Search Results (84)

Background: Alpha-1-acid glycoprotein (AGP) is a glycoprotein synthesized mainly by the liver. Nonalcoholic fatty liver disease (NAFLD) and liver fibrosis (LF) are associated with metabolic disorders. The aim of this study was to examine the potential correlation between AGP and both NAFLD and LF. Methods: The data were derived from the 2017–2023 National Health and Nutrition Examination Survey (NHANES). The linear association between AGP and NAFLD and LF was examined by multivariate logistic regression models. Non-linear relationships were described by fitting smoothed curves and threshold effect analysis. Subgroup analysis was also performed to assess potential regulatory factors. Results: The study included 2270 females. AGP was found to be significantly and positively associated with NAFLD [OR = 12.00, 95% CI (6.73, 21.39), p < 0.001] and LF [OR = 2.20, 95% CI (1.07, 4.50), p = 0.042]. Furthermore, the association between AGP and NAFLD was significantly different in the diabetic subgroup (p < 0.05 for interaction). Additionally, we found an inverted U-shaped relationship between AGP and controlled attenuation parameter (CAP), with an inflection point at 1.20 g/L. Conclusions: We found a significant positive correlation between AGP and both NAFLD and LF, and there was an inverted U-shaped relationship between AGP and CAP. Full article

Introduction. The pathophysiology of Pyoderma Gangrenosum (PG) involves altered innate and adaptive immunity, mutagenic and epigenetic changes, the autoinflammatory state, and the overexpression of cytokines. This study investigated the potential contribution of inflammation, redox signaling, and the immune system in the pathogenesis of PG. Materials and Methods. This case–control study included 36 patients with PG and 30 controls. We have determined the serum concentrations of acute phase proteins (C-reactive protein—CRP, alpha1 glycoprotein acid—AGPA, Albumin), interleukin-17A -IL-17A, β2 microglobulin-β2MG, reduced glutathione-GSH, oxidized glutathione- GSSG, the GSH/GSSG ratio, and hematological parameters (white blood cells-WBC, neutrophil-lymphocyte ratio-NLR, erythrocyte sedimentation rate-ESR) in patients with PG compared with controls. Furthermore, we have evaluated the variations in these markers before and after treatment in PG patients. Results. The serum concentrations of acute phase proteins (CRP, AGPA, and Albumin) and the IL-17A, β2MG, GSH, GSSG, and GSH/GSSG ratio were significantly different between the PG group and controls. Hematological parameters (WBC, NLR, and ESR), acute phase proteins (CRP, AGPA, and albumin), and IL-17A showed an exaggerated and persistent inflammatory response in patients with PG. In patients with PG associated with systemic diseases, the dysregulation of the biochemical events was more severe. Conclusions. The acute phase proteins, β2MG-MHC class I complex, and the GSH-GSSG system are unbalanced in PG. Our results could improve the diagnosis and our understanding of the pathogenic basis of PG. Full article

Preclinical evidence suggests that short chain fatty acids (SCFAs) produced by gut microbiota may impact body composition and muscle growth. While aging is implicated in negative alterations to the gut microbiome, exercise may mitigate these changes. Limited human evidence indicates that resistance training (RT) does not appreciably alter the gut microbiome in older adults, and no human study has examined whether resistance training differentially alters the gut microbiome and associated SCFAs between younger and older individuals. Therefore, we examined whether 10 weeks of RT differentially altered fecal microbiota composition, fecal and circulating SCFAs, and serum markers associated with gastrointestinal integrity in two cohorts of adults. Fecal and serum samples were obtained from untrained younger (22 ± 2 years, n = 12) and older (58 ± 8 years, n = 12) participants prior to and following 10 weeks of supervised twice-weekly full-body RT. Outcome measures immediately before (PRE) and after the intervention (POST) included dual X-ray absorptiometry for body composition, ultrasound for vastus lateralis (VL) thickness, 16S rRNA gene sequencing fecal microbiome data, serum and fecal SCFAs measured by gas chromatography, and serum intestinal fatty acid-binding protein 2 (FABP2), lipopolysaccharide-binding protein (LBP), and leucine-rich alpha-2 glycoprotein (LRG-1) quantified by enzyme-linked immunosorbent assays. Main effects and interactions were measured by repeated measures analysis of variance (group × time; G × T) for all dependent variables, and Spearman correlations were used to explore relationships among changes in relevant outcomes. The intervention significantly increased VL thickness and lean body mass (p < 0.05) equally in both groups. Although group differences in microbiome beta diversity were identified, no effects of age, time, or their interaction were observed for the alpha diversity measures. Seven SCFAs were detected in the fecal samples, albeit no significant age, time, or interaction effects were evident. In serum, acetic acid was the only SCFA detected, with no significant age, time, or interaction effects. Serum LRG1 decreased for all participants (p = 0.007) with higher levels in younger adults (p = 0.015), but no G × T interactions were observed for this marker, serum FABP2, or LBP. No significant correlations were observed among RT-induced changes in muscle mass-related outcomes and changes in fecal microbiome diversity, total or individual SCFAs, or serum FABP2/LBP/LRG-1. These results highlight that 10 weeks of RT largely does not affect fecal microbiota, associated SCFAs, or select markers of gastrointestinal integrity in untrained younger or older adults. Full article

Background/Objectives: Ropivacaine is primarily metabolized by the liver. High doses of ropivacaine, combined with altered pharmacokinetics due to hepatectomy, raise concerns about potential drug toxicity. We investigated the impact of LMH (laparoscopic major hepatectomy) on the pharmacokinetics of high-dose ropivacaine. Methods: Ten patients undergoing LMH received a BD-TAP (bilateral dual transversus abdominis plane) block with a high dose of ropivacaine (3 mg·kg⁻¹ in 60 mL). Plasma concentrations of total and free ropivacaine and AAG (alpha-1 acid glycoprotein) levels were measured. Liver volumes were calculated using three-dimensional liver reconstruction technology. Results: The peak total ropivacaine concentration occurred 45 min after the block, reaching 2031.5 (876.0) ng·mL⁻¹, with a tendency to exceed the toxicity threshold in patients with a CFLV (cut functional liver volume) exceeding 199.24 mL or a CFLV/TFLV (total functional liver volume) ratio surpassing 18.61%. The peak free ropivacaine concentration, 111.5 (31.3) ng·mL⁻¹, was observed 90 min after the block, potentially exceeding the toxicity threshold when CFLV exceeded 452.33 mL or the CFLV/TFLV ratio was greater than 42.16%. Plasma AAG levels increased approximately 1.5 times within 24 h, from 1519.7 (422.6) μg·mL⁻¹ preoperatively to 2253.6 (460.4) μg·mL⁻¹ postoperatively, effectively reducing the toxicity risk associated with free ropivacaine. Conclusions: Preoperative administration of high-dose ropivacaine can be safely utilized in patients undergoing major hepatectomy. The increased plasma AAG concentration due to surgical stress reduces free ropivacaine levels, enhancing patient tolerance to the drug. The CFLV and CFLV/TFLV ratio may be supplementary indicators for predicting ropivacaine toxicity. Full article

Cisplatin combined with gemcitabine, a doublet regimen, is the first-line treatment for patients with advanced lung adenocarcinoma (ADC); however, the treatment response remains poor. This study aimed to identify potential biomarkers for predicting response to cisplatin and gemcitabine. Tissue transcriptome and blood proteome analyses were conducted on 27 patients with lung ADC. Blood-derived proteins that reflected tissue-specific biomarkers were obtained using Venn diagrams. The candidate proteins were validated by Western blotting. Lentivirus-mediated short hairpin RNA interference was used to verify the functional roles of the candidate proteins in human A549 cells. We identified 417 differentially expressed genes, including 52 upregulated and 365 downregulated genes, and 31 differentially expressed proteins, including 26 upregulated and 5 downregulated proteins. Integrative analysis revealed the presence of alpha-1-acid glycoprotein 1 (A1AG1) and fibrinogen alpha chain (FGA or FIBA) in both the tissue and serum. FGA levels were elevated in responders compared to non-responders, and reduced serum FGA levels were correlated with resistance to this regimen. Moreover, FGA knockdown in A549 cells resulted in resistance to the doublet regimen. Our findings indicate that FGA is a tissue-specific serum protein that may function as a blood-based biomarker to predict the response of patients with lung ADC to cisplatin plus gemcitabine chemotherapy. Full article

Background/Objectives: Pathophysiological variability in patients with cancer is associated with differences in responses to pharmacotherapy. In this work, we aimed to describe the demographic characteristics and hematological, biochemical, and coagulation variables in a large oncology cohort and to develop, optimize, and provide open access to modeling equations for the estimation of variables potentially relevant in pharmacokinetic modeling. Methods: Using data from 1793 patients with cancer, divided into training (n = 1259) and validation (n = 534) datasets, a modeling network was developed and used to simulate virtual oncology populations. All analyses were conducted in RStudio 4.3.2 Build 494. Results: The simulation network based on sex, age, biogeographic origin/ethnicity, and tumor type (fixed or primary factors) was successfully validated, able to predict age, height, weight, alpha-1-acid glycoprotein, albumin, hemoglobin, C-reactive protein and lactate dehydrogenase serum levels, platelet–lymphocyte and neutrophil–lymphocyte ratios, and hematocrit. This network was then successfully extrapolated to simulate the laboratory variables of eight oncology populations (n = 1200); only East Asians, Sub-Saharan Africans, Europeans, only males, females, patients with an ECOG performance status equal to 2, and only patients with pancreas cancer or ovarian cancer. Conclusions: this network constitutes a valuable tool to predict relevant characteristics/variables of patients with cancer, which may be useful in the evaluation and prediction of pharmacokinetics in virtual oncology populations, as well as for model-based optimization of oncology treatments. Full article

Glycan structures of glycoproteins and glycolipids on the surface glycocalyx and luminal sugar layers of intracellular membrane compartments in human cells constitute a key interface between intracellular biological processes and external environments. Sialic acids, a class of alpha-keto acid sugars with a nine-carbon backbone, are frequently found as the terminal residues of these glycoconjugates, forming the critical components of these sugar layers. Changes in the status and content of cellular sialic acids are closely linked to many human diseases such as cancer, cardiovascular, neurological, inflammatory, infectious, and lysosomal storage diseases. The molecular machineries responsible for the biosynthesis of the sialylated glycans, along with their biological interacting partners, are important therapeutic strategies and targets for drug development. The purpose of this article is to comprehensively review the recent literature and provide new scientific insights into the mechanisms and therapeutic implications of sialylation in glycoproteins and glycolipids across various human diseases. Recent advances in the clinical developments of sialic acid-related therapies are also summarized and discussed. Full article

Cardiovascular disease (CVD) may be inherited, as recently shown with the identification of single nucleotide polymorphisms (SNPs or “snips”) on a 250 kb DNA fragment that encodes 92 proteins associated with CVD. CVD is also triggered by microbial dysbiosis, microbial metabolites, metabolic disorders, and inflammatory intestinal epithelial cells (IECs). The epithelial cellular adhesion molecule (Ep-CAM) and trefoil factor 3 (TFF3) peptide keeps the gut wall intact and healthy. Variations in Ep-CAM levels are directly linked to changes in the gut microbiome. Leptin, plasminogen activator inhibitor 1 (PAI1), and alpha-1 acid glycoprotein 1 (AGP1) are associated with obesity and may be used as biomarkers. Although contactin 1 (CNTN1) is also associated with obesity and adiposity, it regulates the bacterial metabolism of tryptophan (Trp) and thus appetite. A decrease in CNTN1 may serve as an early warning of CVD. Short-chain fatty acids (SCFAs) produced by gut microbiota inhibit pro-inflammatory cytokines and damage vascular integrity. Trimethylamine N-oxide (TMAO), produced by gut microbiota, activates inflammatory Nod-like receptors (NLRs) such as Nod-like receptor protein 3 (NLRP3), which increase platelet formation. Mutations in the elastin gene (ELN) cause supra valvular aortic stenosis (SVAS), defined as the thickening of the arterial wall. Many of the genes expressed by human cells are regulated by gut microbiota. The identification of new molecular markers is crucial for the prevention of CVD and the development of new therapeutic strategies. This review summarizes the causes of CVD and identifies possible CVD markers. Full article

The enantioselective binding of three proton pump inhibitors (PPIs)—omeprazole, rabeprazole, and lansoprazole—to two key plasma proteins, α1-acid glycoprotein (AGP) and human serum albumin (HSA), was characterized. The interactions between PPI enantiomers and proteins were investigated using a multifaceted analytical approach, including high-performance liquid chromatography (HPLC), fluorescence and UV spectroscopy, as well as in silico molecular docking. HPLC analysis demonstrated that all three PPIs exhibited enantioseparation on an AGP-based chiral stationary phase, suggesting stereoselective binding to AGP, while only lansoprazole showed enantioselective binding on the HSA-based column. Quantitatively, the S-enantiomers of omeprazole and rabeprazole showed higher binding affinity to AGP, while the R-enantiomer of lansoprazole displayed greater affinity for AGP, with a reversal in the elution order observed between the two protein-based columns. Protein binding percentages, calculated via HPLC, were greater than 88% for each enantiomer across both transport proteins, with all enantiomers displaying higher affinity for AGP compared to HSA. Thermodynamic analysis indicated that on the HSA, the more common, enthalpy-controlled enantioseparation was found, while in contrast, on the AGP, entropy-controlled enantioseparation was observed. The study also identified limitations in using fluorescence titration due to the high native fluorescence of the compounds, whereas UV titration was effective for both proteins. The determined logK values were in the range of 4.47–4.83 for AGP and 4.02–4.66 for HSA. Molecular docking supported the experimental findings by revealing the atomic interactions driving the binding process, with the predicted enantiomer elution orders aligning with experimental data. The comprehensive use of these analytical methods provides detailed insights into the enantioselective binding properties of PPIs, contributing to the understanding of their pharmacokinetic differences and aiding in the development of more effective therapeutic strategies. Full article

Objective: Prostate tumors, if prostate cancer or adenoma, represent a major public health challenge. Progress in research on inflammation has revealed a connection between inflammation, immunity, and cancer. In this context, this study aimed to find IL-6 signaling systemic abnormalities in the inflammatory tumor microenvironment. Material and methods: This study was case–controlled, multicentered, and included 86 patients, 43 diagnosed with BPH and 43 diagnosed with PCa, between January 2019 and January 2020. The study group was homogenous and the studied parameters were IL-6 complex (IL-6, soluble receptor IL-6R, soluble glycoprotein gp130), acute phase proteins (C reactive protein—CRP, acid alpha1 glycoprotein—AGPA, ferritin, albumin, transferrin), and oxidative stress-associated variables (malondialdehyde—MDA, carbonylated protein—PCO, 8-hydroxy-deoxy guanosine-8-OHdG, total antioxidant status—bTAS). Results: The inflammatory microenvironment determined IL-6 signaling alterations (over-regulation of sIL-6R and suppression of sgp130 in PCa versus BPH), changes in acute phase reaction markers (increased serum levels of CRP, AGPA, ferritin, and decreased serum levels of albumin, transferrin) that were much more evident in PCa compared to BPH, an imbalance between macromolecular oxidative damage (MDA, PCO, 8-OHdG) and endogenous antioxidants (TAS) that was more accentuated in PCa compared with BPH, and a representative association between the sIL-6R/sgp130 ratio and inflammatory/oxidative stress-related factors only in PCa patients. Conclusions: Our study reconfirms the anterior concept that IL-6 promotes prostatic tumorigenesis. In this study, we first demonstrated that a high sIL-6R/sgp130 ratio facilitates prostate malignancy. Full article

Background: Alcohol-related brain degeneration (ARBD) is associated with cognitive–motor impairments that can progress to disability and dementia. White matter (WM) is prominently targeted in ARBD due to chronic neurotoxic and degenerative effects on oligodendrocytes and myelin. Early detection and monitoring of WM pathology in ARBD could lead to therapeutic interventions. Objective: This study examines the potential utility of a non-invasive strategy for detecting WM ARBD using exosomes isolated from serum. Comparative analyses were made with paired tissue (Tx) and membrane vesicles (MVs) from the temporal lobe (TL). Methods: Long Evans rats were fed for 8 weeks with isocaloric liquid diets containing 37% or 0% caloric ethanol (n = 8/group). TL-Tx, TL-MVs, and serum exosomes (S-EVs) were used to examine ethanol’s effects on oligodendrocyte glycoprotein, astrocyte, and oxidative stress markers. Results: Ethanol significantly decreased the TL-Tx expression of platelet-derived growth factor receptor alpha (PDGFRA), 2′,3′-cyclic nucleotide 3′ phosphodiesterase (CNPase), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), glial fibrillary acidic protein (GFAP), and 8-OHdG, whereas in the TL-MVs, ethanol increased CNPase, PDGFRA, and 8-OHdG, but decreased MOG and GFAP concordantly with TL-Tx. Ethanol modulated the S-EV expression by reducing PLP, nestin, GFAP, and 4-hydroxynonenal (HNE). Conclusion: Chronic ethanol exposures differentially alter the expression of oligodendrocyte/myelin, astrocyte, and oxidative stress markers in the brain, brain MVs, and S-EVs. However, directionally concordant effects across all three compartments were limited. Future studies should advance these efforts by characterizing the relationship between ABRD and molecular pathological changes in brain WM-specific exosomes in serum. Full article

Background and Objectives: This study investigated whether serum alpha-1-acid glycoprotein (AGP) at diagnosis could reflect the cross-sectional activity represented by the Birmingham vasculitis activity score (BVAS) and further predict poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 70 patients with AAV. Clinical data at diagnosis, including AAV-specific indices and acute-phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were reviewed. All-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were evaluated as poor outcomes of AAV. Serum AGP was measured using the sera obtained and stored at diagnosis. Results: The median age of the patients was 63.0 years, with 29 male and 41 female patients. The median serum AGP was 150.9 μg/mL. At diagnosis, serum AGP was significantly correlated with BVAS and ESR but not CRP or serum albumin. Additionally, serum AGP showed significant correlations with the sum scores of ear–nose–throat and pulmonary manifestations; however, no significant differences in serum AGP according to each poor outcome were observed. Although serum AGP at diagnosis tended to be associated with ESKD occurrence during follow-up, serum AGP at AAV diagnosis was not significantly useful in predicting the future occurrence of poor outcomes of AAV during follow-up. Conclusions: In this study, we demonstrated the clinical utility of serum AGP at AAV diagnosis in assessing the cross-sectional activity represented by BVAS in patients with AAV for the first time. Full article

Protein-energy wasting and inflammation are major risk factors for complications in hemodialysis patients. As these risk factors are triggered by a pro-inflammatory state, oxidative stress and hemodynamic dysfunction, which overlap in hemodialyzed subjects, we aimed to assess the efficacy of a cost-effective and straightforward screening tool, the Prognostic Inflammatory and Nutritional Index (PINI), in regularly screening maintenance hemodialysis (MHD) patients, to detect early signs of inflammation and malnutrition. A 12-month follow-up was carried out on a cohort of 102 adult patients undergoing maintenance dialysis, during which the Prognostic Inflammatory and Nutritional Index (PINI) was calculated using the formula alpha1-Acid Glycoprotein (AGP) × C-reactive protein (CRP)/albumin (ALB) × transthyretin (TTR). A PINI score < 1 was considered normal. The patients were stratified based on their PINI score: 66 patients (64.70%) had a normal score, below 1, while 36 patients (35.30%) had a PINI score ≥ 1. Despite the absence of clinical evidence of inflammation at enrollment, the latter group exhibited higher levels of CRP. During the follow-up period, all patients with a PINI score ≥ 1 experienced at least one acute event, compared to only 6% of patients with a normal PINI score, which presented COVID-19 infection as an acute event. The evaluation of the PINI can effectively identify the silent malnutrition–inflammation syndrome and predict the risk of acute events. This straightforward test appears to be a rapid tool that is independent of the examiner’s experience and subjectivity, thereby potentially reducing hospitalization costs. Full article

Until recently, the diagnosis of feline infectious peritonitis (FIP) in cats usually led to euthanasia, but recent research has revealed that antiviral drugs, including the nucleoside analog GS-441524, have the potential to effectively cure FIP. Alpha-1-acid glycoprotein (AGP) has been suggested as a diagnostic marker for FIP. However, AGP quantification methods are not easily accessible. This study aimed to establish a Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL^TM) assay on the VetBio-1 analyzer to determine the AGP concentrations in feline serum and effusion samples. Linearity was found in serial dilutions between 1:2000 and 1:32,000; the intra-run and inter-run precision was <5% and <15%, respectively; and AGP was stable in serum stored for at least 8 days at room temperature, at 4 °C and at −20 °C. Cats with confirmed FIP had significantly higher serum AGP concentrations (median: 2954 µg/mL (range: 200–5861 µg/mL)) than those with other inflammatory diseases (median: 1734 µg/mL (305–3449 µg/mL)) and clinically healthy cats (median 235 µg/mL (range: 78–616 µg/mL); p_KW < 0.0001). The AGP concentrations were significantly higher in the effusions from cats with FIP than in those from diseased cats without FIP (p_MWU < 0.0001). The AGP concentrations in the serum of cats with FIP undergoing GS-441524 treatment showed a significant drop within the first seven days of treatment and reached normal levels after ~14 days. In conclusion, the VetBio-1 SPARCL^TM assay offers a precise, fast and cost-effective method to measure the AGP concentrations in serum and effusion samples of feline patients. The monitoring of the AGP concentration throughout FIP treatment provides a valuable marker to evaluate the treatment’s effectiveness and identify potential relapses at an early stage. Full article

Background: Alpha-1 acid glycoprotein (AGP) may support a clinical diagnosis of feline infectious peritonitis (FIP). In this study, we assessed the analytical and diagnostic performances of a novel ELISA method to measure feline AGP. Methods: AGP was measured in sera and effusions from cats with FIP (n = 20) or with other diseases (n = 15). Precision was calculated based on the coefficient of variation (CV) of repeated testing, and accuracy was calculated by linearity under dilution (LUD). Results: The test is precise (intra-assay CVs: <6.0% in individual samples, <15.0% in pooled samples; inter-assay CVs <11.0% and <15.0%) and accurate (serum LUD r²: 0.995; effusion LUD r²: 0.950) in serum and in effusions. AGP is higher in cats with FIP than in other cats in both serum (median: 1968, I-III interquartile range: 1216–3371 μg/mL and 296, 246–1963 μg/mL; p = 0.009) and effusion (1717, 1011–2379 μg/mL and 233, 165–566 μg/mL; p < 0.001). AGP discriminates FIP from other diseases (area under the receiver operating characteristic curve: serum, 0.760; effusion, 0.877), and its likelihood ratio is high (serum: 8.50 if AGP > 1590 μg/mL; effusion: 3.75 if AGP > 3780 μg/mL). Conclusion: This ELISA method is precise and accurate. AGP in serum and in effusions is a useful diagnostic marker for FIP. Full article