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The Journal of Physical Chemistry. B May 2024The disaccharide trehalose is generally acknowledged as a superior stabilizer of proteins and other biomolecules in aqueous environments. Despite many theories aiming to... (Comparative Study)
Comparative Study
The disaccharide trehalose is generally acknowledged as a superior stabilizer of proteins and other biomolecules in aqueous environments. Despite many theories aiming to explain this, the stabilization mechanism is still far from being fully understood. This study compares the stabilizing properties of trehalose with those of the structurally similar disaccharide sucrose. The stability has been evaluated for the two proteins, lysozyme and myoglobin, at both low and high temperatures by determining the glass transition temperature, , and the denaturation temperature, . The results show that the sucrose-containing samples exhibit higher than the corresponding trehalose-containing samples, particularly at low water contents. The better stabilizing effect of sucrose at high temperatures may be explained by the fact that sucrose, to a greater extent, binds directly to the protein surface compared to trehalose. Both sugars show elevation with an increasing sugar-to-protein ratio, which allows for a more complete sugar shell around the protein molecules. Finally, no synergistic effects were found by combining trehalose and sucrose. Conclusively, the exact mechanism of protein stabilization may vary with the temperature, as influenced by temperature-dependent interactions between the protein, sugar, and water. This variability can make trehalose to a superior stabilizer under some conditions and sucrose under others.
Topics: Trehalose; Sucrose; Muramidase; Calorimetry, Differential Scanning; Myoglobin; Protein Stability; Animals; Temperature
PubMed: 38733344
DOI: 10.1021/acs.jpcb.4c00022 -
International Journal of Molecular... Apr 2024Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of...
Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of hemoglobin (HMG) and myoglobin (MGB) blockade by hydrochloric acid (HCl) in an interaction model with gaseous anesthetics using molecular docking techniques. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand-receptor complexes to investigate the stability of the ligand-receptor complexes and the interactions between ligands and receptors in more detail. Through docking analysis, we observed that hemoglobin creates more stable complexes with anesthetic gases than myoglobin. Intoxication with gaseous hydrochloric acid produces conformational and binding energy changes of anesthetic gases to the substrate (both the pathway and the binding site), the most significant being recorded in the case of desflurane and sevoflurane, while for halothane and isoflurane, they remain unchanged. According to our theoretical model, the selection of anesthetic agents for patients affected by fire smoke containing hydrochloric acid is critical to ensure optimal anesthetic effects. In this regard, our model suggests that halothane and isoflurane are the most suitable choices for predicting the anesthetic effects in such patients when compared to sevoflurane and desflurane.
Topics: Humans; Molecular Dynamics Simulation; Anesthesia, General; Molecular Docking Simulation; Myoglobin; Hydrochloric Acid; Smoke; Anesthetics, Inhalation; Hemoglobins; Halothane; Binding Sites
PubMed: 38731919
DOI: 10.3390/ijms25094701 -
International Journal of Molecular... Apr 2024This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia...
This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium's response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes.
Topics: Humans; Male; Hypoxia; Biomarkers; Pilot Projects; Athletes; Swimming; Young Adult; Myocardium; Myoglobin; Troponin I; Fatty Acid Binding Protein 3; Adolescent; Fatty Acid-Binding Proteins; Physical Endurance; Creatine Kinase, MB Form; Adaptation, Physiological; Altitude
PubMed: 38731803
DOI: 10.3390/ijms25094584 -
American Journal of Translational... 2024To explore the predictive utility of serum myoglobin (Mb) and lactate dehydrogenase (LDH) for acute kidney injury (AKI) secondary to rhabdomyolysis (RM) in severe...
OBJECTIVE
To explore the predictive utility of serum myoglobin (Mb) and lactate dehydrogenase (LDH) for acute kidney injury (AKI) secondary to rhabdomyolysis (RM) in severe heatstroke patients.
METHODS
A retrospective analysis of 58 RM patients with severe heatstroke at Shanghai Ninth People's Hospital from June 2019 to May 2022 was conducted. Patients were categorized into AKI and non-AKI groups. Laboratory indices were compared, and receiver operating characteristic (ROC) curves were used to assess the predictive value of serum biomarkers for AKI.
RESULTS
Creatine kinase, Mb, LDH, creatinine, and blood urea nitrogen levels were significantly higher in the AKI group (P<0.05). Serum Mb and LDH were positively correlated with serum creatinine (r=0.6772 and r=0.6816, respectively; P<0.05). The area under the ROC curve (AUC) for serum Mb was 0.6692 (95% CI: 0.5253-0.8131) with a cut-off of 1024 ng/ml, while for LDH it was 0.8277 (95% CI: 0.7182-0.9371) with a cut-off of 1342 U/L. Combining serum Mb and LDH improved the AUC to 0.9116 (95% CI: 0.8219-1.001).
CONCLUSION
Serum Mb and LDH levels are elevated in RM-induced AKI following severe heatstroke, and their combination offers substantial predictive value for AKI in these patients.
PubMed: 38715805
DOI: 10.62347/QSRI4858 -
Data in Brief Jun 2024Cancer cells influence their microenvironment by secreting factors that promote tumour growth and survival while evading immune-mediated destruction. We previously...
Cancer cells influence their microenvironment by secreting factors that promote tumour growth and survival while evading immune-mediated destruction. We previously determined the expression of secreted factors in breast and oesophageal squamous cell carcinoma cell lines (MCF-7 and WHCO6, respectively) using Luminex assays. These cells were subsequently treated with low pH medium to mimic acid exposure, and the effects on cell viability, proliferation, and secretion of cytokines, chemokines and growth factors were described [1]. Here, we present the datasets from these experiments in addition to data obtained from treating cell lines with conditioned medium from apoptotic cell cultures.
PubMed: 38711735
DOI: 10.1016/j.dib.2024.110460 -
Frontiers in Cardiovascular Medicine 2024Postoperative acute kidney injury (PO-AKI) is a prevalent complication among patients with acute type A aortic dissection (aTAAD) for which unrecognized trajectories of...
BACKGROUND
Postoperative acute kidney injury (PO-AKI) is a prevalent complication among patients with acute type A aortic dissection (aTAAD) for which unrecognized trajectories of renal function recovery, and their heterogeneity, may underpin poor success in identifying effective therapies.
METHODS
This was a retrospective, single-center cohort study in a regional Great Vessel Center including patients undergoing aortic dissection surgery. Estimated glomerular filtration rate (eGFR) recovery trajectories of PO-AKI were defined through the unsupervised latent class mixture modeling (LCMM), with an assessment of patient and procedural characteristics, complications, and early-term survival. Internal validation was performed by resampling.
RESULTS
A total of 1,295 aTAAD patients underwent surgery and 645 (49.8%) developed PO-AKI. Among the PO-AKI cohort, the LCMM identified two distinct eGFR trajectories: early recovery (ER-AKI, 51.8% of patients) and late or no recovery (LNR-AKI, 48.2% of patients). Binary logistic regression identified five critical determinants regarding poor renal recovery, including chronic kidney disease (CKD) history, renal hypoperfusion, circulation arrest time, intraoperative urine, and myoglobin. LNR-AKI was associated with increased mortality, continuous renal replacement therapies, mechanical ventilation, ICU stay, and hospital stay. The assessment of the predictive model was good, with an area under the curve (AUC) of 0.73 (95% CI: 0.69-0.76), sensitivity of 61.74%, and specificity of 75.15%. The internal validation derived a consistent average AUC of 0.73. The nomogram was constructed for clinicians' convenience.
CONCLUSION
Our study explored the PO-AKI recovery patterns among surgical aTAAD patients and identified critical determinants that help to predict individuals at risk of poor recovery of renal function.
PubMed: 38707890
DOI: 10.3389/fcvm.2024.1364332 -
Physiological Reviews May 2024A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O) storage protein supporting mitochondrial oxidative phosphorylation,... (Review)
Review
A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O partial pressure (O) drops and Mb offloads O. Besides O storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR) , and "ectopic" expression in some types of cancer cells and in brown adipose tissue (BAT). Data from Mb knockout (Mb) mice and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools, modulation of BAT bioenergetics, thermogenesis, and lipid storage phenotypes. From these and other findings in the literature over many decades, Mb's function is not confined to delivering O in support of oxidative phosphorylation, but also to serve as an O-sensor that modulates intracellular O- and NO-responsive molecular signaling pathways. This paradigm reflects a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Herein, we review historic and emerging views related to the physiological roles for Mb, and present working models illustrating the possible importance of interactions between Mb, gases, and small molecule metabolites in regulation of cell signaling and bioenergetics.
PubMed: 38696337
DOI: 10.1152/physrev.00031.2023 -
Cureus Apr 2024Rhabdomyolysis is characterised by muscle breakdown and the release of myoglobin. It is a potentially serious condition that can lead to acute kidney injury (AKI)....
Rhabdomyolysis is characterised by muscle breakdown and the release of myoglobin. It is a potentially serious condition that can lead to acute kidney injury (AKI). Factors, such as ischemia, trauma, muscle compression and drug toxicity, can trigger muscle breakdown. Treatment involves aggressive fluid resuscitation to maintain urine output and prevent renal injury. Severe cases with AKI may require temporary renal replacement therapy, such as haemodialysis. It has also been proposed that dialysis can speed up recovery by removing myoglobin that is secreted into the circulation by injured muscles. We present a case of a patient with alcohol abuse and prolonged immobility leading to severe rhabdomyolysis requiring hemodialysis. Our aim is to emphasise the importance of timely identification, and appropriate management of severe rhabdomyolysis not improving on fluids may require HD as soon as possible in order to minimise complications.
PubMed: 38694661
DOI: 10.7759/cureus.59316 -
Nefrologia Apr 2024New generation helixone dialyzers has recently been developed as part of the ongoing effort to improve dialyzer hemocompatibility and avoid adverse reactions to...
INTRODUCTION
New generation helixone dialyzers has recently been developed as part of the ongoing effort to improve dialyzer hemocompatibility and avoid adverse reactions to synthetic dialyzers. This study aimed to assess the performance and albumin loss of this new dialyzer series in hemodiafiltration and compare it with the previous generation helixone series.
MATERIAL AND METHODS
A prospective study was conducted in 19 patients. Each patient underwent eight dialysis sessions with the same routine dialysis parameters; only the dialyzer varied: FX60 CorDiax, FX CorAL 60, FX600 CorDiax, FX CorAL 600, FX80 CorDiax, FX CorAL 80, FX800 CorDiax, and FX CorAL 800. The reduction ratios (RR) of urea, creatinine, ß-microglobulin, myoglobin, kappa-free immunoglobulin light chains (κFLC), prolactin, α-microglobulin, α-acid glycoprotein, lambda immunoglobulin light chains (λFLC), and albumin were compared intra-individually. Dialysate albumin loss was also measured.
RESULTS
All treatments were well tolerated. The mean amount of replacement fluid ranged from 31 to 34 L. Comparison of dialysis treatments showed no differences between small molecules and even up to those the size of β2-microglobulins. Little differences were found between myoglobin, κFLC, prolactin, α-microglobulin, and λFLC RRs, and only FX80 CorDiax was slightly superior to the others. Mean dialysate albumin losses were similar, with less than 2.5 g lost in each dialyzer. The FX80 CorDiax showed slightly higher global removal scores than the other dialyzers evaluated, except for FX CorAL 800.
CONCLUSION
The new generation helixone dialyzers series has been updated to minimise the risk of adverse reactions, while maintaining the effectiveness and albumin loss achieved by the previous most advanced helixone generation.
PubMed: 38679516
DOI: 10.1016/j.nefroe.2024.04.005 -
Pharmaceutics Apr 2024Lipid-based nanocarriers have emerged as helpful tools to deliver sensible biomolecules such as proteins and oligonucleotides. To have a fast and robust...
Lipid-based nanocarriers have emerged as helpful tools to deliver sensible biomolecules such as proteins and oligonucleotides. To have a fast and robust microfluidic-based nanoparticle synthesis method, the setup of versatile equipment should allow for the rapid transfer to scale cost-effectively while ensuring tunable, precise and reproducible nanoparticle attributes. The present work aims to assess the effect of different micromixer geometries on the manufacturing of lipid nanocarriers taking into account the influence on the mixing efficiency by changing the fluid-fluid interface and indeed the mass transfer. Since the geometry of the adopted micromixer varies from those already published, a Design of Experiment (DoE) was necessary to identify the operating (total flow, flow rate ratio) and formulation (lipid concentration, lipid molar ratios) parameters affecting the nanocarrier quality. The suitable application of the platform was investigated by producing neutral, stealth and cationic liposomes, using DaunoXome, Myocet, Onivyde and Onpattro as the benchmark. The effect of condensing lipid (DOTAP, 3-10-20 mol%), coating lipids (DSPE-PEG550 and DSPE-PEG2000), as well as structural lipids (DSPC, eggPC) was pointed out. A very satisfactory encapsulation efficiency, always higher than 70%, was successfully obtained for model biomolecules (myoglobin, short and long nucleic acids).
PubMed: 38675169
DOI: 10.3390/pharmaceutics16040507