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Seminars in Respiratory and Critical... Oct 2023This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion,...
This article provides an overview of the journey of inspired oxygen after its uptake across the alveolar-capillary interface, and the interplay among tissue perfusion, diffusion, and cellular respiration in the transport and utilization of oxygen. The critical interactions between oxygen and its facilitative carriers (hemoglobin in red blood cells and myoglobin in muscle cells), and with other respiratory and vasoactive molecules (carbon dioxide, nitric oxide, and carbon monoxide), are emphasized to illustrate how this versatile system dynamically optimizes regional convective transport and diffusive gas exchange. The rates of reciprocal gas exchange in the lung and the periphery must be well-matched and sufficient for meeting the range of energy demands from rest to maximal stress but not excessive as to become toxic. The mobile red blood cells play a vital role in matching tissue perfusion and gas exchange by dynamically regulating the controlled uptake of oxygen and communicating regional metabolic signals across different organs. Intracellular oxygen diffusion and facilitation via myoglobin into the mitochondria, and utilization via electron transport chain and oxidative phosphorylation, are summarized. Physiological and pathophysiological adaptations are briefly described. Dysfunction of any component across this integrated system affects all other components and elicits corresponding structural and functional adaptation aimed at matching the capacities across the entire system and restoring equilibrium under normal and pathological conditions.
Topics: Humans; Oxygen; Myoglobin; Lung; Cell Respiration; Perfusion; Oxygen Consumption
PubMed: 37541315
DOI: 10.1055/s-0043-1770061 -
Endocrine, Metabolic & Immune Disorders... 2024Sarcopenia is becoming prevalent in older or inactive patients, which is placing a heavy burden on the social health system. Studies on the pathogenesis of sarcopenia...
Sarcopenia is becoming prevalent in older or inactive patients, which is placing a heavy burden on the social health system. Studies on the pathogenesis of sarcopenia mainly focus on adipose tissue, myoglobin autophagy, and mitochondrial dysfunction. Up to now, non-drug treatment has been the main way to treat sarcopenia, and there are no drugs specially approved for the treatment of sarcopenia. Here, the pathophysiology and treatment methods of sarcopenia have been summarized, and new drugs for sarcopenia to be researched and developed in the future have been prospected.
Topics: Humans; Aged; Sarcopenia; Aging; Autophagy; Muscle, Skeletal
PubMed: 37202891
DOI: 10.2174/1871530323666230518105408 -
Analytical Methods : Advancing Methods... Aug 2023Lateral flow assays (LFAs) have emerged as one of the most prominent paper-based biosensor platforms for rapidly detecting and quantifying analytes. Their selectivity,... (Review)
Review
Lateral flow assays (LFAs) have emerged as one of the most prominent paper-based biosensor platforms for rapidly detecting and quantifying analytes. Their selectivity, cost-effectiveness, efficiency, and simplicity make them ideal candidates for point-of-care (POC) applications, particularly when time-sensitive decisions are needed, such as cardiovascular events. The profound impact of cardiovascular diseases (CVDs), characterized by their high morbidity, mortality, and rehospitalization rates, necessitates an optimized approach for the early detection of cardiac muscle damage. This comprehensive review aims to consolidate the existing scientific literature on LFAs that specifically target cardiovascular biomarkers, including myoglobin and cardiac troponin I, over the past decade. By examining the advancements and findings in this field, valuable insights can be gained regarding the potential and future directions of LFAs in cardiovascular diagnostics.
Topics: Humans; Point-of-Care Systems; Biomarkers; Troponin I; Cardiovascular Diseases
PubMed: 37489903
DOI: 10.1039/d3ay01081c -
International Journal of Environmental... Nov 2023High-intensity interval training (HIIT) is considered an effective method to improve fitness and health indicators, but its high-intensity exercises and the mechanical... (Review)
Review
High-intensity interval training (HIIT) is considered an effective method to improve fitness and health indicators, but its high-intensity exercises and the mechanical and metabolic stress generated during the session can lead to the occurrence of exercise-induced muscle damage. Therefore, this study aimed to describe, by means of a systematic review, the effects of a single HIIT session on exercise-induced muscle damage. A total of 43 studies were found in the Medline/PubMed Science Direct/Embase/Scielo/CINAHL/LILACS databases; however, after applying the exclusion criteria, only 15 articles were considered eligible for this review. The total sample was 315 participants. Among them, 77.2% were men, 13.3% were women and 9.5 uninformed. Their age ranged from 20.1 ± 2 to 47.8 ± 7.5 years. HIIT protocols included running with ergometers (n = 6), CrossFit-specific exercises (n = 2), running without ergometers (n = 3), swimming (n = 1), the Wingate test on stationary bicycles (n = 2), and cycling (n = 1). The most applied intensity controls were %vVOmax, "all out", MV, MAV, Vmax, and HRreserve%. The most used markers to evaluate muscle damage were creatine kinase, myoglobin, and lactate dehydrogenase. The time for muscle damage assessment ranged from immediately post exercise to seven days. HIIT protocols were able to promote changes in markers of exercise-induced muscle damage, evidenced by increases in CK, Mb, LDH, AST, ALT, pain, and muscle circumference observed mainly immediately and 24 h after the HIIT session.
Topics: Male; Humans; Female; Exercise; Running; Exercise Therapy; High-Intensity Interval Training; Muscles
PubMed: 37998313
DOI: 10.3390/ijerph20227082 -
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 -
IScience Mar 2024The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin...
The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation. Mechanistically, the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, resulting in phosphorylation and inactivation of yes-associated protein (YAP). , myoglobin-deficient zebrafish hearts show YAP dephosphorylation and accelerated cardiac regeneration after apical injury. Similarly, myoglobin knockdown in neonatal murine hearts shows increased YAP dephosphorylation and cardiomyocyte cycling. These data demonstrate a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation and highlight myoglobin as a potential target to enhance cardiac development and improve cardiac repair and regeneration.
PubMed: 38414852
DOI: 10.1016/j.isci.2024.109146 -
American Journal of Kidney Diseases :... May 2024Toxic nephropathies are a clinically common group of disorders characterized by toxin-induced renal injury that can affect the glomerulus, vasculature, or... (Review)
Review
Toxic nephropathies are a clinically common group of disorders characterized by toxin-induced renal injury that can affect the glomerulus, vasculature, or tubulointerstitium. Various endogenous (eg, myoglobin, hemoglobin, monoclonal light chains, and lysozymes) and exogenous toxins (eg, therapeutic drugs, herbal medications, heavy metals, radiocontrast, intoxicants, and environmental exposures) have been implicated. The kidney's primary role of metabolism and excretion of substances via glomerular filtration and tubular secretion increases its susceptibility to their adverse effects. The structure, dose, metabolic handling, and excretory pathway of the drug/toxin through the kidney determines its nephrotoxic risk. Patient characteristics that impact risk include genetic determinants of drug metabolism, transport and excretion, immune response genes, and comorbid conditions. Clinical manifestations depend on site and severity of renal injury. Toxin-induced tubulointerstitial injury often presents as a decline in renal function and/or solute transport defects and renal solute wasting. Injury is often reversible with limited toxin exposure; however, irreversible renal injury can occur with prolonged exposure. In this Core Curriculum, we will focus on discussing mechanisms of common toxin-induced tubulointerstitial renal injury and review their causes, clinical presentations, diagnosis, and management.
Topics: Humans; Nephritis, Interstitial
PubMed: 38243994
DOI: 10.1053/j.ajkd.2023.09.017 -
Technology and Health Care : Official... Jan 2024There is no specificity in the clinical presentation of hemophagocytic lymphohistiocytosis (HLH).
BACKGROUND
There is no specificity in the clinical presentation of hemophagocytic lymphohistiocytosis (HLH).
OBJECTIVE
To study some clinical, etiological, and prognostic features of HLH to improve the clinical understanding of the disease.
METHODS
Retrospective analysis of the clinical data of 125 patients with HLH admitted to our hospital from June 2015 to August 2021, including clinical characteristics, laboratory indicators, and survival period. Statistical analysis was performed from the overall group of study indicators, which included population, children, and adults.
RESULTS
In the whole population, sex, age, blood myoglobin, and NK cell ratio of M-HLH and non-M-HLH patients (P< 0.05), serum albumin, and direct bilirubin were independent correlates of M-HLH. In the pediatric group, age and the proportion of NK cells were significantly different between M-HLH and non-M-HLH patients (P< 0.05). Multivariate Logistic regression analysis showed that all factors were not significantly associated with M-HLH. The associated regression analysis showed that all factors were not significantly associated with M-HLH. ROC curve analysis showed that the best predictive value of NK cell percentage for M-HLH diagnosis in the overall population was 4.96% in the pediatric group and 4.96% in the adult group. The best predictive value for M-HLH diagnosis was 2.08%. The univariate analysis showed that platelet count, alanine aminotransferase, aspartate aminotransferase, serum albumin, direct bilirubin and indirect bilirubin affected prognosis; COX regression showed that none of these factors had a significant relationship. The overall median survival time was 20.7 months in the adult group, 44.3 months in non-M-HLH patients, and 7.73 months in M-HLH patients (p= 0.011); univariate analysis showed that platelet count and serum albumin level affected prognosis; COX regression results in serum albumin level was an independent risk factor for prognosis.
CONCLUSION
The survival rate of non-M-HLH was significantly better than that of M-HLH; the proportion of NK cells had predictive value for the diagnosis of M-HLH; in the general population, non-M-HLH was more likely to have abnormal liver function than M-HLH: lower platelet count and serum albumin level were associated with poor prognosis, and the lower the platelet count and serum albumin level, the worse the prognosis: in addition, adults with lower serum albumin levels are also associated with poor prognosis.
PubMed: 38427515
DOI: 10.3233/THC-231275 -
Biomedicine & Pharmacotherapy =... Dec 2023Rhabdomyolysis is a severe clinical syndrome associated to acute kidney injury (AKI) and chronic kidney disease (CKD). TWEAK/Fn14 signaling axis regulates renal...
BACKGROUND
Rhabdomyolysis is a severe clinical syndrome associated to acute kidney injury (AKI) and chronic kidney disease (CKD). TWEAK/Fn14 signaling axis regulates renal inflammation and tubular cell death. However, the functional role of TWEAK/Fn14 in rhabdomyolysis remains unknown.
METHODS
Rhabdomyolysis was induced in wild-type, TWEAK- and Fn14-deficient mice or mice treated with TWEAK blocking antibody. Renal injury, inflammation, fibrosis and cell death were assessed. Additionally, we performed in vivo and in vitro studies to explore the possible signalling pathways involved in Fn14 regulation.
FINDINGS
Fn14 renal expression was increased in mice with rhabdomyolysis, correlating with decline of renal function. Mechanistically, myoglobin (Mb) induced Fn14 expression via ERK and p38 pathway, whereas Nrf2 activation diminished Mb-mediated Fn14 upregulation in cultured renal cells. TWEAK or Fn14 genetic depletion ameliorated rhabdomyolysis-associated loss of renal function, histological damage, tubular cell death, inflammation, and expression of both tubular and endothelial injury markers. Deficiency of TWEAK or Fn14 also decreased long-term renal inflammation and fibrosis in mice with rhabdomyolysis. Finally, pharmacological treatment with a blocking TWEAK antibody diminished the expression of acute renal injury markers and cell death and lessened residual kidney fibrosis and chronic inflammation in rhabdomyolysis.
INTERPRETATION
TWEAK/Fn14 axis participates in the pathogenesis of rhabdomyolysis-AKI and subsequent AKI-CKD transition. Blockade of this signaling pathway may represent a promising therapeutic strategy for reducing rhabdomyolysis-mediated renal injury.
FUNDING
Spanish Ministry of Science and Innovation, ISCIII and Junta de Andalucía.
Topics: Animals; Mice; Acute Kidney Injury; Cytokine TWEAK; Fibrosis; Inflammation; Renal Insufficiency, Chronic; Rhabdomyolysis; Tumor Necrosis Factors; TWEAK Receptor
PubMed: 38007933
DOI: 10.1016/j.biopha.2023.115925 -
3 Biotech Dec 2023Heme enzymes are the most prominent category of iron-containing metalloenzymes with the capability of catalyzing an astonishingly wide range of reactions like... (Review)
Review
Heme enzymes are the most prominent category of iron-containing metalloenzymes with the capability of catalyzing an astonishingly wide range of reactions like epoxidation, hydroxylation, demethylation, desaturation, reduction, sulfoxidation, and decarboxylation. Various enzymes in this category are P450s, heme peroxidases, catalases, myoglobin, cytochrome C, and others. Besides this, the natural promiscuity and amenability of these enzymes to protein engineering and evolution have also added several non-native reactions such as C-H, N-H, S-H insertions, cyclopropanation, and other industrially important reactions to their capabilities. Surprisingly, all of these reactions and their wide substrate scopes are attributed to changes in the active site scaffold of different heme enzymes as the center of all enzymes is constituted by a porphyrin ring containing iron. Multiple prominent research groups across the world, including 2018, Nobel Laureate Frances Arnold's group, have shown keen interest in engineering and evolving these enzymes for utilizing their industrial potential. Besides engineering the active site, researchers have also explored the possibility of these enzymes catalyzing non-native reactions by replacing the center porphyrin ring with other cofactors or by changing the iron in the porphyrin ring with other metal ions along with engineering the active site and thereby creating novel artificial metalloenzymes. Thus, in this mini-review from our group, for the first time, we are trying to catalog various activities catalyzed by heme enzymes and their engineered variants and their active usage in various industries along with shedding light on their potential for use in various applications in the future.
PubMed: 37942054
DOI: 10.1007/s13205-023-03804-8