IL-1ß Induces LDL Transcytosis by a Novel Pathway Involving LDLR and Rab27a.

BACKGROUND: In early atherosclerosis, circulating LDLs (low-density lipoproteins) traverse individual endothelial cells by an active process termed transcytosis. The CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) treated advanced atherosclerosis using a blocking antibody for IL-1ß (interleukin-1ß); this significantly reduced cardiovascular events. However, whether IL-1ß regulates early disease, particularly LDL transcytosis, remains unknown. METHODS: We used total internal reflection fluorescence microscopy to quantify transcytosis by human coronary artery endothelial cells exposed to IL-1ß. To investigate transcytosis in vivo, we injected wild-type and knockout mice with IL-1ß and LDL to visualize acute LDL deposition in the aortic arch. RESULTS: Exposure to picomolar concentrations of IL-1ß induced transcytosis of LDL but not of albumin by human coronary artery endothelial cells. Surprisingly, expression of the 2 known receptors for LDL transcytosis, ALK-1 (activin receptor-like kinase-1) and SR-BI (scavenger receptor BI), was unchanged or decreased. Instead, IL-1ß increased the expression of the LDLR (LDL receptor); this was unexpected because LDLR is not required for LDL transcytosis. Overexpression of LDLR had no effect on basal LDL transcytosis. However, knockdown of LDLR abrogated the effect of IL-1ß on transcytosis rates while the depletion of Cav-1 (caveolin-1) did not. Since LDLR was necessary but overexpression had no effect, we reasoned that another player must be involved. Using public RNA sequencing data to curate a list of Rab (Ras-associated binding) GTPases affected by IL-1ß, we identified Rab27a. Overexpression of Rab27a alone had no effect on basal transcytosis, but its knockdown prevented induction by IL-1ß. This was phenocopied by depletion of the Rab27a effector JFC1 (synaptotagmin-like protein 1). In vivo, IL-1ß increased LDL transcytosis in the aortic arch of wild-type but not Ldlr-/- or Rab27a-deficient mice. The JFC1 inhibitor nexinhib20 also blocked IL-1ß-induced LDL accumulation in the aorta. CONCLUSIONS: IL-1ß induces LDL transcytosis by a distinct pathway requiring LDLR and Rab27a; this route differs from basal transcytosis. We speculate that induction of transcytosis by IL-1ß may contribute to the acceleration of early disease.

Walnut Jug r 1 is Responsible for Primary Sensitization among Patients Suffering Walnut-Hazelnut 2S Albumin Cross-Reactivity.

Walnut and hazelnut coallergy is a frequent manifestation in clinical practice whose molecular basis remains unclear. For this purpose, walnut-hazelnut cross-reactivity was evaluated in 20 patients allergic to one or both tree nuts and sensitized to their 2S albumins. Immunoblotting assays showed that 85% of patients recognized Jug r 1, walnut 2S albumin, which was associated with the development of severe symptoms; 50% of them corecognized hazelnut 2S albumin, Cor a 14. Both allergens were isolated using chromatographic techniques. Inhibition ELISAs revealed that Jug r 1 strongly inhibited the binding of Cor a 14-specific IgE, but Cor a 14 only partially inhibited Jug r 1-specific IgE binding. Our results showed that patients sensitized to walnut/hazelnut 2S albumins were not a homogeneous population. There were patients sensitized to specific epitopes of walnut 2S albumins and patients sensitized to cross-reactive epitopes between walnut and hazelnut, with Jug r 1 being the primary sensitizer.

Angiogenesis outcomes of metformin utilization in diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: To review relevant literature regarding the role of metformin in angiogenesis among diabetic patients. METHODS: The systematic review and meta-analysis conducted from May to September 2022, and comprised search on Medline, ScienceDirect, ProQuest, Web of Science, EBSCOhost and Cochrane Library databases. The studies included were published in the English language and were human studies having angiogenesis endothelial markers as the outcomes of interest among patients of type 2 diabetes mellitus undergoing metformin therapy. Endothelial markers, including vascular endothelial growth factor, von-Willebrand-factor, plasminogen activator inhibitor-1, soluble vascular adhesion molecule- 1, intercellular adhesion molecule-1, soluble endothelialselectin, tissue plasminogen activator, urinary albumin excretion, platelet endothelial cell adhesion molecule-1 and thrombin-activatable fibrinolysis inhibitor, were assessed as angiogenesis outcomes. Data was statistically analysed using Review Manager 5.4. RESULTS: Of the 413 studies identified, 8(1.9%) were included; 5(62.5%) randomised control trials, 2(25.0%) cross-sectional, and 1(12.5%) cohort studies, with overall 1199 patients. Among the outcomes, von-Willebrandfactor (p=0.01), soluble vascular adhesion molecule-1 (p<0.00001), intercellular adhesion molecule-1 (p=0.0003), soluble endothelial-selectin (p=0.007), and tissue plasminogen activator (p<0.00001) showed significantly lower levels after metformin treatment using the random effect methods. CONCLUSIONS: Metformin was found to have an additional effect of endothelial function improvement.

Predictive nomogram of high-risk patients with active tuberculosis in latent tuberculosis infection.

INTRODUCTION: The absence of predictive models for early latent tuberculosis infection (LTBI) progression persists. This study aimed to create a screening model to identify high-risk LTBI patients prome to active tuberculosis (ATB) reactivation. METHODOLOGY: Patients with confirmed ATB were enrolled alongside LTBI individuals as a reference, with relevant clinical data gathered. LASSO regression cross-validation reduced data dimensionality. A nomogram was developed using multiple logistic regression, internally validated with Bootstrap resampling. Evaluation included C-index, receiver operating characteristic (ROC) curve, and calibration curves, with clinical utility assessed through decision curve analysis. RESULTS: The final nomogram incorporated serum albumin (OR = 1.337, p = 0.046), CD4+ (OR = 1.010, p = 0.004), and CD64 index (OR = 0.009, p = 0.020). The model achieved a C-index of 0.964, an area under the ROC curve of 0.962 (95% CI: 0.926-0.997), sensitivity of 0.971, and specificity of 0.910. Internal validation showed a mean absolute error of 0.013 and 86.4% identification accuracy. The decision curve indicated substantial net benefit at a risk threshold exceeding 10% (1: 9). CONCLUSIONS: This study established a biologically-rooted nomogram for high-risk LTBI patients prone to ATB reactivation, offering strong predictability, concordance, and clinical value. It serves as a personalized risk assessment tool, accurately identifying patients necessitating priority prophylactic treatment, complementing existing host risk factors effectively.

Structural evolution of pea-derived albumins during pH and heat treatment studied with light and X-ray scattering.

Pea albumins are found in the side stream during the isolation of pea proteins. They are soluble at acidic pH and have functional properties which differ from their globulin counterparts. In this study, we have investigated the aggregation and structural changes occurring to pea albumins under different environmental conditions, using a combination of size-exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALS) and small-angle X-ray scattering (SAXS). Albumins were extracted from a dry fractionated pea protein concentrate by precipitating the globulin fraction at acidic pH. The albumins were then studied at different pH (3, 4, 4.5, 7, 7.5, and 8) values. The effect of heating at 90 °C for 1, 3, and 5 min on their structural changes was investigated using SAXS. In addition, size exclusion of the albumins showed 4 distinct populations, depending on pH and heating conditions, with two large aggregates peaks (∼250 kDa): a dimer peak (∼24 kDa) containing predominantly pea albumin 2 (PA2), and a monomer peak of a molar mass of about 12 kDa (PA1). X-ray scattering intensities as a function of q were modeled as polydisperse spheres, and their aggregation was followed as a function of heating time. Albumins was most stable at pH 3, showing no aggregation during heat treatment. While albumins at pH 7.5 and 8 showed aggregation after heating, solutions at pH 4, 4.5, and 7 already contained aggregates even before heating. This work provides new knowledge on the overall structural development of albumins under different environmental conditions, improving our ability to employ these as future ingredients in foods.

Distribution of Traditional Chinese Medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study.

OBJECTIVE: To analyze the distribution of Traditional Chinese medicine (TCM) syndromes in patients with diabetic kidney disease (DKD) and its related factors. METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical Center, Chinese PLA General Hospital from April 2020 to August 2021. Analysis of their TCM syndromes and related factors was carried out. RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease (CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome, and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend; the differences were statistically significant (P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio (OR) = 1.022, P = 0.005], albumin (OR = 1.058, P = 0.006), and estimated glomerular filtration rate (eGFR) (OR = 1.020, P < 0.001) but negatively correlated with male sex (OR = 0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin (OR = 1.056, P < 0.001) and eGFR (OR = 1.008, P = 0.022) but negatively correlated with age (OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age (OR = 1.028, P = 0.021) and glycosylated hemoglobin (OR = 1.223, P = 0.007) but negatively correlated with total cholesterol (OR = 0.792, P = 0.006). Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin (OR = 0.977, P < 0.001), albumin (OR = 0.891, P < 0.001), and eGFR (OR = 0.978, P < 0.001) but positively correlated with high density lipoprotein (OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both Qi and Yin, liver-kidney Yin, and spleen-kidney Yang deficiency syndromes. TCM syndromes were correlated with laboratory test results.

Study on phosphonylation and modification characteristics of organophosphorus nerve agents on multi-species and multi-source albumins.

Protein adducts are vital targets for exploring organophosphorus nerve agents (OPNAs) exposure and identification, that can be used to characterize the chemical burden and initiate chemical safety measures. However, the use of protein adducts as biomarkers of OPNA exposure has developed slowly. To further promote the development of biomarkers in chemical forensics, it is crucial to expand the range of modified peptides and active sites, and describe the characteristics of OPNA adducts at specific reaction sites. This study utilized multi-species and multi-source albumins as the protein targets. We identified 56 peptides in albumins from various species (including human, horse, rat and pig), that were modified by at least two OPNAs. Diverse modification characteristics were observed in response to certain agents: including (1) multiple sites on the same peptide modified by one or more agents, (2) different reactivities at the same site in homologous albumins, and (3) different preferences at the same active sites associated with differences in the biological matrix during exposure. Our studies provided an empirical reference with rationalized underpinnings supported by estimated conformation energetics through molecular modeling. We employed different peptide markers for detection of protein adducts, as (one would do) in forensic screening for identification and quantification of chemical damage. Three characteristic peptides were screened and analyzed in human albumin, including Y287ICENQDSISSK, K438VPQVS443TPTLVEVSR, and Y162LY164EIAR. Stable fragment ions with neutral loss were found from their tandem MS/MS spectra, which were used as characteristic ions for identification and extraction of modified peptides in enzymatic digestion mixtures. Coupling these observations with computer simulations, we found that the structural stability of albumin and albumin-adduct complexes (as well as the effective force that promotes stability of different adducts) changes in the interval before and after adduct formation. In pig albumin, five active peptides existed stably in vivo and in vitro. Most of them can be detected within 30 min after OPNA exposure, and the detection window can persist about half a month. These early findings provided the foundation and rationale for utilizing pig albumin as a sampling target for rapid analysis in future forensic work.

Inhibition of Human Colorectal Cancer by a Natural Product 7-Acetylhorminone and Interactions with BSA/HSA: Multispectral Analysis and In Silico and In Vitro Studies.

We have semi-synthesized a natural product 7-acetylhorminone from crude extract of Premna obtusifolia (Indian headache tree), which is active against colorectal cancer after probation through computational screening methods as it passed through the set parameters of pharmacokinetics (most important nonblood-brain barrier permeant) and drug likeliness (e.g., Lipinski's, Ghose's, Veber's rule) which most other phytoconstituents failed to pass combined with docking with EGFR protein which is highly upregulated in the colorectal carcinoma cell. The structure of 7-acetylhorminone was confirmed by single crystal X-ray diffraction studies and 1H NMR, 13C NMR, and COSY studies. To validate the theoretical studies, first, in vitro experiments were carried out against human colorectal carcinoma cell lines (HCT116) which revealed the potent cytotoxic efficacy of 7-acetylhorminone and verified preliminary investigation. Second, the drugability of 7-acetylhorminone interaction with serum albumin proteins (HSA and BSA) is evaluated both theoretically and experimentally via steady-state fluorescence spectroscopic studies, circular dichroism, isothermal titration calorimetry, and molecular docking. In summary, this study reveals the applicability of 7-acetylhorminone as a potent drug candidate or as a combinatorial drug against colorectal cancer.

Correlation of Neutrophil-Lymphocyte and Albumin-Globulin Ratios With Outcomes in Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy or Upfront Surgery.

PURPOSE: Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer. METHODS: This retrospective study included all patients with stage I-III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore. Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests. RESULTS: A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13-3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16-0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17-0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07-2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11-3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36-0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09-2.44; p = 0.018). CONCLUSION: NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.

Erbium(III) complexes with fluoroquinolones: Structure and biological properties.

Four erbium(III) complexes with the fluoroquinolones enrofloxacin, levofloxacin, flumequine and sparfloxacin as ligands were synthesized and characterized by a wide range of physicochemical and spectroscopic techniques as well as single-crystal X-ray crystallography. The compounds were evaluated for their activity against the bacterial strains Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Xanthomonas campestris, which was higher than that of the corresponding free quinolones. The interaction mode of the complexes with calf-thymus DNA is via intercalation, as suggested by diverse studies such as UV-vis spectroscopy, DNA-viscosity measurements and competitive studies with ethidium bromide. Fluorescence emission spectroscopy revealed the high affinity of the complexes for bovine and human serum albumin and the determined binding constants suggested a tight and reversible binding of the compounds with both albumins.

Dansyl-tagged xanthate ester as a capping agent to synthesize fluorescent silver nanoparticles with binding affinity toward serum albumin.

Developing multifunctional nanomaterials with distinct photochemical properties, such as high quantum yield, improved photostability, and good biocompatibility is critical for a wide range of biomedical applications. Motivated by this, we designed and synthesized a dansyl-tagged xanthate-based capping agent (DX) for the synthesis of fluorescent silver nanoparticles (AgNPs). The capping agent DX was characterized by 1H and 13C-NMR, LC-MS, and FT-IR. The synthesized DX-capped fluorescent AgNPs were thoroughly characterized by UV-visible spectroscopy, fluorescence spectroscopy, field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), dynamic light scattering (DLS), and zeta potential. The fluorescent AgNPs showed distinct surface plasmon resonance absorption at λmax = 414 nm, fluorescence at λmax = 498 nm, quantum yield = 0.24, zeta potential = +18.6 mV, average size = 18.2 nm. Furthermore, the biological activity of the fluorescent AgNPs was validated by its interaction with the most abundant protein in the blood, that is, BSA (Bovine serum albumin) and HSA (Human serum albumin) with binding constant of 2.34 × 104 M-1 and 2.14 × 104 M-1 respectively. Interestingly, fluorescence resonance energy transfer (FRET) was observed between the fluorescent AgNPs and BSA/HSA with a FRET efficiency of 77.23% and 56.36%, respectively, indicating strong interaction between fluorescent AgNPs and BSA/HSA.

Human amniotic epithelial cells (HAECS); a potential cell type for the hepatic disorders.

OBJECTIVE: To isolate a homogenous population of human amniotic epithelial cells (hAECs) from the amniotic membrane of the human placenta and differentiate them into hepatic-like cells with the help of small molecules. METHODS: hAECs were isolated by using the enzymatic digestion method and characterized for the presence of specific stem cell markers. In-vitro, hepatic differentiation of hAECs was carried out by using a combination of small molecules. Differentiated cells were observed under a live cell imaging microscope for morphological changes followed by gene and protein expression analysis by qPCR and immunocytochemistry respectively. RESULTS: The isolated hAECs attained characteristic cuboid epithelial shape and express stem cells marker. The hepatic differentiation method was optimized based on soluble chemical compounds supplied in the culture medium. The differentiated hAECs phenotypically acquire hepatic-like cell features and expressed hepatic markers as well as hepatic protein albumin at immature levels. CONCLUSIONS: The isolated population of hAECs is highly proliferative. Moreover, hepatic markers expression in the isolated hAECs makes them an exclusive source for the treatment of chronic liver diseases.

Albumin Levels and Risk of Early Cardiovascular Complications After Ischemic Stroke: A Propensity-Matched Analysis of a Global Federated Health Network.

BACKGROUND: No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke. METHODS: Retrospective analysis with a federated research network (TriNetX) based on electronic medical records (International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching. RESULTS: Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels. CONCLUSIONS: Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation.

Pharmacokinetics/pharmacodynamics analysis and establishment of optimal dosing regimens using unbound cefmetazole concentration for patients infected with Extended-Spectrum ß-lactamase producing Enterobacterales (ESBL-E).

STUDY OBJECTIVE: Establish methods for measuring cefmetazole (CMZ) concentrations conduct a pharmacokinetic/pharmacodynamic (PK/PD) analysis using unbound CMZ concentrations for extended-spectrum ß-lactamase producing enterobacterales (ESBL-E) and investigate optimal dosing regimens for not undergoing hemodialysis (non-HD) and undergoing hemodialysis (HD) patients. DESIGN: Prospective observational study. PATIENTS: Included patients treated with CMZ who provided written informed consent and were admitted to the Tokyo Bay Urayasu Ichikawa Medical Center between August 2021 and July 2022. MEASUREMENTS: Total and Unbound CMZ concentration was measured by high-performance liquid chromatography (HPLC) with solid-phase extraction and ultrafiltration. SETTING: Determining the CMZ dosing regimen involved modified creatinine clearance (CLCR ) with measured body weight (BW) using the Cockcroft-Gault equation. For non-HD patients, blood samples were collected during at least three points. For patients undergoing HD, 1 g was administered via intravenous infusion, or rapid intravenous injection after HD, or 30 min before the end of HD. Blood samples were collected before HD (pre-HD), and 1 and 3 h after starting HD and post-HD. All blood samples were collected at steady-state. Patient information was collected from electronic medical records. An unbound PK model was constructed for the non-HD patients. A nomogram was constructed using Monte Carlo simulations with a 90% probability of target attainment at 70% free time above the minimum inhibitory concentration (MIC). For the HD patients, a nomogram was used to determine the optimal dosing regimen for each HD schedule. MAIN RESULTS: CMZ measurement methods were established. A model analysis of unbound PK in 37 non-HD patients incorporated creatinine clearance (CLCR ) using the Cockcroft-Gault equation, albumin (ALB) for clearance and body weight (BW) for the volume of distribution. In Monte Carlo simulations, nomograms corresponding to the MIC (known and unknown) were generated for each covariate. Using the nomogram, non-HD patients with an ESBL-E MIC of 8 mg/L, a BW of 60 kg, an ALB of 25 g/L, and a CLCR of 60 mL/min required administration of 2 g every 6 h (1- and 3-h infusions). Unbound PK model parameters were calculated for 7 HD patients, and the optimal dosing regimens following PK/PD were determined for each HD schedule. In HD patients, the regimen after and during HD was established using a treatment that was effective up to an ESBL-E MIC of 4 mg/L. CONCLUSIONS: The nomogram for CMZ regimens established by PK/PD analysis of measured CMZ concentrations enables optimal CMZ dosing for ESBL-E-infected patients.

Molecular interactions and binding dynamics of Alpelisib with serum albumins: insights from multi-spectroscopic techniques and molecular docking.

Alpelisib (ALP) is a potent anti-cancer drug showing promising activity against advanced breast cancers. Hence, profound understanding of its binding dynamics within the physiological system is vital. Herein, we have investigated interaction of ALP with human serum albumin (HSA) and bovine serum albumin (BSA) using spectroscopic techniques like absorption, fluorescence, time-resolved, synchronous and 3D-fluorescence, FRET, FT-IR, CD, and molecular docking studies. The intrinsic fluorescence of both BSA and HSA quenched significantly by ALP with an appreciable red shift in its emission maxima. Stern-Volmer analysis showed increase in Ksv with temperature indicating involvement of dynamic quenching process. This was further validated by no significant change in absorption spectrum of BSA and HSA (at 280 nm) upon ALP interaction, and by results of fluorescence time-resolved lifetime studies. ALP exhibited moderately strong binding affinity with BSA (of the order 106 M-1) and HSA (of the order 105 M-1), and the major forces accountable for stabilizing the interactions are hydrophobic forces. Competitive drug binding experiments and molecular docking suggested that ALP binds to site I in subdomain IIA of BSA and HSA. The Förster distance r was found to be less than 8 nm and 0.5 Ro < r < 1.5 Ro which suggests possible energy transfer between donors BSA/HSA and acceptor ALP. Synchronous and 3D-fluoresecnce, FT-IR and CD studies indicated that ALP induces conformational changes of BSA and HSA upon interaction.Communicated by Ramaswamy H. Sarma.

Albumin, an interesting and functionally diverse protein, varies from 'native' to 'effective' (Review).

Human serum albumins (HSAs) are synthesized in the liver and are the most abundant proteins in plasma of healthy human. They play an important role in the pathophysiological processes of the liver and even the whole organism. Previous studies have mainly focused on the regulation of HSAs' expression. However, with the progress of research in recent years, it has been found that the content of circulating albumin cannot fully reflect the biological function of albumin itself. Given the aforementioned fact, the concept of serum 'effective albumin concentration' has been proposed. It refers to the content of albumin that is structurally and functionally intact. Alterations in the molecular structure and function of albumin have been reported in a variety of diseases, including liver disease. Moreover, these changes have been verified to affect the progression of oxidative stress­related diseases. However, the link between albumin structure and function has not been fully elaborated, and the mechanisms by which different forms of albumin affect disease also need to be further investigated. In this context, the present review mainly expounded the biological characteristics and functions of albumin, summarized the different types of post­translational modification of albumin, and discussed their functional changes and possible mechanisms in non­alcoholic fatty liver disease, alcoholic hepatitis, viral hepatitis and different stages of cirrhosis. This will help to improve understanding of the role of albumin in disease development and provide a more comprehensive physiological basis for it in disease treatment.

The Role of Procalcitonin/Albumin Ratio and CRP/Albumin Ratio in Predicting In-hospital Mortality in COVID-19 Patients.

Background: Hospitalized coronavirus disease 2019 (COVID-19) patients have higher mortality rates. Parameters to predict mortality are needed. Therefore, we investigated the power of procalcitonin/albumin ratio (PAR) and C-reactive protein/albumin ratio (CAR) to predict in-hospital mortality in hospitalized COVID-19 patients. Methods: In this study, 855 patients were included. Patients' PAR and CAR values were recorded from the hospital information management system. The patients were evaluated in two groups according to their in-hospital mortality status. Results: In-hospital mortality was observed in 163 patients (19.1%). The median PAR and CAR values of patients in the non-survivor group were statistically significantly higher than those of patients in the survivor group, PAR (median: 0.07, interquartile range [IQR]: 0.03-0.33 vs. median: 0.02, IQR: 0.01-0.04, respectively; p < 0.001); CAR (median: 27.60, IQR: 12.49-44.91 vs. median: 7.47, IQR: 2.66-18.93, respectively; p < 0.001). The area under the curve (AUC) and odds ratio (OR) values obtained by PAR to predict in-hospital mortality were higher than the values obtained by procalcitonin, CAR, albumin, and CRP (AUCs of PAR, procalcitonin, CAR, albumin, and CRP: 0.804, 0.792, 0.762, 0.755, and 0.748, respectively; OR: PAR > 0.04, procalcitonin > 0.14, CAR > 20.59, albumin < 4.02, and CRP > 63; 8.215, 7.134, 5.842, 6.073, and 5.07, respectively). Patients with concurrent PAR > 0.04 and CAR > 20.59 had an OR of 15.681 compared to patients with concurrent PAR < 0.04 and CAR < 20.59. Conclusions: In this study, PAR was found to be more valuable for predicting in-hospital COVID-19 mortality than all other parameters. In addition, concurrent high levels of PAR and CAR were found to be more valuable than a high level of PAR or CAR alone.

Evaluating the effect of cow's milk fortified with albumin powder on malnutrition and anthropometric indices in primary-school children with mild-to-moderate underweight: A randomized double-blinded clinical trial.

Background: A proper diet plan is one of the necessary conditions for maintaining the children's health. The aim of this study was to evaluate the effect of consumption of pasteurized cow's milk fortified with albumin protein in primary-school children, in Yasuj, Iran. Materials and Methods: In this double-blind randomized clinical trial with 12 weeks of duration, 60 children aged 7-13 years, mild to moderate underweight (-1≥ weight-for-age z-score ≥-3), were randomly assigned to control and albumin groups. The albumin group and the control group received 200 cc of milk with 10 g of albumin powder and 200 cc of milk with 10 g of cornstarch powder, respectively. At the beginning and end of the study, food intake and anthropometric indices were measured. Results: After 12 weeks of intervention, none of the anthropometric indices (weight, weight-for-age z-score, body mass index (BMI), BMI-for-age z-score, and waist circumference) showed significant changes as compared to baseline in the control group, but weight-for-age z-score and BMI-for-age z-score showed significant increase as compared to baseline in the albumin group (before: -2.25 ± 0.40, after: -1.98 ± 0.35, P = 0.001 and before: -3.48 ± 0.86, after: -3.06 ± 0.71, P = 0.009, respectively). The comparison of the mean changes between the two groups showed significant difference regarding weight-for-age z-score (control group: -1.70 ± 0.31 in comparison with albumin group: -1.98 ± 0.35, P = 0.002), BMI (control group: 12.08 ± 1.96 in comparison with albumin group: 12.13 ± 1.49, P = 0.03), and BMI-for-age z-score (control group: -3.11 ± 0.91 in comparison with albumin group: -3.06 ± 0.71, P = 0.02). Conclusion: The consumption of albumin powder with milk can improve weight-for-age z-score and BMI-for-age z-score indices in children with mild-to-moderate underweight. Larger controlled interventional studies with longer duration are recommended.

Alanine Scanning of the Unstructured Region of Ara h 2 and of a Related Mimotope Reveals Critical Amino Acids for IgE Binding.

SCOPE: The unstructured region of Ara h 2, referred to as epitope 3, contains a repeated motif, DYPSh (h = hydroxyproline) that is important for IgE binding. METHODS AND RESULTS: IgE binding assays to 20mer and shorter peptides of epitope 3, defines a 16mer core sequence containing one copy of the DPYSh motif, DEDSYERDPYShSQDP. This study performs alanine scanning of this and a related 12mer mimotope, LLDPYAhRAWTK. IgE binding, using a pool of 10 sera and with individual sera, is greatly reduced when alanine is substituted for aspartate at position 8 (D8; p < 0.01), tyrosine at position 10 (Y10; p < 0.01), and hydroxyproline at position 12 (h12; p < 0.001). IgE binding to alanine-substituted peptides of a mimotope containing the DPY_h motif confirm the critical importance of Y (p < 0.01) and h (p < 0.01), but not D. Molecular modeling of the core and mimotope suggests an h-dependent conformational basis for the recognition of these sequences by polyclonal IgE. CONCLUSIONS: IgE from pooled sera and individual sera differentially bound amino acids throughout the sequences of Epitope 3 and its mimotope, with Y10 and h12 being most important for all sera. These results are highly significant for designing hypoallergenic forms of Ara h 2.

Neutral and cationic nickel(II) complexes with substituted salicylaldehydes: Characterization, antibacterial activity, and interaction with biomacromolecules.

Four neutral and six cationic nickel(II) complexes of the substituted salicylaldehydes (X-diCl-saloH), namely 3,5-dichloro-salicylaldehyde (3,5-diCl-saloH) and 5-fluoro-salicylaldehyde (5-F-saloH), were synthesized in the absence or presence of the N,N'-donors 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc), or 2,2'-bipyridylamine (bipyam) as co-ligands and were characterized by various techniques. The obtained complexes bear the general formulas [Ni(X-salo)2(H2O)2], [Ni(3,5-diCl-salo)2(neoc/phen)] and [Ni(X-salo)(N,N'-donor)2](PF6). The crystal structures of three complexes were determined by single-crystal X-ray crystallography revealing a bidentate coordination of the salicylaldehydes. The interaction of the compounds with calf-thymus DNA was studied by diverse techniques which revealed an intercalative interaction for the neutral complexes [Ni(X-salo)2(H2O)2] and [Ni(3,5-diCl-salo)2(neoc/phen)]and the co-existence of electrostatic interactions for the cationic complexes [Ni(X-salo)(N,N'-donor)2](PF6). The compounds bind tightly and reversibly to serum albumins. The antibacterial activity of the compounds was investigated against Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli NCTC 29,212 and Xanthomonas campestris ATCC 1395 and the complexes bearing neoc as co-ligand proved the most potent.