Dataset Information

Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology.

ABSTRACT:

Purpose of review

This review summarizes the significant biophysical and rheological aspects of red blood cell physiology and pathophysiology in relation to recent advances in microfluidic biomarker assays and emerging targeted or curative intent therapies.

Recent findings

Alterations in red cell biophysical properties and blood rheology have been associated with numerous hematologic and circulatory disorders. Recent advances in biomarker assays enable effective assessment of these biophysical and rheological properties in normoxia or physiological hypoxia in a clinically meaningful way. There are emerging targeted or curative therapies that aim to improve red cell pathophysiology, especially in the context of inherited hemoglobin disorders, such as sickle cell disease.

Summary

Red cell pathophysiology can be therapeutically targeted and the improvements in membrane and cellular biophysics and blood rheology can now be feasibly assessed via new microfluidic biomarker assays. Recent advances provide a new hope and novel treatment options for major red cell ailments, including inherited hemoglobin disorders, membrane disorders, and other pathologies of the red cell, such as malaria.

SUBMITTER: Gurkan UA

PROVIDER: S-EPMC8215585 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology.

Gurkan Umut A UA

Current opinion in hematology 20210501 3

<h4>Purpose of review</h4>This review summarizes the significant biophysical and rheological aspects of red blood cell physiology and pathophysiology in relation to recent advances in microfluidic biomarker assays and emerging targeted or curative intent therapies.<h4>Recent findings</h4>Alterations in red cell biophysical properties and blood rheology have been associated with numerous hematologic and circulatory disorders. Recent advances in biomarker assays enable effective assessment of thes ...[more]

PMID: 33631785

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Project description:BackgroundIon and metal homeostasis are critical to red blood cell physiology and Inductively Coupled Plasma (ICP) is a decades old approach to pursue elemental analysis. Recent evolution of ICP has resulted in its coupling to mass spectrometry (MS) instead of atomic absorption/emission.MethodsHere we performed Inductively-coupled plasma mass spectrometry (ICP-MS) measurements of intra- and extra-cellular Na, K, Ca, Mg, Fe, and Cu in red blood cells undergoing ionic, heat, or starvation stress. Results were correlated with Ca measurements from other common platforms (e.g., fluorescence-based approaches) and extensive measurements of red blood cell metabolism.ResultsAll stresses induced significant intra- and extracellular alterations of all measured elements. In particular, ionomycin treatment or hypertonic stress significantly impacted intracellular sodium and extracellular potassium and magnesium levels. Iron efflux was observed as a function of temperatures, with ionic and heat stress at 40°C causing the maximum decrease in intracellular iron pools and increases in the supernatants. Strong positive correlation was observed between calcium measurements via ICP-MS and fluorescence-based approaches. Correlation analyses with metabolomics data showed a strong positive association between extracellular calcium and intracellular sodium or magnesium levels and intracellular glycolysis. Extracellular potassium or iron were positively correlated with free fatty acids (especially mono-, poly-, and highly-unsaturated or odd-chain fatty acid products of lipid peroxidation). Intracellular iron was instead positively correlated with saturated fatty acids (palmitate, stearate) and negatively with methionine metabolism (methionine, S-adenosylmethionine), phosphatidylserine exposure and glycolysis.ConclusionIn the era of omics approaches, ICP-MS affords a comprehensive characterization of intracellular elements that provide direct insights on red blood cell physiology and represent meaningful covariates for data generated via other omics platforms such as metabolomics.

Project description:Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics.

Dataset Information

Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology.

Purpose of review

Recent findings

Summary

Publications

Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology.

Similar Datasets

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