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Albumin preserves and enhances lung cell GSH levels. (A) A549 cells were pretreated with either 0% (open circles) or 2% (closed circles) HSA for 4-24 h in RPMI and treated with 1% Triton X-100 to measure cell GSH using the enzymatic DTNB recycling assay. (B) Either A549 (closed circles), HFL1 cells (closed triangles), or peripheral blood lymphocytes (PBL) (open diamonds) were incubated with 0-2% human serum albumin for 18 h (A549 and HFL1 cells) or 48 h (lymphocytes) at 37 C, followed by treatment with 1% Triton X-100 to determine cell GSH. (A: n 4 and results are representative of four separate experiments. B: n 4 for A549 and PBL; n 5 for HFL1 cells.)
Source publication
Human serum albumin (HSA) is a cystine-rich serum protein taken up by many cells through receptor-mediated and fluid-phase endocytosis. We hypothesized that HSA may play a role in modulating cellular antioxidant redox signaling. Lung epithelial cells (A549), fibroblasts (HFL1), and blood lymphocytes had increased glutathione (GSH) levels after 8 h...
Contexts in source publication
Context 1
... cells incubated with 2% HSA had significantly higher cellular GSH levels as early as 8 h (11.19 0.17 versus 7.15 0.14, p 0.001), and the difference between cells incubated with and without HSA was accentuated throughout the 24-h incubation period (Figure 2A). Between 4 and 12 h cells incu- bated without HSA showed a progressive decrease in GSH. ...
Context 2
... 4 and 12 h cells incu- bated without HSA showed a progressive decrease in GSH. In addition to the A549 cells (closed circles), HFL1 cells (closed triangles), and peripheral blood lymphocytes (open diamonds) showed a dose-dependent increase in GSH levels upon incu- bation with HSA ( Figure 2B). All cell lines had significantly higher GSH levels when cultured in 0.5% HSA (p 0.05 for all compared with HSA). ...
Citations
... This discrepancy may result from low albumin indicating reduced protein stor-age, subsequently stimulating catabolic processes leading to muscle breakdown. In addition, albumin serves as a specific regulator of cellular glutathione, a critical antioxidant [22]. Thus, glutathione plays a crucial role in mitigating oxidative stress, which is particularly important to the agerelated decline of skeletal muscle [23]. ...
... Direct anti-apoptotic activity of albumin has been observed in human endothelial cells [35]. It has been demonstrated that free thiols of albumin play a significant role in determining the DNA-binding activity of active transcription factors such as NF-κB, thereby potentially influencing processes that determine cellular fate apoptosis [36]. ...
Intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality. Secondary brain injury after surviving the initial ictus leads to severe neurological deficits, and has emerged as an attractive therapeutic target. Human serum albumin (HSA), a pluripotent protein synthesized mainly in the liver, has shown remarkable efficacy by targeting secondary brain injury pathways in rodent models of ICH, while results from relevant clinical research on albumin therapy remain unclear. Preclinical studies have shown albumin-mediated neuroprotection may stem from its biological functions, including its major antioxidation activity, anti-inflammatory responses, and anti-apoptosis. HSA treatment provides neuroprotective and recovery enhancement effects via improving short and long-term neurologic function, maintaining blood-brain barrier (BBB) integrity and reducing neuronal oxidative stress and apoptosis. Retrospective clinical studies have shown that admission hypoalbuminemia is a prognostic factor for poor outcomes in patients with ICH. However, clinical trial was terminated due to poor enrollment and its potential adverse effects. This review provides an overview of the physiological properties of albumin, as well as its potential neuroprotective and prognostic value and the resulting clinical implications.
... A common theme in Long COVID and ME/CFS may be an aberrant response to an immunological trigger, like infection, resulting in a sustained dysregulated immune system because of overactivation of CD8 T-cells and subsequent dysfunction, reminiscent of CD8 T-cell clonal exhaustion. Compounds in the nebulized antioxidant/anti-pathogen agent can act to attenuate Nuclear Factor Kappa B (NF-κB) signaling (Kim et al., 2015;Greiner et al., 2013;Francomano FC et al., 2019;Oka et al., 2000;Sudhoff et al., 2015;Yadav and Chandra, 2017;Cantin et al., 2000;Lou and Kaplowitz, 2007;Xu et al., 2016), potentially decreasing CD8 T-cell abnormalities, including T-cell dysfunction. Clonal T-cell exhaustion can lead to further oxidative stress, and compounds in this nebulized treatment have been shown to decrease oxidative stress by scavenging oxygen and other free radical species (Maes et al., 2011(Maes et al., , 2012a(Maes et al., , 2012b(Maes et al., , 2021Dennis et al., 2021;Kumar et al., 2020;Wu, 2020;Al-Hakeim et al., 2023;Fukuda et al., 1994;Paul et al., 2021;Takemoto et al., 2021;Gould et al., 2010Gould et al., , 2011Gould et al., , 2015Prousky, 2007;Rusznak et al., 2000;Buhl et al., 1990;Dekhuijzen, 2004;Straface et al., 2000;Bridgeman et al., 1991;Hagiwara et al., 2000;Paulin et al., 2017;Lima et al., 2013;Juergens et al., 2003Juergens et al., , 2004Juergens et al., , 2018Juergens et al., , 2020Rhoden et al., 2004;Kennedy-Feitosa et al., 2016;Dahham et al., 2015;Machado et al., 2018;Kim et al., 2015). ...
... As many different persistent pathogens have been associated with ME/CFS as potentially causative or contributing to disease via reactivation, viruses such as EBV, CMV, HHV-6, HHV-7, HHV-8, (Unger et al., 2017;Buchwald et al., 1992;Ablashi et al., 2000), human parvovirus B19 (B19V), enteroviruses (O'Neal and Hanson, 2021;Chia andChia, 2008), lentivirus, andbacteria (Beyond Myalgic Encephalomyelitis, 2015) such as mycoplasma, lyme and Q-fever, this nebulized agent could potentially help dampen pathogen load of multiple infectious agents at the same time. This nebulized treatment also has multiple ingredients capable of acting as immune modulators through their ability to attenuate NF-κB signaling, a process essential for signaling through the TCR, thus decreasing over-activation and potentially averting subsequent dysfunctional CD8 T-cells (Kim et al., 2015;Greiner et al., 2013;Francomano FC et al., 2019;Oka et al., 2000;Sudhoff et al., 2015;Yadav and Chandra, 2017;Cantin et al., 2000;Lou and Kaplowitz, 2007;Xu et al., 2016;Wenzel et al., 2021;Attiq et al., 2021;Davies et al., 2021). ...
Background
Patients with post-acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC, i.e., Long COVID) have a symptom complex highly analogous to many features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting they may share some aspects of pathogenesis in these similar disorders. ME/CFS is a complex disease affecting numerous organ systems and biological processes and is often preceded by an infection-like episode. It is postulated that the chronic manifestations of illness may result from an altered host response to infection or inability to resolve inflammation, as is being reported in Long COVID. The immunopathogenesis of both disorders is still poorly understood. Here, we show data that suggest Long COVID and ME/CFS may be due to an aberrant response to an immunological trigger-like infection, resulting in a dysregulated immune system with CD8 T-cell dysfunction reminiscent of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress. As there is an urgent need for diagnostic tools and treatment strategies for these two related disabling disorders, here, in a retrospective case series, we have also identified a potential nebulized antioxidant/anti-pathogen treatment that has evidence of a good safety profile. This nebulized agent is comprised of five ingredients previously reported individually to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. Administration of this treatment by nebulizer results in rapid access of small doses of well-studied antioxidants and agents with anti-pathogen potential to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system.
Methods
and Findings: We conducted an analysis of CD8 T-cell function and severity of symptoms by self-report questionnaires in ME/CFS, Long COVID and healthy controls. We developed a CD8 T-cell functional assay, assessing CD8 T-cell dysfunction by intracellular cytokine staining (ICS) in a group of ME/CFS (n = 12) and Long COVID patients (n = 8), comparing to healthy controls (HC) with similar age and sex (n = 10). Magnet-enriched fresh CD8 T-cells in both patient groups had a significantly diminished capacity to produce both cytokines, IFNγ or TNFα, after PMA stimulation when compared to HC. The symptom severity questionnaire showed similar symptom profiles for the two disorders. Fortuitously, through a retrospective case series, we were able to examine the ICS and questionnaire data of 4 ME/CFS and 4 Long COVID patients in conjunction with their treatment (3–15 months). In parallel with the treatment pursued electively by participants in this retrospective case series, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%. No serious treatment-associated side effects or laboratory anomalies were noted in these patients.
Conclusions
Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an immunomodulatory, antioxidant pharmacological treatment with anticipated anti-pathogen activity. This work provides evidence of the potential utility of a biomarker, CD8 T-cell dysfunction, and suggests the potential for benefit from a new nebulized antioxidant/anti-pathogen treatment. These immune biomarker data may help build capacity for improved diagnosis and tracking of treatment outcomes during clinical trials for both Long COVID and ME/CFS while providing clues to new treatment avenues that suggest potential efficacy for both conditions.
... Albumin, the most abundant plasma protein, is exclusively synthesized by the liver, and its metabolic functions are not yet fully understood [53]. Apart from its well-established role in maintaining fluid-electrolyte homeostasis, albumin may also have immunomodulatory properties [54]. Circulating albumin interacts with various inflammatory mediators, thereby promoting neutrophil degranulation and enhancing phagocytic activity [55]. ...
Purpose
This study aimed to evaluate the correlation between hypoalbuminemia upon admission and the incidence of postoperative urinary tract infections (UTIs) in elderly patients with hip fractures.
Methods
A retrospective analysis was performed on the medical records of elderly patients who underwent surgical treatment for hip fractures at a level I trauma center from 2013 to 2023. Serum albumin levels were measured upon admission, and hypoalbuminemia was defined as a total albumin level < 35 g/L. Multivariable logistic regression and propensity score matching analysis were utilized to control and reduce potential confounding factors, aiming to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CI) for UTIs to determine the strength of the association.
Results
This observational cohort study included 1279 patients, among whom 298 (23.3%) developed UTIs. Patients with albumin levels < 35 g/L had significantly greater odds of developing UTIs compared to those with albumin levels ≥ 35 g/L (OR 1.86, 95% CI 1.28–2.70). Further analysis, dividing albumin levels into quartiles, demonstrated that patients in the Q 2 group (38.0–40.9 g/L; OR 1.38, 95% CI 0.88–2.17), Q 3 group (35.0–37.9 g/L; OR 1.69, 95% CI 1.06–2.71), and Q 4 group (15.3–34.9 g/L; OR 2.67, 95% CI 1.61–4.43) had notably higher odds of developing UTIs compared to those in the Q 1 group (41.0–52.0 g/L).
Conclusions
The presence of hypoalbuminemia upon admission in elderly patients undergoing hip fracture surgery is strongly correlated with the occurrence of postoperative UTIs. Furthermore, this association exhibits a clear dose–response relationship.
... It is well-acknowledged that serum albumin concentration may be an indicator of individual nutritional status [27,28], with lower values indicating a decrease in protein reserve, stimulating catabolic processes that lead to muscle breakdown [29]. There is also a body of research indicating the antioxidant properties of albumin, showing that albumin is a specific modulator of cellular glutathione, one of the body's major antioxidants [30]. Oxidative damage may play a crucial role in skeletal muscle decline with aging. ...
Epidemiological and public health resonance of sarcopenia in late life requires further research to identify better clinical markers useful for seeking proper care strategies in preventive medicine settings. Using a machine-learning approach, a search for clinical and fluid markers most associated with sarcopenia was carried out across older populations from northern and southern Italy. A dataset of adults >65 years of age (n = 1971) made up of clinical records and fluid markers from either a clinical-based subset from northern Italy (Pavia) and a population-based subset from southern Italy (Apulia) was employed (n = 1312 and n = 659, respectively). Body composition data obtained by dual-energy X-ray absorptiometry (DXA) were used for the diagnosis of sarcopenia, given by the presence of either low muscle mass (i.e., an SMI < 7.0 kg/m2 for males or
... With regard to the characteristic of antioxidants, serum albumin contains a free cysteine at the − 34 position, called the Cys34 residue, which has redox properties [44]. With this, serum albumin inhibits lipid peroxidation [45] and increases glutathione levels [46], acting as an anti-atherogenic agent. With regard to the characteristic of anticoagulation, albumin Cys-34 binds nitric oxide, resulting in the formation of nitrosoalbumin, which prolongs the biological activity of nitric oxide, acting as a vasodilator and inhibitor of platelet aggregation agent [47]. ...
Background
Patients with coronary artery disease (CAD) combined with diabetes have a higher risk of cardiovascular events, and high-sensitivity C-reactive protein (hs-CRP)-to-albumin ratio (CAR) is a novel inflammatory biomarker. However, whether the CAR can identify high-risk patients with CAD and type 2 diabetes (T2DM) remains unclear.
Methods
The present study was based on a prospective and observational cohort with 10,724 individuals who undergo percutaneous coronary intervention (PCI) in Fu Wai Hospital throughout the year 2013 consecutively enrolled. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. CAR was calculated with the formula: hs-CRP (mg/L)/albumin (g/L). According to the optimal cut-off value of CAR for all-cause mortality, patients were divided into higher CAR (CAR-H) and lower CAR (CAR-L) groups.
Results
A total of 2755 patients with T2DM who underwent PCI and received dual antiplatelet therapy were finally enrolled. During a follow-up of 5 years (interquartile range: 5.0–5.1 years), 126 (4.6%) all-cause mortalities and 74 (2.7%) cardiac mortalities were recorded. In the multivariable Cox model, CAR-H was associated with a higher risk of all-cause mortality (hazard ratio [HR]: 1.634, 95% confidence interval [CI] 1.121–2.380, p = 0.011) and cardiac mortality (HR: 1.733, 95% CI 1.059–2.835, p = 0.029) compared with CAR-L. When comparing the predictive value, CAR was superior to hs-CRP for all-cause mortality (area under the curve [AUC] 0.588 vs. 0.580, p = 0.002) and cardiac mortality (AUC 0.602 vs. 0.593, p = 0.004).
Conclusion
In this real-world cohort study, a higher level of CAR was associated with worse 5-year outcomes among diabetic patients with PCI.
... 24 Studies have found that sALB may exert anti-inflammatory effects by specifically regulating cellular glutathione (GSH) levels and reducing TNF-α-mediated activation of nuclear factor kappa B (NF-κB). 25 Additionally, sALB inhibits NF-κB activation in a GSH-independent manner, thereby inhibiting TNF-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression and monocyte adhesion, exerting anti-inflammatory effects on vascular endothelial cells. 26 Oxidative stress and inflammation are key factors in patients with T2DM with concurrent DR and DKD. ...
Objective:
To analyze the associations between serum albumin (sALB) level and diabetic microvascular complications, including diabetic retinopathy (DR) and diabetic kidney disease (DKD), in patients with type 2 diabetes mellitus (T2DM).
Methods:
This retrospective study included 951 hospitalized patients with T2DM who had completed screening for DR and DKD during hospitalization. Patients were divided into three groups according to sALB tertiles. Multivariate logistic regression analysis was used to assess the association of sALB with microvascular complications.
Results:
The prevalence of DR, DKD and macroalbuminuria increased with decreasing sALB levels. Multivariate logistic regression analysis showed that lower levels of sALB (Q1) were associated with higher risk of DR (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.12-2.26), DKD (OR: 3.00, 95% CI: 2.04-4.41) and macroalbuminuria (OR: 9.76, 95% CI: 4.62-20.63) compared with higher levels of sALB (Q3) after adjustment for other risk factors. After stratification by sex and age, the effect of lower levels of sALB (Q1) on DR incidence was more obvious in patients with male (OR: 1.60, 95% CI: 1.00-2.56), and aged<65 years (OR: 1.74, 95% CI: 1.14-2.65) (P < 0.05 for all); the effect of lower levels of sALB (Q1) on the incidence of DKD was significant in both males (OR: 3.78, 95% CI: 2.26-6.32) and females (OR: 2.35, 95% CI: 1.26-4.35) (P < 0.05 for all), while only the age <65 years (OR: 3.46, 95% CI: 2.16-5.53) was significant in the age subgroup (P < 0.001).
Conclusion:
Decreased sALB levels may be an independent risk indicator of DR and DKD in patients with T2DM, and significantly associated with DKD progression. For DR screening, special attention should be paid to men aged <65 years, while screening for DKD should pay attention to people <65 years old.
... Транспортування екзогенних та ендогенних сполук тривалий час розглядалось як головна функція сироваткового альбуміну [4]. Згодом були визначені інші важливі функції, такі як антиоксидантні властивості [5], здатність бути депо для оксиду азоту (NO) [6,7], регуляція рівня глутатіону, активація ядерного фактора каппа в клітинах [8], які, проте, пов'язані з його здатністю зв'язувати низькомолекулярні сполуки [9]. Середній час існування альбуміну в крові становить до 25 діб, проте взаємодія з ушкоджуючими факторами знижує час його циркуляції [10]. ...
Мета дослідження – вивчення взаємодій пропоксазепаму та деяких похідних 1,4-бенздіазепіну з людським сироватковим альбуміном методом молекулярного докінгу та аналіз складових цих взаємодій.Молекулярний докінг було проведено за допомогою програми iGEMDOCK v2.1, структури альбуміну (з діазепамом (2BXF) та ібупрофеном (2BXG)) отримані з бази даних біологічних макромолекул (http://www.rcsb.org/). Структури лігандів (діазепам, оксазепам, пропоксазепам, 3-гідроксипропоксазепам, ібупрофен) оптимізовано за величиною внутрішньої енергії в програмі Avogadro (v 1.2.0) і наведено у форматі *.pdb. Візуалізацію результатів докінгу виконано з використанням ресурсу ezCADD.Сполуки демонструють перехресну спорідненість до сайтів зв’язування, але більш схильні до взаємодії з бенздіазепіновим місцем зв’язування, при цьому енергія зв’язування пропоксазепаму (– 10,27 ккал/моль) є найбільшою серед досліджуваних структур і навіть перевищує цей показник для діазепаму. Розраховані в процесі молекулярного докінгу характеристики зв’язування відповідають реальним, але з частковим завищенням даних для діазепамового сайту.За результатами молекулярно докінгу до діазепамового та ібупрофенового сайтів зв’язування людського сироваткового альбуміну з референтними сполуками – діазепамом та ібупрофеном – було встановлено, що сполуки демонструють перехресну спорідненість до сайтів зв’язування, хоча діазепам демонструє більше значення енергії взаємодії (– 9,38 ккал/моль) з власним сайтом, ніж з ібупрофеновим (– 7,32 ккал/моль).Енергія зв’язування з діазепамовим сайтом для пропоксазепаму (– 10,27 ккал/моль) є найбільшою серед досліджуваних структур і навіть перевищує цей показник для діазепаму, а його положення відрізняється утворенням зв’язків з атомом брому (положення «7») на відміну від діазепаму, який взаємодіє через кисень карбонільної групи гетерокільця. В ібупрофеновому місці зв’язування пропоксазепам явно взаємодіє з іншім сайтом, але зі спільними амінокислотними залишками.
... 22 The best-known function of albumin is that of maintaining the oncotic pressure of the plasma, 5,23-25 but it has other effects such as: facilitating the metabolism, transport and solubilisation of molecules; antioxidant and immunomodulatory effects; stabilising capillary permeability and the vascular endothelium; and fulfilling other functions which promote homeostasis ( Figure 5). 19,21,24,[26][27][28][29][30][31][32][33] ...
Cirrhosis is characterized by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Proinflammatory cytokines and pro-oxidant molecules are key in the development of organ dysfunction. Cirrhosis progression and worsening of portal hypertension bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic Inflammation. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic, and endothelial stabilizing properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options, capable of targeting several physiopathological aspects of cirrhosis. For the elaboration of the present manuscript on the uses of albumin in liver cirrhosis, several experts in the field of hepatology in Mexico were divided into 5 working groups to summarise and formulate, when appropriate, position statements: 1)pathophysiology of cirrhosis and properties of albumin; 2)proven uses of albumin [large-volume paracentesis, spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS)]; 3)controversial/emerging uses of albumin (long-term use, acute decompensation, liver transplant, non-HRS kidney injury, muscle cramps, non-SBP infections, hyponatremia, encephalopathy); 4)use of albumin in acute-on-chronic liver failure, immunomodulation, and systemic Inflammation; 5)pharmacoeconomics.
... Yeh et al. performed a retrospective study of 252 adult patients receiving enteral nutrition in a surgical intensive care unit, and found that serum albumin had a negative association with proinflammatory cytokines, such as C-reactive protein (CRP), white blood cell, and especially NLR [30]. Experiments showed that albumin could protect cells against oxidant injury and control inflammatory through specifically regulating levels of cellular glutathione (GSH) and decreasing TNF-α-induced activation of NF-kappaB [31]. In human aortic endothelial cells, Zhang et al. also reported that physiological albumin levels selectively inhibited the expression of vascular cell adhesion molecule-1 induced by TNF-ɑ in a GSH-independent manner [32]. ...
Background
Previous studies that explored the relationship of serum albumin with diabetic peripheral neuropathy (DPN) have indicated inconsistent results. Thus, the present study aimed to evaluated the association between serum albumin and DPN, defined as vibration perception threshold (VPT) values ≥ 25 V and/or inability to feel the monofilament, in Chinese patients with type 2 diabetes mellitus (T2DM).
Methods
1465 T2DM patients aged ≥ 16 years, who completed the measurement of serum albumin and DPN screening between 2012 and 2015, were included in the cross-sectional study. Correlation and multivariate logistic regression analysis models were used to evaluate the possible relationship between serum albumin and DPN.
Results
Patients with higher quartiles of serum albumin had significantly lower VPT values and prevalence of DPN compared with those with lower quartiles ( P for trend < 0.01), and there was an inverse relationship between serum albumin and VPT values and prevalence of DPN (all P < 0.01). Multivariate logistic regression analysis demonstrated that the risk of DPN was progressively decreased across serum albumin quartiles ( P for trend < 0.01), and participants in the highest quartile of serum albumin were at a significantly decreased risk of DPN compared to those in the lowest quartile (odds rate: 0.311, 95% confidence intervals 0.134–0.724, P < 0.01). ROC analysis revealed that the optimal cutoff point of serum albumin for the prevalence of DPN was 39.95 g/L in patients with T2DM, with a sensitivity of 65.88% and a specificity of 66.7%.
Conclusions
Decreased levels of serum albumin might be correlated with increased risk of DPN in Chinese patients with T2DM. Future longitudinal studies with large samples are warranted to confirm our findings, and elucidate putative mechanisms for the association.
