), control mean(SD) = 29.0(8.7), p = 0.023. Combined replication + prior samples: p = 0.001.) No case-control difference was observed in the expansion sample. In cases, PCr-R related to muscle-weakness: PCr-R = 29.9(7.1), 38.2(8.9), 47.8(15.2) for muscle-weakness rated none/low, intermediate, and high respectively (p for trend = 0.02), validating desirability of matching tissue assessed to tissue affected. In controls, headache/multiple symptoms, sex, and ethnicity each mattered (affecting PCr-R significantly). This study affirms mitochondrial/bioenergetic impairment in veterans with GWI. The importance of careful case/control selection is underscored.
Topics: Male; Female; Humans; Persian Gulf Syndrome; Veterans; Mitochondria; Headache; Paresis; Energy Metabolism
PubMed: 38548808
DOI: 10.1038/s41598-024-57725-4 -
PloS One 2024In vivo noninvasive imaging of neurometabolites is crucial to improve our understanding of the underlying pathophysiological mechanism in neurodegenerative diseases....
In vivo noninvasive imaging of neurometabolites is crucial to improve our understanding of the underlying pathophysiological mechanism in neurodegenerative diseases. Abnormal changes in synaptic organization leading to synaptic degradation and neuronal loss is considered as one of the primary factors driving Alzheimer's disease pathology. Magnetic resonance based molecular imaging techniques such as chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) can provide neurometabolite specific information which may relate to underlying pathological and compensatory mechanisms. In this study, CEST and short echo time single voxel MRS was performed to evaluate the sensitivity of cerebral metabolites to beta-amyloid (Aβ) induced synaptic deficit in the hippocampus of a mouse model of Alzheimer's disease. The CEST based spectra (Z-spectra) were acquired on a 9.4 Tesla small animal MR imaging system with two radiofrequency (RF) saturation amplitudes (1.47 μT and 5.9 μT) to obtain creatine-weighted and glutamate-weighted CEST contrasts, respectively. Multi-pool Lorentzian fitting and quantitative T1 longitudinal relaxation maps were used to obtain metabolic specific apparent exchange-dependent relaxation (AREX) maps. Short echo time (TE = 12 ms) single voxel MRS was acquired to quantify multiple neurometabolites from the right hippocampus region. AREX contrasts and MRS based metabolite concentration levels were examined in the ARTE10 animal model for Alzheimer's disease and their wild type (WT) littermate counterparts (age = 10 months). Using MRS voxel as a region of interest, group-wise analysis showed significant reduction in Glu-AREX and Cr-AREX in ARTE10, compared to WT animals. The MRS based results in the ARTE10 mice showed significant decrease in glutamate (Glu) and glutamate-total creatine (Glu/tCr) ratio, compared to WT animals. The MRS results also showed significant increase in total creatine (tCr), phosphocreatine (PCr) and glutathione (GSH) concentration levels in ARTE10, compared to WT animals. In the same ROI, Glu-AREX and Cr-AREX demonstrated positive associations with Glu/tCr ratio. These results indicate the involvement of neurotransmitter metabolites and energy metabolism in Aβ-mediated synaptic degradation in the hippocampus region. The study also highlights the feasibility of CEST and MRS to identify and track multiple competing and compensatory mechanisms involved in heterogeneous pathophysiology of Alzheimer's disease in vivo.
Topics: Mice; Animals; Creatine; Alzheimer Disease; Magnetic Resonance Imaging; Animals, Wild; Glutamic Acid; Receptors, Antigen, T-Cell
PubMed: 38483851
DOI: 10.1371/journal.pone.0299961 -
Journal of Exercise Science and Fitness Apr 2024Due to the character of the taekwondo, the adenosine triphosphate-phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated...
The enhancement of explosive power contributes to the development of anaerobic capacity: A comparison of autoregulatory progressive resistance exercise and velocity-based resistance training.
OBJECTIVES
Due to the character of the taekwondo, the adenosine triphosphate-phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated execution of kicks, and the aerobic system promotes recovery between these movements and the bout. Therefore, taekwondo athletes require high explosive power and anaerobic capacity in order to carry out sustained and powerful attacks. So, the purpose of this study is to compare the effects of APRE and VBRT on lower-limb explosive power and anaerobic capacity in college taekwondo players.
METHODS
A total of 30 taekwondo players completed an 8-week training intervention with autoregulatory progressive resistance exercise (APRE; = 15) and velocity-based resistance training (VBRT; = 15). Testing included the one-repetition maximum squat, countermovement jump (CMJ), taekwondo anaerobic intermittent kick test (TAIKT), and 30-s Wingate anaerobic test (WAnT).
RESULTS
(1) Intragroup comparisons revealed significant effects for one-repetition maximum squat, peak power of CMJ (CMJ), relative peak power of CMJ (CMJ), and total number of TAIKT (TAIKT) in both the APRE and VBRT groups. The VBRT group exhibited small effect sizes for time at peak power of WAnT (WAnT) and moderate effect sizes for peak power of WAnT (WAnT), relative peak power of WAnT (WAnT), and fatigue index of TAIKT (TAIKT), whereas the APRE group exhibited small effect sizes for TAIKT. (2) Intergroup comparisons revealed no significant effects in any of the results. However, VBRT demonstrated a moderate advantage in WAnT and WAnT, whereas APRE had a small advantage in CMJ and CMJ.
CONCLUSIONS
These findings suggest that APRE improved explosive power (CMJ and CMJ) more, whereas VBRT improved anaerobic power output (WAnT and WAnT) more. Both methods were found to have similar effects in improving the anaerobic endurance (WAnT and TAIKT) and fatigue index (power drop of WAnT and TAIKT).
PubMed: 38464602
DOI: 10.1016/j.jesf.2024.02.005 -
Scientific Reports Mar 2024Identifying disease predictors through advanced statistical models enables the discovery of treatment targets for schizophrenia. In this study, a multifaceted clinical...
Identifying disease predictors through advanced statistical models enables the discovery of treatment targets for schizophrenia. In this study, a multifaceted clinical and laboratory analysis was conducted, incorporating magnetic resonance spectroscopy with immunology markers, psychiatric scores, and biochemical data, on a cohort of 45 patients diagnosed with schizophrenia and 51 healthy controls. The aim was to delineate predictive markers for diagnosing schizophrenia. A logistic regression model was used, as utilized to analyze the impact of multivariate variables on the prevalence of schizophrenia. Utilization of a stepwise algorithm yielded a final model, optimized using Akaike's information criterion and a logit link function, which incorporated eight predictors (White Blood Cells, Reactive Lymphocytes, Red Blood Cells, Glucose, Insulin, Beck Depression score, Brain Taurine, Creatine and Phosphocreatine concentration). No single factor can reliably differentiate between healthy patients and those with schizophrenia. Therefore, it is valuable to simultaneously consider the values of multiple factors and classify patients using a multivariate model.
Topics: Humans; Schizophrenia; Creatine; Phosphocreatine; Magnetic Resonance Spectroscopy; Brain
PubMed: 38459093
DOI: 10.1038/s41598-024-56344-3 -
Scientific Reports Mar 2024Emerging evidence implicates chronic psychological stress as a risk factor for Alzheimer's disease (AD). Herein, we examined the relationships between serum cortisol and...
Emerging evidence implicates chronic psychological stress as a risk factor for Alzheimer's disease (AD). Herein, we examined the relationships between serum cortisol and multimodality brain AD biomarkers in 277 cognitively normal midlife individuals at risk for AD. Overall, higher cortisol was associated with lower total brain volume, lower glucose metabolism (CMRglc) in frontal cortex, and higher β-amyloid (Aβ) load in AD-vulnerable regions; and marginally associated with phosphocreatine to ATP ratios (PCr/ATP) in precuneus and parietal regions. Sex-specific modification effects were noted: in women, cortisol exhibited stronger associations with Aβ load and frontal CMRglc, the latter being more pronounced postmenopause. In men, cortisol exhibited stronger associations with gray matter volume and PCr/ATP measures. Higher cortisol was associated with poorer delayed memory in men but not in women. Results were adjusted for age, Apolipoprotein E (APOE) epsilon 4 status, midlife health factors, and hormone therapy use. These results suggest sex-specific neurophysiological responses to stress, and support a role for stress reduction in AD prevention.
Topics: Male; Female; Humans; Hydrocortisone; Alzheimer Disease; Brain; Apolipoprotein E4; Biomarkers; Memory Disorders; Adenosine Triphosphate
PubMed: 38448497
DOI: 10.1038/s41598-024-56071-9