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Nature Communications Oct 2023Gadolinium (Gd)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient...
Gadolinium (Gd)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given to using nanovesicles to improve its efficacy. Herein, Gd-Tex is transformed into building blocks "Gd-Tex-lipids" to self-assemble nanovesicles called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of Gd-Tex in a single nanovesicle and achieving high Gd-Tex accumulation in tumors. To elucidate the impact of O concentration on Gd-Tex radiosensitization, myoglobin (Mb) is loaded into Gd-NTs (Mb@Gd-NTs), resulting in efficient relief of tumor hypoxia and significant enhancement of Gd-Tex radiosensitization, eventually inducing the obvious long-term antitumor immune memory to inhibit tumor recurrence. In addition to Gd, the versatile Mb@Gd-NTs can also chelate Lu (Mb@Lu/Gd-NTs), enabling SPECT/MRI dual-modality imaging for accurately monitoring drug delivery in real-time. This "one-for-all" nanoplatform with the capability of chelating various trivalent metal ions exhibits broad clinical application prospects in imaging-guided radiosensitization therapy.
Topics: Humans; Gadolinium; Myoglobin; Oxygen; Radiation-Sensitizing Agents; Neoplasms; Magnetic Resonance Imaging
PubMed: 37794000
DOI: 10.1038/s41467-023-41782-w -
PeerJ 2022The study aimed to evaluate changes in selected biochemical indicators among mixed martial arts competitors in subsequent periods of the training cycle. The research...
The study aimed to evaluate changes in selected biochemical indicators among mixed martial arts competitors in subsequent periods of the training cycle. The research involved 12 mixed martial arts athletes aged 25.8 ± 4.2 years competing in the intermediate category. Selected somatic indicators were measured twice. Biochemical indicators were assessed five times during the 14-week study period. Serum concentrations of testosterone, cortisol, uric acid, myoglobin, total protein, interleukin 6, and tumor necrosis factor, as well as creatine kinase activity were determined. One hour after sparring completion, there were significant increases in cortisol (by 54.9%), uric acid (22.0%), myoglobin (565.0%), and interleukin 6 (280.3%) as compared with the values before the simulated fight. The highest creatine kinase activity (893.83 ± 139.31 U/l), as well as tumor necrosis factor (3.93 ± 0.71 pg/ml) and testosterone (5.83 ± 0.81 ng/ml) concentrations ( = 0.00) were recorded 24 hours after the simulation. Systematic observation of selected blood biochemical indicators in the training process periodization in mixed martial arts helps understand adaptive, compensatory, and regenerative mechanisms occurring in training athletes.
Topics: Humans; Hydrocortisone; Interleukin-6; Myoglobin; Uric Acid; Martial Arts; Testosterone; Athletes; Tumor Necrosis Factor-alpha; Creatine Kinase
PubMed: 35047233
DOI: 10.7717/peerj.12708 -
Molecular Aspects of Medicine Apr 2022Antonini and Brunori's 1971 book "Hemoglobin and Myoglobin in Their Reactions with Ligands" was a truly remarkable publication that summarized almost 100 years of... (Review)
Review
Antonini and Brunori's 1971 book "Hemoglobin and Myoglobin in Their Reactions with Ligands" was a truly remarkable publication that summarized almost 100 years of research on O binding to these globins. Over the ensuing 50 years, ultra-fast laser photolysis techniques, high-resolution and time resolved X-ray crystallography, molecular dynamics simulations, and libraries of recombinant myoglobin (Mb) and hemoglobin (Hb) variants have provided structural interpretations of O binding to these proteins. The resultant mechanisms provide quantitative descriptions of the stereochemical factors that govern overall affinity, including proximal and distal steric restrictions that affect iron reactivity and favorable positive electrostatic interactions that preferentially stabilize bound O. The pathway for O uptake and release by Mb and subunits of Hb has been mapped by screening libraries of site-directed mutants in laser photolysis experiments. O enters mammalian Mb and the α and β subunits of human HbA through a channel created by upward and outward rotation of the distal His at the E7 helical position, is non-covalently captured in the interior of the distal cavity, and then internally forms a bond with the heme Fe(II) atom. O dissociation is governed by disruption of hydrogen bonding interactions with His (E7), breakage of the Fe(II)-O bond, and then competition between rebinding and escape through the E7-gate. The structural features that govern the rates of both the individual steps and overall reactions have been determined and provide the framework for: (1) defining the physiological functions of specific globins and their evolution; (2) understanding the clinical features of hemoglobinopathies; and (3) designing safer and more efficient acellular hemoglobin-based oxygen carriers (HBOCs) for transfusion therapy, organ preservation, and other commercially relevant O transport and storage processes.
Topics: Animals; Carbon Monoxide; Hemoglobins; Humans; Kinetics; Ligands; Mammals; Myoglobin; Oxygen
PubMed: 34544605
DOI: 10.1016/j.mam.2021.101024 -
Medicina Clinica Aug 2021The outbreak of novel coronavirus pneumonia 2019 (COVID-19) has caused millions of deaths worldwide. It is well documented that troponin predicts the prognosis of...
BACKGROUND
The outbreak of novel coronavirus pneumonia 2019 (COVID-19) has caused millions of deaths worldwide. It is well documented that troponin predicts the prognosis of patients. Myoglobin is not only an important marker of myocardial injury, but it indicates systemic muscle damage. However, its relationship with COVID-19 was rarely reported. The present study compared the predictive value of troponin and myoglobin on the final prognosis of COVID-19 patients by analyzing the clinical characteristics and serum levels of myoglobin and troponin in severe/critical COVID-19 patients.
METHODS
We enrolled 499 consecutive eligible hospitalized patients with severe/critical COVID-19 from February 14 to March 24, 2020 at Leishenshan Hospital, Wuhan, China. Clinical characteristics and laboratory data were collected and compared between the patients who died and survived. We analyzed the receiver operating characteristic curves of myoglobin and troponin. Then, the patients were divided into myo group, myo group, tro group, and tro group, and survival curves were analyzed. The prognostic predictable values of myoglobin and troponin were further analyzed using Cox multifactorial analysis.
RESULTS
Myoglobin and troponin were significantly elevated in the death group (134.4 [interquartile range (IQR) 24.80, 605] vs 38.02 [IQR 3.87, 11.73]ng/ml, p<0.001), and troponin was also significantly elevated in the death group (0.01 [IQR 0.01, 0.01] vs 0.04 [IQR 0.02, 0.15]ng/ml, p<0.001). The ROC curves demonstrated that the area under the curve when using myoglobin to predict patient death was 0.911, with a threshold of 1.17, which was equivalent to troponin. Kaplan-Meier survival analysis revealed a significantly lower survival curve in the myo group than the myo group. Multifactor Cox survival analysis showed that troponin was no longer significant (HR=0.98, 95% CI 0.92-1.03, p=0.507), but elevated myoglobin was an independent predictor of death in COVID-19 patients (HR=1.001, 95% CI 1.001-1.002, p<0.001). The analysis of the Cox model for predicting patient death and plotting decision curves suggested that the single factor myoglobin model was superior to troponin, and the predictive value of the multifactor model was superior to the single-factor analyses.
CONCLUSIONS
In severe/critical COVID-19 patients, myoglobin and troponin were predictors of mortality and the probability of conversion to critical illness, and myoglobin may be superior to troponin for predictive value.
Topics: Biomarkers; COVID-19; Humans; Myoglobin; Prognosis; Retrospective Studies; SARS-CoV-2; Troponin
PubMed: 33958143
DOI: 10.1016/j.medcli.2021.01.013 -
International Journal of Molecular... Jun 2017Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to... (Review)
Review
Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to sulfate while hydrogen sulfide is transformed into thiosulfate. These processes occurring mostly in mitochondria are described as a canonical hydrogen sulfide oxidation pathway. In this review, we discuss the current state of knowledge on the interactions between hydrogen sulfide and hemoglobin, myoglobin and neuroglobin and postulate that thiosulfate is a metabolically important product of this processes. Hydrogen sulfide oxidation by ferric hemoglobin, myoglobin and neuroglobin has been defined as a non-canonical hydrogen sulfide oxidation pathway. Until recently, it appeared that the goal of thiosulfate production was to delay irreversible oxidation of hydrogen sulfide to sulfate excreted in urine; while thiosulfate itself was only an intermediate, transient metabolite on the hydrogen sulfide oxidation pathway. In the light of data presented in this paper, it seems that thiosulfate is a molecule that plays a prominent role in the human body. Thus, we hope that all these findings will encourage further studies on the role of hemoproteins in the formation of this undoubtedly fascinating molecule and on the mechanisms responsible for its biological activity in the human body.
Topics: Cysteine; Globins; Hemeproteins; Hemoglobins; Humans; Hydrogen Sulfide; Mitochondria; Myoglobin; Nerve Tissue Proteins; Neuroglobin; Oxidation-Reduction; Sulfides; Sulfites; Thiosulfates
PubMed: 28632164
DOI: 10.3390/ijms18061315 -
Archives of Pathology & Laboratory... Nov 2019Urine myoglobin testing is primarily indicated for diagnosis and risk assessment of kidney injury in patients with rhabdomyolysis. However, its utility is limited by a... (Observational Study)
Observational Study
CONTEXT.—
Urine myoglobin testing is primarily indicated for diagnosis and risk assessment of kidney injury in patients with rhabdomyolysis. However, its utility is limited by a lack of rapid and reliable results. Myoglobin reacts positively for blood by urine dipstick, which can serve as an indicator of myoglobinuria.
OBJECTIVE.—
To evaluate the performance and value of blood and red cell measurements by urinalysis as a surrogate test for myoglobinuria in routine clinical practice.
DESIGN.—
This study is a retrospective observational study involving analysis of hemoglobin and red blood cell results by urinalysis in patients tested for urine myoglobin.
RESULTS.—
A total of 13 139 urine myoglobin results from 88 Veterans Affairs facilities during a 15-year period ending in October 2014 were evaluated. Among methods used by each laboratory, qualitative urine myoglobin tests declined from 25 of 53 (47.1%) in 2000 to 5 of 77 (6.4%) in 2013. Of 7311 tests (55.6%) performed by quantitative methods with concomitant urinalysis, 3915 (53.5%) showed negative to trace blood results, of which myoglobin was 1000 μg/L or greater in 17 (0.4%). Among 1875 (25.5%) with 3+ (large) blood results, urine myoglobin was ≥1000 μg/L in 273 of 1533 (17.8%) with hematuria (≥5 red blood cells per microliter) and 109 of 342 (31.9%) without hematuria.
CONCLUSIONS.—
Urinalysis results reliably predicted the absence of myoglobinuria and could be used to avert overtesting for urine myoglobin while also providing useful diagnostic information when urine myoglobin test results are not immediately available.
Topics: Evidence-Based Practice; Hematuria; Hemoglobins; Humans; Myoglobin; Myoglobinuria; Retrospective Studies; Rhabdomyolysis; United States; United States Department of Veterans Affairs; Urinalysis
PubMed: 31116043
DOI: 10.5858/arpa.2018-0475-OA -
The Journal of Biological Chemistry 2021Proteins are the molecular machines of living systems. Their dynamics are an intrinsic part of their evolutionary selection in carrying out their biological functions.... (Review)
Review
Proteins are the molecular machines of living systems. Their dynamics are an intrinsic part of their evolutionary selection in carrying out their biological functions. Although the dynamics are more difficult to observe than a static, average structure, we are beginning to observe these dynamics and form sound mechanistic connections between structure, dynamics, and function. This progress is highlighted in case studies from myoglobin and adenylate kinase to the ribosome and molecular motors where these molecules are being probed with a multitude of techniques across many timescales. New approaches to time-resolved crystallography are allowing simple "movies" to be taken of proteins in action, and new methods of mapping the variations in cryo-electron microscopy are emerging to reveal a more complete description of life's machines. The results of these new methods are aided in their dissemination by continual improvements in curation and distribution by the Protein Data Bank and their partners around the world.
Topics: Adenylate Kinase; Animals; Databases, Protein; Humans; Models, Molecular; Myoglobin; Ribosomes; Structure-Activity Relationship
PubMed: 33961840
DOI: 10.1016/j.jbc.2021.100749 -
Anais Da Academia Brasileira de Ciencias 2024Intensive Care Unit-acquired weakness (ICU-AW) is a common complication that significantly impedes patient recovery. In the study, we investigated the correlation... (Comparative Study)
Comparative Study
Correlation Between Early Serum Myoglobin Levels and the Incidence and Prognosis of Intensive Care Unit-Acquired Weakness (ICU-AW) in Septic Shock Patients: A Comparative Study.
Intensive Care Unit-acquired weakness (ICU-AW) is a common complication that significantly impedes patient recovery. In the study, we investigated the correlation between early serum myoglobin levels in patients with septic shock due to pneumonia, and the incidence of ICU-AW, duration of mechanical ventilation, and prognosis. Patients were classified based on the development of ICU-AW within the first 10 days of ICU admission. We measured serum myoglobin levels upon ICU entry, and analyzed demographic data, APACHE II scores, use of mechanical ventilation, and clinical outcomes, including mortality and duration of mechanical ventilation. The results indicated significantly elevated serum myoglobin levels in the ICU-AW group, correlated with prolonged mechanical ventilation and increased mortality. ROC analysis revealed myoglobin as a promising biomarker for predicting ICU-AW, with an area under the curve of 0.843 (95% CI: 0.819~0.867), demonstrating a sensitivity of 76.00% and specificity of 82.30%. These findings underscored serum myoglobin as a predictive biomarker for early ICU-AW in septic shock patients, highlighting its potential to guide clinical decision-making.
Topics: Humans; Shock, Septic; Myoglobin; Male; Intensive Care Units; Female; Middle Aged; Biomarkers; Prognosis; Muscle Weakness; Aged; Incidence; Respiration, Artificial; APACHE; ROC Curve
PubMed: 38747799
DOI: 10.1590/0001-3765202420231164 -
Physiological Reports May 2021Myoglobin is an important regulator of muscle and whole-body metabolism and exercise capacity. Caffeine, an activator of the calcium and cyclic AMP (cAMP)/protein kinase...
Myoglobin is an important regulator of muscle and whole-body metabolism and exercise capacity. Caffeine, an activator of the calcium and cyclic AMP (cAMP)/protein kinase A (PKA) pathway, enhances glucose uptake, fat oxidation, and mitochondrial biogenesis in skeletal muscle cells. However, no study has shown that caffeine increases the endogenous expression of myoglobin in muscle cells. Further, the molecular mechanism underlying the regulation of myoglobin expression remains unclear. Therefore, our aim was to investigate whether caffeine and activators of the calcium signaling and cAMP/PKA pathway increase the expression of myoglobin in L6 myotubes and whether the pathway mediates caffeine-induced myoglobin expression. Caffeine increased myoglobin expression and activated the cAMP/PKA pathway in L6 muscle cells. Additionally, a cAMP analog significantly increased myoglobin expression, whereas a ryanodine receptor agonist showed no significant effect. Finally, PKA inhibition significantly suppressed caffeine-induced myoglobin expression in L6 myotubes. These results suggest that caffeine increases myoglobin expression via the cAMP/PKA pathway in skeletal muscle cells.
Topics: Animals; Caffeine; Cell Line; Central Nervous System Stimulants; Cyclic AMP; Muscle Fibers, Skeletal; Myoglobin; Rats
PubMed: 33991466
DOI: 10.14814/phy2.14869 -
Archives of Biochemistry and Biophysics Jul 2020Hydropersulfides are reported to be good biological reductants, superior to thiols and akin to selenols. As such, they have been previously shown to reduce...
Hydropersulfides are reported to be good biological reductants, superior to thiols and akin to selenols. As such, they have been previously shown to reduce metalloproteins such as ferric myoglobin and ferric cytochrome c to their ferrous forms under conditions where little or no reduction from corresponding thiols is observed. Not surprisingly, the reduction of ferric myoglobin to ferrous myoglobin under aerobic conditions results in the generation of oxymyoglobin (dioxygen bound ferrous myoglobin). Previous studies have demonstrated that oxymyoglobin can also act as an oxidant with highly reducing species such as hydroxylamine and ascorbate. Considering the reducing properties of hydropersulfides, it is possible that they can also react with oxymyoglobin similarly to hydroxylamine or ascorbate. Herein, this reaction is examined and indeed hydropersulfides are found to react with oxymyoglobin similarly to other reducing species leading to a fleeting ferric myoglobin which is rapidly reduced to the ferrous form also by hydropersulfide.
Topics: Animals; Ascorbic Acid; Cattle; Horses; Hydroxylamine; Models, Chemical; Myoglobin; Oxidation-Reduction; Oxygen; Penicillamine; Sulfides
PubMed: 32360749
DOI: 10.1016/j.abb.2020.108391