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1.
Nutrients ; 16(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38931154

RESUMO

Psoriasis is a chronic systemic disease with a multifaceted pathomechanism and immunological basis, with the presence of inflammatory skin lesions and joint ailments. Diseases accompanying psoriasis include metabolic and cardiovascular disorders. It has been suggested that inflammation is involved in the development of each of these conditions. The main objective of this study was to analyse the fatty acid profile, including polyunsaturated fatty acids, in the erythrocyte membranes of patients suffering from psoriasis. A total of 58 adult patients of the Department of Skin and Venereal Diseases of the Pomeranian Medical University in Szczecin, suffering from psoriasis, were qualified for this study. The patients had undergone an interview and physical examination, during which the severity of psoriasis was assessed. All patients had their weight and height measured to assess their body mass index (BMI). After 3 months of treatment, biochemical parameters (ALT, AST, total cholesterol) and inflammatory markers (CRP) in the blood were assessed. In addition, the isolation of fatty acids (PUFAs, SFAs, MUFAs) from erythrocyte membranes and the qualitative and quantitative analysis of their profile using a gas chromatograph were carried out. In patients with severe psoriasis requiring systemic treatment, an altered profile of fatty acids in erythrocyte membranes was found, including a significantly lower concentration of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a significantly higher concentration of saturated fatty acids; and a decreased concentration of oleic acid (omega-9), compared to the results obtained in patients with less severe psoriasis receiving topical treatment. In patients with psoriasis and BMI ≥ 25, significantly higher concentrations of AST and ALT in the blood and significantly higher concentrations of pro-inflammatory arachidonic acid in erythrocyte membranes were found. Elevated concentrations of saturated (R = 0.31) and monounsaturated fatty acids (R = 0.29) may correlate with a greater severity of psoriasis.


Assuntos
Membrana Eritrocítica , Ácidos Graxos , Psoríase , Humanos , Psoríase/sangue , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/química , Feminino , Masculino , Pessoa de Meia-Idade , Ácidos Graxos/sangue , Adulto , Índice de Massa Corporal , Ácidos Graxos Insaturados/sangue , Índice de Gravidade de Doença , Biomarcadores/sangue , Idoso
2.
Nanoscale ; 16(25): 11863-11878, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38841898

RESUMO

Red blood cells (RBCs), which function as material transporters in organisms, are rich in materials that are exchanged with metabolically active tumor cells. Recent studies have demonstrated that tumor cells can regulate biological changes in RBCs, including influencing differentiation, maturation, and morphology. RBCs play an important role in tumor development and immune regulation. Notably, the novel scientific finding that RBCs absorb fragments of tumor-carrying DNA overturns the conventional wisdom that RBCs do not contain nucleic acids. RBC membranes are excellent biomimetic materials with significant advantages in terms of their biocompatibility, non-immunogenicity, non-specific adsorption resistance, and biodegradability. Therefore, RBCs provide a new research perspective for the development of tumor liquid biopsies, molecular imaging, drug delivery, and other tumor precision diagnosis and treatment technologies.


Assuntos
Eritrócitos , Neoplasias , Humanos , Eritrócitos/metabolismo , Neoplasias/terapia , Neoplasias/diagnóstico , Neoplasias/patologia , Medicina de Precisão , Animais , Sistemas de Liberação de Medicamentos , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Materiais Biomiméticos/química
3.
Molecules ; 29(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38893395

RESUMO

High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the induction and progression of many diseases. The high reactivity of acrolein towards the thiol and amino groups of amino acids may cause damage to cell proteins. Acrolein may be responsible for the induction of oxidative stress in cells. We hypothesized that acrolein may contribute to the protein damage in erythrocytes, leading to the disruption of the structure of cell membranes. The lipid membrane fluidity, membrane cytoskeleton, and osmotic fragility were measured for erythrocytes incubated with acrolein for 24 h. The levels of thiol, amino, and carbonyl groups were determined in cell membrane and cytosol proteins. The level of non-enzymatic antioxidant potential (NEAC) and TBARS was also measured. The obtained research results showed that the exposure of erythrocytes to acrolein causes changes in the cell membrane and cytosol proteins. Acrolein stiffens the cell membrane of erythrocytes and increases their osmotic sensitivity. Moreover, it has been shown that erythrocytes treated with acrolein significantly reduce the non-enzymatic antioxidant potential of the cytosol compared to the control.


Assuntos
Acroleína , Citosol , Membrana Eritrocítica , Eritrócitos , Acroleína/farmacologia , Acroleína/toxicidade , Acroleína/metabolismo , Citosol/metabolismo , Citosol/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteínas de Membrana/metabolismo , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Fluidez de Membrana/efeitos dos fármacos , Fragilidade Osmótica/efeitos dos fármacos
4.
Int J Mol Sci ; 25(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38892001

RESUMO

The deformability of red blood cells (RBCs), expressing their ability to change their shape as a function of flow-induced shear stress, allows them to optimize oxygen delivery to the tissues and minimize their resistance to flow, especially in microcirculation. During physiological aging and blood storage, or under external stimulations, RBCs undergo metabolic and structural alterations, one of which is hemoglobin (Hb) redistribution between the cytosol and the membrane. Consequently, part of the Hb may attach to the cell membrane, and although this process is reversible, the increase in membrane-bound Hb (MBHb) can affect the cell's mechanical properties and deformability in particular. In the present study, we examined the correlation between the MBHb levels, determined by mass spectroscopy, and the cell deformability, determined by image analysis. Six hemoglobin subunits were found attached to the RBC membranes. The cell deformability was negatively correlated with the level of four subunits, with a highly significant inter-correlation between them. These data suggest that the decrease in RBC deformability results from Hb redistribution between the cytosol and the cell membrane and the respective Hb interaction with the cell membrane.


Assuntos
Deformação Eritrocítica , Membrana Eritrocítica , Hemoglobinas , Humanos , Membrana Eritrocítica/metabolismo , Hemoglobinas/metabolismo , Eritrócitos/metabolismo , Ligação Proteica
5.
Neuroimage ; 296: 120666, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38830440

RESUMO

Direct imaging of semi-solid lipids, such as myelin, is of great interest as a noninvasive biomarker of neurodegenerative diseases. Yet, the short T2 relaxation times of semi-solid lipid protons hamper direct detection through conventional magnetic resonance imaging (MRI) pulse sequences. In this study, we examined whether a three-dimensional ultrashort echo time (3D UTE) sequence can directly acquire signals from membrane lipids. Membrane lipids from red blood cells (RBC) were collected from commercially available blood as a general model of the myelin lipid bilayer and subjected to D2O exchange and freeze-drying for complete water removal. Sufficiently high MR signals were detected with the 3D UTE sequence, which showed an ultrashort T2* of ∼77-271 µs and a short T1 of ∼189 ms for semi-solid RBC membrane lipids. These measurements can guide designing UTE-based sequences for direct in vivo imaging of membrane lipids.


Assuntos
Membrana Eritrocítica , Imageamento por Ressonância Magnética , Lipídeos de Membrana , Bainha de Mielina , Humanos , Imageamento por Ressonância Magnética/métodos , Bainha de Mielina/química , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Lipídeos de Membrana/química , Liofilização , Eritrócitos/metabolismo
6.
Dokl Biol Sci ; 516(1): 50-54, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700814

RESUMO

The content of membrane-bound methemoglobin (MtHb) in nucleated erythrocytes was studied in the black scorpionfish Scorpaena porcus (Linnaeus, 1758) in vitro. Spectral characteristics were determined for a whole hemolysate, a hemolysate obtained by stroma precipitation (a clarified hemolysate), and a resuspended stroma. The MtHb proportion in the erythrocyte stroma was found to exceed 80% (6.20 ± 0.59 µM). Clarified hemolysates were nearly free of MtHb (0.5 ± 0.2 µM). Membrane-bound ferric hemoglobin did not affect the erythrocyte resistance to osmotic shock. The osmotic fragility range was determined using a LaSca-TM laser microparticle analyzer (BioMedSystems, Russia) to be 102-136 mOsm/kg, much the same as in other bony fish species. A nitrite load (10 mg/L) significantly increased the MtHb content in the blood. However, the membrane-bound ferric hemoglobin content did not change significantly, amounting to 6.34 ± 1.09 µM (approximately 95%). The finding suggested a functional importance for MtHb present in the plasma membrane of nucleated erythrocytes. Membrane-bound MtHb was assumed to neutralize the external oxidative load and the toxic effect of hydrogen sulfide in bottom water layers, where the species lives.


Assuntos
Metemoglobina , Perciformes , Animais , Metemoglobina/metabolismo , Perciformes/metabolismo , Perciformes/sangue , Hemoglobinas/metabolismo , Fragilidade Osmótica , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/efeitos dos fármacos , Eritroblastos/metabolismo , Peixes/metabolismo , Peixes/sangue
7.
Psychiatry Res ; 337: 115966, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810536

RESUMO

Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.


Assuntos
Membrana Eritrocítica , Bainha de Mielina , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Masculino , Feminino , Membrana Eritrocítica/metabolismo , Adulto Jovem , Adolescente , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Anisotropia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/metabolismo , Ácidos Graxos/metabolismo , Adulto , Imagem de Tensor de Difusão , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Ácidos Docosa-Hexaenoicos/metabolismo , Escalas de Graduação Psiquiátrica , Ácidos Graxos Insaturados/metabolismo
8.
Nutrients ; 16(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794744

RESUMO

Mounting evidence indicates a complex link between circulating saturated fatty acids (SFAs) and cardiovascular disease (CVD) risk factors, but research on erythrocyte membrane SFA associations with metabolic markers remains limited. Our study sought to investigate the correlations between erythrocyte membrane SFAs and key metabolic markers within glycemic and lipid metabolism in a Chinese population of 798 residents aged 41 to 71 from Guangzhou. Using gas chromatography-mass spectrometry, we assessed the erythrocyte membrane saturated fatty acid profile and performed multiple linear regression to evaluate the relationship between different SFA subtypes and metabolic markers. Our findings revealed that the odd-chain SFA group (C15:0 + C17:0) exhibited negative associations with fasting blood glucose (FBG), homeostatic model assessment for insulin resistance (HOMA-IR), and triglycerides (TG). Conversely, the very-long-chain SFA group (C20:0 + C22:0 + C23:0 + C24:0) exhibited positive associations with fasting insulins (FINS), HOMA-IR, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Furthermore, there was no evidence supporting an association between the even-chain group (C14:0 + C16:0 + C18:0) and metabolic markers. Our findings suggest that different subtypes of SFAs have diverse effects on glycemic and lipid metabolic markers, with odd-chain SFAs associated with a lower metabolic risk. However, the results concerning the correlations between even-chain SFAs and very-long-chain SFAs with markers of glycemic and lipid metabolism pathways are confusing, highlighting the necessity for further exploration and investigation.


Assuntos
Biomarcadores , Glicemia , Membrana Eritrocítica , Ácidos Graxos , Humanos , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Ácidos Graxos/sangue , Feminino , Idoso , Glicemia/metabolismo , Biomarcadores/sangue , Membrana Eritrocítica/metabolismo , Adulto , China , Resistência à Insulina , Metabolismo dos Lipídeos/fisiologia , Povo Asiático , Triglicerídeos/sangue , Insulina/sangue , População do Leste Asiático
9.
Int J Mol Sci ; 25(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38791153

RESUMO

Garlic is known to have diverse effects on mammalian cells, being cytotoxic, especially to cancer cells, but also protect against oxidative stress. Mammalian erythrocyte is a simple cell devoid of intracellular organelles, protein synthesis ability, and most signaling pathways. Therefore, examination of the effects of garlic on erythrocytes allows for revealing primary events in the cellular action of garlic extract. In this study, human erythrocytes or erythrocyte membranes were exposed to garlic extract at various dilutions. Hemoglobin oxidation to methemoglobin, increased binding of hemoglobin to the membrane, and formation of Heinz bodies were observed. Garlic extract depleted acid-soluble thiols, especially glutathione, and induced a prooxidative shift in the cellular glutathione redox potential. The extract increased the osmotic fragility of erythrocytes, induced hemolysis, and inhibited hemolysis in isotonic ammonium chloride, indicative of decreased membrane permeability for Cl- and increased the membrane fluidity. Fluorescent probes indicated an increased level of reactive oxygen species and induction of lipid peroxidation, but these results should be interpreted with care since the extract alone induced oxidation of the probes (dichlorodihydrofluorescein diacetate and BODIPY C11). These results demonstrate that garlic extract induces oxidative changes in the erythrocyte, first of all, thiol and hemoglobin oxidation.


Assuntos
Eritrócitos , Alho , Hemólise , Oxirredução , Extratos Vegetais , Alho/química , Humanos , Extratos Vegetais/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemólise/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Hemoglobinas/metabolismo , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo , Fragilidade Osmótica/efeitos dos fármacos
10.
J Trauma Acute Care Surg ; 97(1): 57-64, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38605437

RESUMO

BACKGROUND: Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor. METHODS: Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow. RESULTS: Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model. CONCLUSION: Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.


Assuntos
Cálcio , Eritrócitos , Fosfatidilserinas , Tromboplastina , Trombose , Humanos , Fosfatidilserinas/metabolismo , Tromboplastina/metabolismo , Cálcio/metabolismo , Trombose/metabolismo , Trombose/etiologia , Eritrócitos/metabolismo , Agregação Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Plasma Rico em Plaquetas/metabolismo
11.
Cryobiology ; 115: 104898, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663665

RESUMO

Trehalose is widely acknowledged for its ability to stabilize plasma membranes during dehydration. However, the exact mechanism by which trehalose interacts with lipid bilayers remains presently unclear. In this study, we conducted atomistic molecular dynamic simulations on asymmetric model bilayers that mimic the membrane of human red blood cells at various trehalose and water contents. We considered three different hydration levels mimicking the full hydration to desiccation scenarios. Results indicate that the asymmetric distribution of lipids did not significantly influence the computed structural characteristics at full and low hydration. At dehydration, however, the order parameter obtained from the symmetric bilayer is significantly higher compared to those obtained from asymmetric ones. Analysis of hydrogen bonds revealed that the protective ability of trehalose is well described by the water replacement hypothesis at full and low hydration, while at dehydration other interaction mechanisms associated with trehalose exclusion from the bilayer may involve. In addition, we found that trehalose exclusion is not attributed to sugar saturation but rather to the reduction in hydration levels. It can be concluded that the protective effect of trehalose is not only related to the hydration level of the bilayer, but also closely tied to the asymmetric distribution of lipids within each leaflet.


Assuntos
Membrana Eritrocítica , Ligação de Hidrogênio , Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Trealose , Trealose/metabolismo , Trealose/química , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Humanos , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/química , Água/química , Água/metabolismo , Eritrócitos/metabolismo , Eritrócitos/química , Dessecação
12.
Urologiia ; (1): 24-30, 2024 Mar.
Artigo em Russo | MEDLINE | ID: mdl-38650402

RESUMO

AIM: To determine the effect of standard treatment on changes in the structural and functional properties of erythrocytes in obstructive and non-obstructive acute pyelonephritis. MATERIALS AND METHODS: The structural and functional properties of erythrocytes and their intracellular metabolism in 78 patients with a diagnosis of primary non-obstructive and secondary obstructive acute pyelonephritis, randomized by age, gender, and the minimum number of concomitant diseases were investigated. RESULTS AND DISCUSSION: In acute non-obstructive pyelonephritis, changes of the content of proteins in circulating erythrocytes responsible for the structure formation and stabilization of the plasma membrane (-spectrin, anion transport protein, pallidin, protein 4.1), intracellular metabolism (anion transport protein, glutathione-S-transferase), membrane flexibility and shape (actin, tropomyosin) are insignificant, alike from acute obstructive pyelonephritis. In addition, processes of lipid peroxidation inside red blood cells are intensified, and oxidative stress develops with a decrease in the sorption capacity of erythrocytes, as well as the content and ratio of lipid fractions in the plasma membrane, which form the basis of the lipid components and play the main role in the sequencing of protein macromolecules and the normal metabolism of red blood cells. CONCLUSION: In acute obstructive pyelonephritis, changes in the content and ratio of proteins and lipids in the erythrocyte membrane lead to functional rearrangements that are not corrected by standard treatment.


Assuntos
Eritrócitos , Pielonefrite , Humanos , Pielonefrite/sangue , Pielonefrite/metabolismo , Eritrócitos/metabolismo , Feminino , Masculino , Doença Aguda , Adulto , Pessoa de Meia-Idade , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/química
13.
Br J Haematol ; 204(5): 2025-2039, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38613149

RESUMO

Splenectomised ß-thalassaemia/haemoglobin E (HbE) patients have increased levels of circulating microparticles or medium extra-cellular vesicles (mEVs). The splenectomised mEVs play important roles in thromboembolic complications in patients since they can induce platelet activation and endothelial cell dysfunction. However, a comprehensive understanding of the mechanism of mEV generation in thalassaemia disease has still not been reached. Thalassaemic mEVs are hypothesised to be generated from cellular oxidative stress in red blood cells (RBCs) and platelets. Therefore, a proteomic analysis of mEVs from splenectomised and non-splenectomised ß-thalassaemia/HbE patients was performed by liquid chromatography with tandem mass spectrometry. A total of 171 proteins were identified among mEVs. Interestingly, 72 proteins were uniquely found in splenectomised mEVs including immunoglobulin subunits and cytoskeleton proteins. Immunoglobulin G (IgG)-bearing mEVs in splenectomised patients were significantly increased. Furthermore, complement C1q was detected in both mEVs with IgG binding and mEVs without IgG binding. Interestingly, the percentage of mEVs generated from RBCs with IgG binding was approximately 15-20 times higher than the percentage of RBCs binding with IgG. This suggested that the vesiculation of thalassaemia mEVs could be a mechanism of RBCs to eliminate membrane patches harbouring immune complex and may consequently prevent cells from phagocytosis and lysis.


Assuntos
Hemoglobina E , Proteômica , Talassemia beta , Humanos , Talassemia beta/sangue , Talassemia beta/metabolismo , Hemoglobina E/metabolismo , Proteômica/métodos , Feminino , Masculino , Adulto , Vesículas Extracelulares/metabolismo , Esplenectomia , Imunoglobulina G/sangue , Membrana Eritrocítica/metabolismo , Proteoma/análise , Adolescente , Eritrócitos/metabolismo , Micropartículas Derivadas de Células/metabolismo , Adulto Jovem
14.
J Control Release ; 369: 325-334, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565395

RESUMO

Challenges for glioma treatment with nanomedicines include physio-anatomical barriers (the blood-brain barrier and blood-brain tumor barrier), low drug loading capacity, and limited circulation time. Here, a red blood cell membrane-coated docetaxel drug nanocrystal (pV-RBCm-NC(DTX)), modified with pHA-VAP (pV) for all-stage targeting of glioma, was designed. The NC(DTX) core exhibited a high drug loading capacity but low in vivo stability, and the RBCm coating significantly enhanced the stability and prolonged in vivo circulation. Moreover, the Y-shaped targeting ligand pV was modified by a mild avidin-biotin interaction, which endowed RBCm-NC(DTX) with superior barrier-crossing ability and therapeutic efficacy. The integration of nanocrystal technology, cell membrane coating, and the avidin-biotin insertion method into this active targeting biomimetic formulation represents a promising drug delivery strategy for glioma.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Docetaxel , Membrana Eritrocítica , Glioma , Nanopartículas , Docetaxel/administração & dosagem , Docetaxel/farmacocinética , Docetaxel/química , Glioma/tratamento farmacológico , Animais , Nanopartículas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/química , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Masculino , Sistemas de Liberação de Medicamentos , Avidina/administração & dosagem , Avidina/química , Humanos , Biotina/química , Biotina/administração & dosagem , Ratos Sprague-Dawley , Barreira Hematoencefálica/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus
15.
Eur Biophys J ; 53(4): 239-247, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38625405

RESUMO

In this study, fluorescence recovery after photobleaching (FRAP) experiments were performed on RBC labeled by lipophilic fluorescent dye CM-DiI to evaluate the role of adenylyl cyclase cascade activation in changes of lateral diffusion of erythrocytes membrane lipids. Stimulation of adrenergic receptors with epinephrine (adrenaline) or metaproterenol led to the significant acceleration of the FRAP recovery, thus indicating an elevated membrane fluidity. The effect of the stimulation of protein kinase A with membrane-permeable analog of cAMP followed the same trend but was less significant. The observed effects are assumed to be driven by increased mobility of phospholipids resulting from the weakened interaction between the intermembrane proteins and RBC cytoskeleton due to activation of adenylyl cyclase signaling cascade.


Assuntos
Adenilil Ciclases , Membrana Eritrocítica , Recuperação de Fluorescência Após Fotodegradação , Fluidez de Membrana , Adenilil Ciclases/metabolismo , Fluidez de Membrana/efeitos dos fármacos , Humanos , Membrana Eritrocítica/metabolismo , Ativação Enzimática , Transdução de Sinais/efeitos dos fármacos , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Epinefrina/farmacologia , Epinefrina/metabolismo
16.
J Colloid Interface Sci ; 663: 856-868, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38447400

RESUMO

Mitochondrial dysfunction and metal ion imbalance are recognized as pathological hallmarks of Alzheimer's Disease (AD), leading to deposition of ß-amyloid (Aß) thereby and inducing neurotoxicity, activating apoptosis, eliciting oxidative stress, and ultimately leading to cognitive impairment. In this study, the red blood cell membrane (RBC) was used as a vehicle for encapsulating carbon quantum dots (CQD) and polydopamine (PDA), creating a nanocomposite (PDA-CQD/RBC). This nanocomposite was combined with near-infrared light (NIR) for AD treatment. The RBC offers anti-immunorecognition properties to evade immune clearance, PDA exhibits enzyme-mimicking activity to mitigate oxidative stress damage, and CQD acts as a chelating agent for metal ions (Cu2+), effectively preventing Cu2+-mediated aggregation of Aß. Furthermore, the local heating induced by near-infrared laser irradiation can dismantle the formed Aß fibers and enhance the blood-brain barrier's permeability. Both in vitro and animal experiments have shown that PDA-CQD/RBC, in combination with NIR, mitigates neuroinflammation, and ameliorates behavioral deficits in mice. This approach targets multiple pathological pathways, surpassing the limitations of single-target treatments and enhancing therapeutic efficacy while decelerating disease progression.


Assuntos
Doença de Alzheimer , Indóis , Polímeros , Pontos Quânticos , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/patologia , Peptídeos beta-Amiloides , Metais , Raios Infravermelhos , Carbono/farmacologia
17.
Maturitas ; 184: 107948, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38447232

RESUMO

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.


Assuntos
Suplementos Nutricionais , Membrana Eritrocítica , Ácidos Graxos Ômega-3 , Óleos de Peixe , Hemoglobinas , Homeostase , Ferro , Obesidade , Redução de Peso , Humanos , Feminino , Pessoa de Meia-Idade , Ácidos Graxos Ômega-3/administração & dosagem , Obesidade/dietoterapia , Obesidade/complicações , Obesidade/sangue , Obesidade/metabolismo , Óleos de Peixe/administração & dosagem , Ferro/sangue , Ferro/metabolismo , Membrana Eritrocítica/metabolismo , Hemoglobinas/metabolismo , Hemoglobinas/análise , Dieta Redutora , Adulto , Restrição Calórica , Fosfolipídeos/sangue
18.
Int J Artif Organs ; 47(3): 155-161, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38425132

RESUMO

Several similarities have been found between shear stress-induced erythrocyte damage and physiological aging of erythrocytes in terms of elevated mechanical fragility, increased erythrocyte aggregation, and decreased membrane surface charge. Accordingly, we hypothesized that blood pump circulation, which generates shear stress, would accelerate erythrocyte aging, manifesting as oxidation. Therefore, the purpose of this study was to investigate the effect of blood pump circulation on erythrocyte oxidation. Fresh porcine blood was acquired from a slaughterhouse and anticoagulated with sodium citrate. About 500 mL of anticoagulated whole blood was circulated for 180 min in an in vitro test circuit comprising a BP-80 blood pump with a pump speed and a pump pressure head of 100-120 mmHg. A blood sample was taken at the start of the circulation and 180 min afterward. The hemolysis level and oxidation amount of the erythrocyte membrane were analyzed and compared between samples. Hemolysis increased with the prolongation of shear exposure inside the pump circuit. After 180 min of blood pumping in circuit, the oxidation level of the erythrocyte membrane showed an increase of 0.1 nmol/mg protein. Moreover, the membrane oxidation levels of sheared erythrocytes were greater than those of control erythrocytes. These results suggest that blood pump circulation accelerates erythrocyte aging and give us a greater understanding of the effects of blood pump perfusion.


Assuntos
Membrana Eritrocítica , Hemólise , Suínos , Animais , Hemólise/fisiologia , Eritrócitos , Estresse Mecânico
19.
Int J Pharm ; 655: 124007, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38493844

RESUMO

Gold core mesoporous silica shell (AuMSS) nanorods are multifunctional nanomedicines that can act simultaneously as photothermal, drug delivery, and bioimaging agents. Nevertheless, it is reported that once administrated, nanoparticles can be coated with blood proteins, forming a protein corona, that directly impacts on nanomedicines' circulation time, biodistribution, and therapeutic performance. Therefore, it become crucial to develop novel alternatives to improve nanoparticles' half-life in the bloodstream. In this work, Polyethylenimine (PEI) and Red blood cells (RBC)-derived membranes were combined for the first time to functionalize AuMSS nanorods and simultaneously load acridine orange (AO). The obtained results revealed that the RBC-derived membranes promoted the neutralization of the AuMSS' surface charge and consequently improved the colloidal stability and biocompatibility of the nanocarriers. Indeed, the in vitro data revealed that PEI/RBC-derived membranes' functionalization also improved the nanoparticles' cellular internalization and was capable of mitigating the hemolytic effects of AuMSS and AuMSS/PEI nanorods. In turn, the combinatorial chemo-photothermal therapy mediated by AuMSS/PEI/RBC_AO nanorods was able to completely eliminate HeLa cells, contrasting with the less efficient standalone therapies. Such data reinforce the potential of AuMSS nanomaterials to act simultaneously as photothermal and chemotherapeutic agents.


Assuntos
Antineoplásicos , Nanotubos , Neoplasias , Humanos , Células HeLa , Terapia Fototérmica , Membrana Eritrocítica , Dióxido de Silício , Ouro , Distribuição Tecidual , Fototerapia , Doxorrubicina/farmacologia , Neoplasias/tratamento farmacológico
20.
J Drug Target ; 32(5): 544-556, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38469874

RESUMO

Radio-photothermal therapy is an effective modality for cancer treatment. To overcome the radio-resistance in the hypoxic microenvironment and improve the sensitivity of radiotherapy, metal nanoparticles, and radio-photothermal therapy are widely used in the research of improving the curative effect and reducing the side effects of radiotherapy. Here, we developed red blood membrane camouflaging bismuth nanoflowers (RBCM-BNF) with outstanding physiological stability and biodegradability for lung tumours. In vitro data proved that the RBCM-BNF had the greatest cancer cell-killing ability combined with X-ray irradiation and photo-thermal treatment. Meanwhile, in vivo studies revealed that RBCM-BNF can alleviate the hypoxic microenvironment and promote tumour cell apoptosis by inhibiting HIF-1α expression and increasing caspase-3 expression. Therefore, RBCM-BNF had a good radio-sensitising effect and might be a promising biomimetic nanoplatform as a therapeutic target for cancer.


Assuntos
Bismuto , Membrana Eritrocítica , Neoplasias Pulmonares , Terapia Fototérmica , Bismuto/química , Neoplasias Pulmonares/terapia , Animais , Humanos , Terapia Fototérmica/métodos , Camundongos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Nanopartículas/química , Camundongos Nus , Microambiente Tumoral , Células A549 , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
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