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Cells Dec 2022The neonatal Fc receptor (FcRn) is highly expressed in the renal proximal tubule and is important for the reclamation of albumin by cellular transcytosis to prevent its...
The neonatal Fc receptor (FcRn) is highly expressed in the renal proximal tubule and is important for the reclamation of albumin by cellular transcytosis to prevent its loss in the urine. The initial event of this transcellular transport mechanism is the endocytosis of albumin by the apical scavenger receptors megalin and cubilin. An interaction of megalin and FcRn was postulated, however, evidence is still missing. Similarly, the intracellular trafficking of FcRn remains unknown and shall be identified in our study. Using a Venus-based bimolecular fluorescence complementation system, we detected an interaction between megalin and FcRn in the endosomal compartment, which significantly increased with the induction of endocytosis using albumin or lactoglobulin as a ligand. The interaction between megalin and FcRn occurred at a neutral and acidic pH between the extracellular domains of both proteins. Amnionless, another transmembrane acceptor of cubilin, revealed no interaction with FcRn. With the induction of endocytosis by albumin or lactoglobulin, super resolution microscopy demonstrated a redistribution of megalin and FcRn into clathrin vesicles and early endosomes. This trafficking into clathrin vesicles was impaired in megalin-deficient cells upon albumin-induced endocytosis, supporting the role of megalin in FcRn redistribution. Our results indicate that megalin and FcRn specifically bind and interact within their extracellular domains. The availability of megalin is necessary for the redistribution of FcRn. Megalin, therefore, orchestrates FcRn endocytosis and intracellular trafficking as an early event intranscytosis.
Topics: Albumins; Clathrin; Endocytosis; Ligands; Low Density Lipoprotein Receptor-Related Protein-2; Protein Transport
PubMed: 36611847
DOI: 10.3390/cells12010053 -
Acta Medica Portuguesa Mar 2023Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute... (Review)
Review
Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute heart failure are caused by congestive conditions, not all patients have a congestive phenotype, reflecting the complexity of a process with multiple pathophysiological pathways. The use of diuretics, usually loop diuretics, is the mainstay of treatment for congestion. However, many patients develop resistance, thus constituting a challenge with no consensual solution to date, despite extensive debate over the years. Despite its frequent use in clinical practice, the co-administration of albumin and furosemide remains controversial in the management of patients with acute heart failure, hypoalbuminemia, and diuretic resistance. This review addresses the pathophysiological mechanisms of congestion in patients with acute heart failure and explores the theoretical basis that supports the co-administration of albumin and furosemide in this clinical context. It is intended to clarify the potential benefit of the combined approach in this specific population and identify possible gaps in the literature that could be the subject of future studies.
Topics: Humans; Furosemide; Diuretics; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Albumins
PubMed: 36762993
DOI: 10.20344/amp.17714 -
Critical Care and Resuscitation :... Sep 2020Albumin is the most abundant and perhaps most important protein in human blood. Research has identified many of albumin's possible roles in modulating acid-base balance,... (Review)
Review
Albumin is the most abundant and perhaps most important protein in human blood. Research has identified many of albumin's possible roles in modulating acid-base balance, modifying inflammation, maintaining vascular endothelial integrity, and binding endogenous and exogenous compounds. Albumin plays a key role in the homeostasis of vascular endothelium, offering protection from inflammation and damage to the glycocalyx. Albumin binds a diverse range of compounds. It transports, delivers and clears drugs, plus it helps with uptake, storage and disposal of potentially harmful biological products. The biological effects of albumin in critical illness are incompletely understood, but may enhance its clinical role beyond use as an intravenous fluid. In this article, we summarise the evidence surrounding albumin's biological and physiological effects beyond its use for plasma volume expansion, and explore potential mechanistic effects of albumin as a disease modifier in patients with critical illness.
Topics: Albumins; Endothelial Cells; Endothelium, Vascular; Glycocalyx; Homeostasis; Humans
PubMed: 32900333
DOI: 10.1016/S1441-2772(23)00394-0 -
Biotechnology and Bioengineering Dec 2019Albumin, the most abundant plasma protein in mammals, is a versatile and easily obtainable biomaterial. It is pH and temperature responsive, dissolvable in high... (Review)
Review
Albumin, the most abundant plasma protein in mammals, is a versatile and easily obtainable biomaterial. It is pH and temperature responsive, dissolvable in high concentrations and gels readily in defined conditions. This versatility, together with its inexpensiveness and biocompatibility, makes albumin an attractive biomaterial for biomedical research and therapeutics. So far, clinical research in albumin has centered mainly on its use as a carrier molecule or nanoparticle to improve drug pharmacokinetics and delivery to target sites. In contrast, research in albumin-based hydrogels is less established albeit growing in interest over recent years. In this minireview, we report current literature and critically discuss the synthesis, mechanical properties, biological effects and uses, biodegradability and cost of albumin hydrogels as a xeno-free, customizable, and transplantable construct for tissue engineering and regenerative medicine.
Topics: Albumins; Animals; Cell Transplantation; Drug Carriers; Humans; Hydrogels; Nanoparticles; Regenerative Medicine
PubMed: 31520415
DOI: 10.1002/bit.27167 -
Nutrients Oct 2023Recently, there has been a growing focus on the prognostic significance of nutrition-related biomarkers. We attempted to explore the association between a novel...
BACKGROUND
Recently, there has been a growing focus on the prognostic significance of nutrition-related biomarkers. We attempted to explore the association between a novel albumin-related nutrition marker called "lymphocyte × albumin (LA)" and disease-free survival (DFS) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).
METHODS
In total, 711 non-metastatic breast cancer patients who underwent NAC at two medical centers were retrospectively analyzed. We performed least absolute shrinkage and selection operator (LASSO) Cox regression analysis as well as multivariate Cox regression analyses to identify the variables associated with DFS and to establish a predictive nomogram.
RESULTS
The nomogram incorporated four variables based on the multivariate analysis of DFS in the training cohort: LA, ypN stage, ypT stage, and hormone receptor status. In comparison with the traditional TNM staging system, the nomogram demonstrated superior discrimination, calibration ability, and clinical usefulness in both the training set and internal and external validation sets. Furthermore, patients stratified into different risk groups resulted in significant differences in DFS.
CONCLUSIONS
LA is an independent prognostic biomarker, and LA-based prognostic nomogram offers a more precise assessment of DFS for breast cancer patients treated with NAC, potentially serving as a valuable tool for personalized prognostic predictions.
Topics: Humans; Female; Neoadjuvant Therapy; Breast Neoplasms; Cohort Studies; Retrospective Studies; Prognosis; Biomarkers; Albumins
PubMed: 37836576
DOI: 10.3390/nu15194292 -
Molecules (Basel, Switzerland) Dec 2022Albumin nanocolloids have been used as radiopharmaceuticals for more than 40 years. Their main use is in lymphoscintigraphy and the detection of the sentinel lymph node... (Review)
Review
Albumin nanocolloids have been used as radiopharmaceuticals for more than 40 years. Their main use is in lymphoscintigraphy and the detection of the sentinel lymph node as part of the surgical treatment of a variety of solid tumours. The main licensed products are labelled with the gamma emitter technetium-99m. Recently, two analogues labelled with positron emitters have been reported, using gallium-68 and zirconium-89. For about 10 years, there has been interest in dual-modal agents with both radioactive and fluorescent labels to improve the localisation of the sentinel lymph node. Indocyanine green (ICG) has been the most widely used fluorescent label, largely due to its availability as a licensed agent and its ease of application. The further development of alternative radiolabels or improved fluorescent tags will require investment in the development and licensing. There is also a vast potential for the targeting of albumin nanocolloids using existing strategies, which could be promising for the development of both diagnostic and therapeutic agents.
Topics: Radiopharmaceuticals; Technetium Tc 99m Aggregated Albumin; Sentinel Lymph Node Biopsy; Lymphoscintigraphy; Coloring Agents; Albumins; Lymph Nodes
PubMed: 36500689
DOI: 10.3390/molecules27238596 -
Toxins Feb 2022Uremic toxins are a heterogeneous group of molecules that accumulate in the body due to the progression of chronic kidney disease (CKD). These toxins are associated with... (Review)
Review
Uremic toxins are a heterogeneous group of molecules that accumulate in the body due to the progression of chronic kidney disease (CKD). These toxins are associated with kidney dysfunction and the development of comorbidities in patients with CKD, being only partially eliminated by dialysis therapies. Importantly, drugs used in clinical treatments may affect the levels of uremic toxins, their tissue disposition, and even their elimination through the interaction of both with proteins such as albumin and cell membrane transporters. In this context, protein-bound uremic toxins (PBUTs) are highlighted for their high affinity for albumin, the most abundant serum protein with multiple binding sites and an ability to interact with drugs. Membrane transporters mediate the cellular influx and efflux of various uremic toxins, which may also compete with drugs as substrates, and both may alter transporter activity or expression. Therefore, this review explores the interaction mechanisms between uremic toxins and albumin, as well as membrane transporters, considering their potential relationship with drugs used in clinical practice.
Topics: Albumins; Drug Interactions; Female; Humans; Male; Membrane Transport Proteins; Renal Insufficiency, Chronic; Toxins, Biological; Uremia; Uremic Toxins
PubMed: 35324674
DOI: 10.3390/toxins14030177 -
Nutrients Nov 2021Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2-4 years after the first diagnosis of ascites. Albumin is an important tool... (Review)
Review
Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2-4 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.
Topics: Albumins; Ascites; Hepatorenal Syndrome; Humans; Inflammation; Liver Cirrhosis; Liver Diseases; Peritonitis; Serum Albumin; Zinc
PubMed: 34836265
DOI: 10.3390/nu13114011 -
Physiological Reports Mar 2022Circulating albumin is expected to play a significant role in the trafficking of plasma free fatty acids (FFA) between tissues, such as FFA transfer from adipose tissue...
Circulating albumin is expected to play a significant role in the trafficking of plasma free fatty acids (FFA) between tissues, such as FFA transfer from adipose tissue to the liver. However, it was not yet known how disrupting FFA binding to albumin in circulation would alter lipid metabolism and any resulting impacts upon control of glycemia. To improve understanding of metabolic control, we aimed to determine whether lack of serum albumin would decrease plasma FFA, hepatic lipid storage, whole body substrate oxidation, and glucose metabolism. Male and female homozygous albumin knockout mice and C57BL/6J wild type controls, each on a standard diet containing a moderate fat content, were studied at 6-8 weeks of age. Indirect calorimetry, glucose tolerance testing, insulin tolerance testing, exercise performance, plasma proteome, and tissue analyses were performed. In both sexes of albumin knockout mice compared to the wild type mice, significant reductions (p < 0.05) were observed for plasma FFA concentration, hepatic triacylglycerol and diacylglycerol content, blood glucose during the glucose tolerance test, and blood glucose during the insulin tolerance test. Albumin deficiency did not reduce whole body fat oxidation over a 24-h period and did not alter exercise performance in an incremental treadmill test. The system-level phenotypic changes in lipid and glucose metabolism were accompanied by reduced hepatic perilipin-2 expression (p < 0.05), as well as increased expression of adiponectin (p < 0.05) and glucose transporter-4 (p < 0.05) in adipose tissue. The results indicate an important role of albumin and plasma FFA concentration in lipid metabolism and glucoregulation.
Topics: Albumins; Animals; Blood Glucose; Fatty Acids, Nonesterified; Female; Insulin; Insulin Resistance; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout
PubMed: 35238481
DOI: 10.14814/phy2.15161 -
ESC Heart Failure Apr 2024The combination of haemoglobin, albumin, lymphocytes, and platelets (HALP) is a new metric used to assess patient prognosis in many diseases. This study aimed to assess... (Meta-Analysis)
Meta-Analysis
AIMS
The combination of haemoglobin, albumin, lymphocytes, and platelets (HALP) is a new metric used to assess patient prognosis in many diseases. This study aimed to assess the relationship between HALP and short- and long-term mortality in patients with heart failure.
METHODS AND RESULTS
This retrospective cohort study included adult patients with heart failure who were hospitalized between 2019 and 2021. The primary outcomes were 1-month mortality and 1-year mortality. The multivariable logistic regression analysis was used to evaluate the association between HALP and the risk of mortality. Stratified analyses were conducted based on New York Heart Association functional classification (NYHA) stage (II/III, IV) and left ventricular ejection fraction (LVEF, <50%, ≥50%). The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability of HALP, prognostic nutritional index (PNI), C-reactive protein (CRP), and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score in predicting mortality in patients with heart failure. A total of 730 patients with heart failure were included, of whom 61 (8.36%) died within 1 month and 77 (10.55%) died within 1 year. High HALP scores were associated with a reduced risk of 1-month mortality (odds ratio (OR) = 0.978, 95% confidence interval (CI): 0.963-0.992, P = 0.003) and 1-year mortality (OR = 0.987, 95% CI: 0.977-0.997, P = 0.009) in patients with heart failure. In patients with different NYHA stages or LVEF levels, high HALP scores were correlated with a reduced risk of 1-year mortality in patients with NYHA stage II/III (OR = 0.978, 95% CI: 0.957-1.000, P = 0.045) or LVEF ≥50% (OR = 0.970, 95% CI: 0.945-0.996, P = 0.024). The AUC for HALP, PNI, CRP, and MAGGIC-HF to predict 1-year mortality in patients with heart failure were 0.677 (95% CI: 0.619-0.735), 0.666 (95% CI: 0.608-0.723), 0.638 (95% CI: 0.572-0.704), and 0.654 (95% CI: 0.591-0.717), respectively.
CONCLUSIONS
HALP may be a potential marker for predicting mortality in patients with heart failure. Further exploration based on HALP may yield better clinical predictors of prognosis in patients with heart failure.
Topics: Adult; Humans; Stroke Volume; Retrospective Studies; Ventricular Function, Left; Heart Failure; Albumins; Lymphocytes; Hemoglobins
PubMed: 38243382
DOI: 10.1002/ehf2.14662