ASSESSMENT OF ACUTE PHASE PROTEINS AND PROTEIN ELECTROPHORESIS IN HEALTHY GIBBONS (HYLOBATIDAE) IN MANAGED SETTINGS.

Acute phase proteins (APP) and protein electrophoresis (EPH) offer crucial insights into inflammation and overall health in various species. In this study, we validated serum amyloid A (SAA) and C-reactive protein (CRP) reagents for use with serum samples from gibbons (Hylobatidae, n = 50), spanning five species across four gibbon genera: eastern hoolock (Hoolock leuconedys), Javan (Hylobates moloch), pileated (Hylobates pileatus), siamang (Symphalangus syndactylus), and white-cheeked (Nomascus leucogenys). Preliminary reference intervals (n = 50) were calculated for SAA (1.8-48.1 mg/L), CRP (0.1-11.1 mg/L), and EPH via capillary zone electrophoresis, in healthy gibbons. Comparing clinically normal (n = 38) and abnormal (n = 12) individuals, significant differences were observed in the albumin/globulin ratio (P = 0.0003), prealbumin (P = 0.0345), and albumin (P = 0.0094), with abnormal individuals exhibiting statistically significantly higher γ-globulins (P = 0.0224), SAA (P = 0.0001), and CRP (P = 0.0003). Despite significant chromosomal rearrangements among different gibbon species, we found no statistically significant differences of SAA and CRP levels across species. However, some differences between species were observed in EPH fractions. This study presents the first report of the evaluation of APP and EPH in gibbons, underscoring the potential use of these biomarkers in gibbon health monitoring. Further research with larger sample sizes of both normal and abnormal gibbons is recommended to solidify the clinical utility of these biomarkers in these species.

Diagnostic utility of acute phase proteins and their ability to guide antibiotic usage in pigs, horses, and cattle: a mapping review.

To mitigate the use of antibiotics for many of the multifactorial diseases seen in pigs, horses and cattle, new diagnostic tools are needed. Acute phase protein (APP) measurements can, in humans, be used to guide antibiotic treatment initiation, evaluate treatment efficacy, and make a prognosis. The aim of this review is to collect evidence on the clinical functionality of APP measurements as a tool to guide antibiotic treatment in pigs, horses, and cattle. Literature was retrieved using Medline, CAB Abstracts and Google Scholar. The acute phase response has been investigated for a plethora of diseases and clinical signs and the major acute phase proteins are elevated in diseased compared to healthy animals. Few studies correlated acute phase response with aetiology, antibiotic treatment efficacy, prognosis, or severity of disease. The existing research does not support that APP can be used to guide antibiotic treatment, but the reported studies indicate that C-reactive protein (CRP) might be able to differentiate between bacterial and non-bacterial causes of disease in pigs. Serum amyloid A (SAA) might reflect underlying aetiology in horses and infectious or non-infectious cases of mastitis in cows.

Dynamics of changes in proteins of the acute phase of inflammation in the postoperative period in patients with disseminated peritonitis.

OBJECTIVE: Aim: To determine the effect of the developed complex treatment of patients with peritonitis on the dynamics of humoral factors of nonspecific reactivity in the course of the disease. PATIENTS AND METHODS: Materials and Methods: The study included 124 patients with toxic and terminal stages of peritonitis, who were divided into 3 groups. Group I (main) included 39 patients whose complex treatment included cytochrome C. Group II (main) included 41 patients whose complex treatment included cytochrome C and a solution containing levocarnitine and arginine hydrochloride. The comparison group comprised 44 patients who did not receive the specified drugs. The patients underwent determination of the levels of fibronectin, ceruloplasmin, and procalcitonin in the serum during the course of the disease. RESULTS: Results: In patients of the I and II main groups, the use of the proposed treatment contributed to the optimization of the production of acute phase proteins: a decrease in procalcitonin production during the study, optimization of ceruloplasmin and fibronectin production, especially in the II main group. In patients of the comparison group, decompensation in the production of humoral inflammatory factors was determined, associated with a significant increase in fibronectin production, a decrease in ceruloplasmin content, and an increase in procalcitonin throughout the entire period. CONCLUSION: Conclusions: The use of cytochrome C and a solution containing levocarnitine and arginine hydrochloride in the complex treatment of patients with disseminated peritonitis helps to optimize the production of acute phase proteins, which leads to a decrease in inflammation and the preservation of factors of nonspecific humoral activity at a subcompensated level.

Acute-phase proteins as indicators of disease severity and mortality in COVID-19 patients.

The aim of the study was to conduct of relationship of acute-phase proteins (APPs) with the severity of COVID-19 defined by National Institutes of Health and according to the criteria of MEWS scale, with the presence of a cytokine storm, oxygen therapy and patient survival. We enrolled 96 patients with COVID-19 and 30 healthy people. The samples were taken on the day of admission and after 9 days on average. Not only commonly used APPs such as CRP, procalcitonin and ferritin and also rarely assayed proteins such as transferrin, haptoglobin, α1-acid glycoprotein and α1-antitrypsin, were tested in the study. The levels of APPs depends on the severity of COVID-19 disease, on the presence of cytokine storm and used oxygen therapy. The greatest APPs changes occurred in the most advanced form of the disease, with the presence of a cytokine storm and the most intense oxygen therapy. The results obtained from MEWS scale were not consistent with National Institutes of Health scores. Studies in the second samples showed the quenching of the acute phase reactions and the effectiveness of oxygen therapy. Only two of the examined APPs i.e. procalcitonin and transferrin, differed between surviving and non-surviving patients, and these two predispose to the role of prognostic factors in Covid-19. In conclusion, the concentration of not all acute-phase proteins depends on the severity of COVID-19 disease, presence of cytokine storm, the used of oxygen therapy and only some of them (procalcitonin and transferrin) are related to the survival outcomes. Of the newly tested acute-phase proteins, only transferrin shows significance as a marker of disease severity and mortality in COVID-19 disease.

Urinary cystatin-C and urinary NGAL associated with sepsis predicts longer hospital stay in premature newborns.

Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30 days (odds ratio: 1.052; 95% CI: 1.012-1.093; p = 0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.

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Intestinal fatty acid binding protein is associated with infarct size and cardiac function in acute heart failure following myocardial infarction.

BACKGROUND: In acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into circulation and contribute to inflammation and adverse cardiac remodelling. We aimed to investigate gut leakage markers and their associations with inflammation, infarct size and cardiac function. METHODS: We examined 61 ST-elevation myocardial infarction (STEMI) patients who developed acute HF within 48 hours of successful percutaneous coronary intervention (PCI). Serial blood samples were taken to measure lipopolysaccharide (LPS), LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14) and intestinal fatty acid binding protein (I-FABP). Cumulative areas under the curve (AUCs) from baseline to day 5 were calculated. Serial echocardiography was performed to assess left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and wall motion score index (WMSI). Single-photon emission CT (SPECT) was performed at 6 weeks to determine infarct size and LVEF. RESULTS: I-FABPAUC correlated positively with infarct size (rs=0.45, p=0.002), GLS (rs=0.32, p=0.035) and WMSI (rs=0.45, p=0.002) and negatively with LVEF measured by SPECT (rs=-0.40, p=0.007) and echocardiography (rs=-0.33, p=0.021) at 6 weeks. LPSAUC, LBPAUC and sCD14AUC did not correlate to any cardiac function marker or infarct size. Patients, who at 6 weeks had above median GLS and WMSI, and below-median LVEF measured by SPECT, were more likely to have above median I-FABPAUC during admission (adjusted OR (aOR) 5.22, 95% CI 1.21 to 22.44; aOR 5.05, 95% CI 1.25 to 20.43; aOR 5.67, 95% CI 1.42 to 22.59, respectively). The same was observed for patients in the lowest quartile of LVEF measured by echocardiography (aOR 9.99, 95% CI 1.79 to 55.83) and three upper quartiles of infarct size (aOR 20.34, 95% CI 1.56 to 264.65). CONCLUSIONS: In primary PCI-treated STEMI patients with acute HF, I-FABP, a marker of intestinal epithelial damage, was associated with larger infarct size and worse cardiac function after 6 weeks.

Serum markers of microbial translocation and intestinal damage in assessment of gastrointestinal tract involvement in systemic sclerosis.

Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score "moderate-to-very severe" [OR 1.001 (CI 95%: 1.001-1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023-1.506), p < 0.05] as variables associated with UCLA distension/bloating "moderate-to-very severe". The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea "moderate-to-very severe" [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms.

The Potential of Eight Plasma Proteins as Biomarkers in Redefining Leptospirosis Diagnosis.

Leptospirosis, a notifiable endemic disease in Malaysia, has higher mortality rates than regional dengue fever. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study investigated the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion compared with dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The iTRAQ analysis identified a total of 450 proteins, which were refined to a list of 290 proteins through a series of exclusion criteria. Differential expression in the plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins, which are apolipoprotein A-II (APOA2), C-reactive protein (CRP), fermitin family homolog 3 (FERMT3), leucine-rich alpha-2-glycoprotein 1 (LRG1), lipopolysaccharide-binding protein (LBP), myosin-9 (MYH9), platelet basic protein (PPBP), platelet factor 4 (PF4), profilin-1 (PFN1), serum amyloid A-1 protein (SAA1), and thrombospondin-1 (THBS1). Following a study on a verification cohort, a panel of eight plasma protein biomarkers was identified for potential leptospirosis diagnosis: CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. In conclusion, a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the "one disease, one biomarker" concept.

Alterations in plasma proteome during acute COVID-19 and recovery.

BACKGROUND: The severe course of COVID-19 causes cardiovascular injuries, although the mechanisms involved are still not fully recognized, linked, and understood. Their characterization is of great importance with the establishment of the conception of post-acute sequelae of COVID-19, referred to as long COVID, where blood clotting and endothelial abnormalities are believed to be the key pathomechanisms driving circulatory system impairment. METHODS: The presented study investigates temporal changes in plasma proteins in COVID-19 patients during hospitalization due to SARS-CoV-2 infection and six months after recovery by targeted SureQuant acquisition using PQ500 panel. RESULTS: In total, we identified 167 proteins that were differentially regulated between follow-up and hospitalization, which functionally aggregated into immune system activation, complement and coagulation cascades, interleukins signalling, platelet activation, and extracellular matrix organization. Furthermore, we found that temporal quantitative changes in acute phase proteins correlate with selected clinical characteristics of COVID-19 patients. CONCLUSIONS: In-depth targeted proteome investigation evidenced substantial changes in plasma protein composition of patients during and recovering from COVID-19, evidencing a wide range of functional pathways induced by SARS-CoV-2 infection. In addition, we show that a subset of acute phase proteins, clotting cascade regulators and lipoproteins could have clinical value as potential predictors of long-term cardiovascular events in COVID-19 convalescents.

Cytokine and acute-phase proteins response following vaccination against infectious bronchitis in broilers.

BACKGROUND: Infectious bronchitis (IB) is an important disease of poultry, and vaccination is the best method of preventing IB in the poultry industry worldwide. OBJECTIVES: This study was designed to evaluate cytokine and acute-phase protein (APP) responses and their correlations with antibody titres following vaccination regimes against IB in the broiler. MATERIALS AND METHODS: Broilers were vaccinated with H120 and 1/96 vaccine strains, and MIX (H120 + 1/96) vaccine strains on Days 0 and 14. Heterophils/lymphocyte (H/L) ratio, APPs including chicken serum amyloid A (SAA), chicken pentraxin 3 (chPTX3), chicken interleukin 1ß (IL-1ß), chicken interleukin 6 (IL-6) levels and antibody titres were measured. RESULTS: An increase in the H/L ratio, SAA, chPTX3, IL-1ß and IL-6 levels in vaccinated groups was observed 1 day after the first (highest rates) and second (lower levels) vaccination up to 3 days in three different patterns and then started to decrease. The results showed an immediate, short-lived response and moderate increases in all criteria. Changing patterns of APPs were different but in similar pattern after the first and second immunization in vaccinated groups. A positive correlation between all criteria values on Days 1 and 15 with antibody titres on Day 28 may indicate agonistic cross-regulation. CONCLUSION: Different types of IB vaccines could induce different patterns of APPs responses, which can be used to evaluate immune response outcomes in vaccine design, development and administration. The IL-6 with the highest increase can be a sensitive parameter and chPTX3 with the high increase could be an important criterion.

Gut microbiota dysbiosis deteriorates immunoregulatory effects of tryptophan via colonic indole and LBP/HTR2B-mediated macrophage function.

Tryptophan (Trp) has been shown to regulate immune function by modulating gut serotonin (5-HT) metabolism and signaling. However, the mechanisms underlying the microbial modulation of gut 5-HT signaling in gut inflammation with gut microbiota dysbiosis require further investigation. Here, we investigated the effects of Trp supplementation on the composition and metabolism of the gut microbiome and 5-HT signaling-related gut immune function using a dextran sodium sulfate (DSS)-induced colitis mouse model coupled with antibiotic exposure. The results showed that antibiotic treatment before but not during DSS treatment decreased the immunoregulatory effects of Trp and aggravated gut inflammation and body weight loss in mice. Metagenomic analysis revealed that the fecal microbiota transplantation of Trp-enriched gut microbiota to recipient mice subject to antibiotic pre-exposure and DSS treatment alleviated inflammation by increasing the relative abundances of Lactobacillus and Parabacteroides and the microbial production of indole coupled with the activation of the 5-HT receptor 2B (HTR2B) in the colon. Transcriptomic analysis showed that HTR2B agonist administration strengthened the beneficial effects of Trp in DSS-induced colitis mice with antibiotic exposure by reducing gut lipopolysaccharide-binding protein (LBP) production, IκB-α/nuclear factor-κB signaling, and M1 macrophage polarization. Indole treatment reduced LBP production and M1 macrophage polarization both in mice with DSS-induced colitis and in lipopolysaccharide-treated mouse macrophages; however, the HTR2B antagonist reversed the effects of indole. Our findings provide the basis for developing new dietary and therapeutic interventions to improve gut microbiota dysbiosis-associated inflammatory gut disorders and diseases.

Characterization of Inflammation/Immune-, Acute Phase-, Extracellular Matrix-, Adhesion-, and Serine Protease-Related Proteins in the Amniotic Fluid of Women With Early Preterm Prelabor Rupture of Membranes.

PROBLEM: To determine whether altered concentrations of various inflammation/immune-, acute phase-, extracellular matrix-, adhesion-, and serine protease-related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM). METHOD OF STUDY: This was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24-31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme-linked immunosorbent assay (ELISA): APRIL, DKK-3, Gal-3BP, IGFBP-2, IL-8, VDBP, lumican, MMP-2, MMP-8, SPARC, TGFBI, TGF-ß1, E-selectin, ICAM-5, P-selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA. RESULTS: Multivariate logistic regression analyses revealed that (i) elevated APRIL, IL-8, MMP-8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF-ß1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL-8 and MMP-8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL-6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates. CONCLUSION: ECM (lumican, SPRAC, TGFBI, and TGF-ß1)- and serine protease (uPA)-associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL-8, MMP-8, and IL-6)-associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.

Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.

To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. When evaluating systematic variation in these markers over time, we found that multiple biomarkers consistently varied across participants' two pre-infection or two post-ART-suppression specimens. Additionally, we compared changes in biomarkers after vs before HIV acquisition. Across 47 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decrease in LBP. Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to delaying ART for ~24 weeks after HIV diagnosis. These findings provide insight into potential mediators by which immediate-ART initiation improves health outcomes, perhaps because immediate-ART limits the size of the HIV reservoir or limits immune dysregulation that in turn trigger systemic inflammation.

Multiplex Assay to Determine Acute Phase Proteins in Modified Live PRRSV Vaccinated Pigs.

Acute phase protein (APP) response to vaccine challenges is an attractive alternative to natural infection for identifying pigs with increased disease resilience and monitoring the productive performance. Currently, the methods used for APP quantification are diverse and often based on techniques that use antibodies that are not necessarily pig specific. The objective of this work is the development of a method based on a UPLC-SRM/MS system for simultaneous determination of haptoglobin, apolipoprotein A1, C-reactive protein, pig-major acute protein, and serum amyloid A and its application in pigs to monitor the effect of a vaccine administered against porcine reproductive and respiratory syndrome virus (PRRSV). With the aim of tracing the complete analytical process for each proteotypic peptide, a synthetic QconCat polypeptide construct was designed. It was possible to develop an SRM method including haptoglobin, apolipoprotein A1, pig-MAP, and serum amyloid A1. The PRRSV vaccine only affected haptoglobin. The pigs with positive viremia tended to show higher values than negative pigs, reaching significant differences in the three haptoglobin SRM-detected peptides but not with the data acquired by immunoenzymatic and spectrophotometric assays. These results open the door to the use of SRM to accurately monitor APP changes in experimental pigs.

Lipopolysaccharide-binding protein in Crohn's disease patients: a promising noninvasive biomarker monitoring disease activity.

BACKGROUND: Following STRIDE-II recommendations, the discovery of novel noninvasive biomarkers, beyond the use of C-reactive protein (CRP) and fecal calprotectin, remains a medical need to further improve the monitoring of patients with inflammatory bowel disease (IBD). This study aims to evaluate the potential of serum lipopolysaccharide-binding protein (LBP) in monitoring IBD activity. METHODS: This retrospective cross-sectional study included 69 IBD patients (43 Crohn's disease and 26 ulcerative colitis) and 82 controls. Serum LBP levels were measured by ELISA. Clinical, biological and endoscopic parameters were analyzed for IBD patients with no reports of missing data. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP. RESULTS: IBD patients displayed a significantly higher LBP median [29.6 µg/ml (19.8-38.8) in Crohn's disease and 22.8 (13.7-38.8) in ulcerative colitis] than controls [5.8 (4.7-7.3), P  < 0.001] with little overlapping distributions. In Crohn's disease patients, LBP levels gradually increased with endoscopic activity scores demonstrating a 1.7-fold rise in active patients compared to remitter patients ( P  = 0.02). LBP level exhibited a positive correlation with CRP ( ρ  = 0.75, P  < 0.001) as well as fecal calprotectin ( ρ  = 0.42, P  < 0.01), both of which further increased when excluding cases that did not match endoscopic activity. CONCLUSION: LBP might be a promising noninvasive biomarker for monitoring disease activity, especially in Crohn's disease patients. In clinical situations where current biomarkers lack sensitivity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions.

Assessment of cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin to distinguish acute kidney injury from other diseases in dogs.

BACKGROUND: Cell cycle arrest biomarkers (tissue inhibitor of metalloproteinase-2 [uTIMP-2] and insulin-like growth factor binding protein 7 [uIGFBP7]), and neutrophil gelatinase-associated lipocalin (NGAL) variables are valuable biomarkers for early diagnosis of acute kidney injury (AKI) in people. OBJECTIVES: To evaluate uTIMP-2, uIGFBP7, fractional excretion of NGAL (FeNGAL), and urinary to serum NGAL ratio (u/sNGAL) in healthy dogs, dogs with AKI, dogs with chronic kidney disease (CKD), and critically ill (CI) dogs. ANIMALS: Forty-two client-owned dogs (healthy, n = 10; AKI, n = 11; CKD, n = 11; CI, n = 10). METHODS: Prospective, observational study. After assessment of routine renal biomarkers, stress (uTIMP-2, uIGFBP7) and damage (NGAL) biomarkers were measured, using ELISA kits, and normalized to urinary creatinine (uCr). RESULTS: Normalized uTIMP-2 and [uTIMP-2] × [uIGFBP7]/uCr were significantly higher in the AKI group (median 151.9 [range, 2.2-534.2] and 62.9 [1.1-266.8] pg/mL respectively), compared to healthy dogs (0.3 [0.2-74.7]; P < .001 and 0.16 [0.1-58.1] pg/mL; P < .001), dogs with CKD (0.7 [0.3-742.5]; P = .04 and 0.37 [0.2-180.1] pg/mL; P = .03) and CI dogs (1.9 [0.2-37.0]; P = .03 and 0.8 [0.1-16.1] pg/mL; P = .02). Fractional excretion of NGAL was significantly higher in dogs with AKI (54.17 [7.93-155.32] %), than in healthy (0.03 [0.01-0.21] %; P < .001) and CI dogs (3.05 [0.05-28.86] %; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Normalized uTIMP-2, [uTIMP-2] × [uIGFBP7]/uCr, and FeNGAL can be valuable renal biomarkers for early diagnosis of AKI in dogs.

Plasma concentration of serum amyloid A and lipopolysaccharide binding protein in horses with laminitis resulted from hindgut acidosis.

Many studies have shown a strong correlation between Hindgut Acidosis (HGA) and the occurrence of laminitis in horses; therefore, the early diagnosis of HGA is essential. In this study, we investigated changes in the plasma concentrations of lipopolysaccharide-binding protein (LBP) and serum amyloid A (SAA) as inflammatory markers in horses with laminitis. Sixteen healthy male Arabian horses that had cecal cannulation without visible laminitis or general symptoms were randomly divided into two groups. The horses were fed two different diets in a forage-to-concentrate ratio. Blood samples were collected on Days 1, 10, and 20. The primary objective of this study was to analyze plasma levels of LBP and SAA. Cecal specimens were obtained from each equine subject on three designated days: days 1, 10, and 20. The second objective was to assess the levels of pH and volatile fatty acids (VFA) in the samples. Throughout the study period, horses fed a high-concentrate diet exhibited a significantly elevated average lameness grade on days 10 and 20 compared to the initial stage (P < 0.001). On day 20, a significant increase in the concentration of SAA was observed in horses fed a high-concentrate diet, in contrast to the initial stage of the study. LBP levels in the plasma were significantly elevated on days 10 and 20 in horses fed a high-concentrate diet. Based on our findings, it is recommended that the evaluation of plasma LBP concentrations is more effective than SAA for the early identification of HGA in horses fed a high-grain diet.

Serum bile acids profiles are altered without change of the gut microbiota composition following a seven-day prednisolone therapy in severe alcoholic hepatitis.

Severe Alcoholic Hepatitis (sAH) is an acute form of liver injury caused by chronic and heavy alcohol drinking. A one-month corticosteroids course is the only sAH reference treatment, and its interactions with the Gut Microbiota (GM), which is a key contributor to liver injury, remain unknown. To evaluate the evolution of the GM in sAH patients, we retrospectively investigated the composition of the GM of 27 sAH patients at the Amiens University Hospital before (D0) and after (D7) a 7-day corticotherapy course using fecal metagenomics sequencing. We also quantified fecal Short-Chain Fatty Acids (SCFA) and fecal and serum Bile Acids (BA), as well as serum Lipopolysaccharide-Binding Protein (LBP). Overall, the community and taxonomical analyses did not reveal any GM evolution between D0 and D7, nor did the SCFA profiles analysis. However, in serum but not fecal samples, the ratio of glyco-conjugated to tauro-conjugated BA was significantly reduced at D7, independently of the response to treatment, while two BA were enriched in non-responder patients. LBP concentration significantly diminished between D0 and D7, which may indicate an improvement of the gut barrier. The stability of the GM of sAH is interesting in the perspective of new treatments based on GM modulation.

There is a gap in the understanding of the effects of corticosteroids on the gut microbiota of severe alcoholic hepatitis patients.In this study, the composition of the Gut Microbiota of sAH patients treated with prednisolone remains unchanged after 7 days of prednisolone treatment.Short-Chain Fatty Acid profiles are not impacted by the treatment, while Bile Acids profiles change in serum but not in stool samples.Responders and non-responders show different lipopolysaccharide-binding protein serum concentration evolution across time, as well as distinct Bile Acid profiles.

Identification of novel biomarkers of acute phase response in chickens challenged with Escherichia coli lipopolysaccharide endotoxin.

BACKGROUND: The chicken's inflammatory response is an essential part of the bird's response to infection. A single dose of Escherichia coli (E. coli) lipopolysaccharide (LPS) endotoxin can activate the acute phase response (APR) and lead to the production of acute phase proteins (APPs). In this study, the responses of established chicken APPs, Serum amyloid A (SAA) and Alpha-1-acid-glycoprotein (AGP), were compared to two novel APPs, Hemopexin (Hpx) and Extracellular fatty acid binding protein (Ex-FABP), in 15-day old broilers over a time course of 48 h post E.coli LPS challenge. We aimed to investigate and validate their role as biomarkers of an APR. Novel plant extracts, Citrus (CTS) and cucumber (CMB), were used as dietary supplements to investigate their ability to reduce the inflammatory response initiated by the endotoxin. RESULTS: A significant increase of established (SAA, AGP) and novel (Ex-FABP, Hpx) APPs was detected post E.coli LPS challenge. Extracellular fatty acid binding protein (Ex-FABP) showed a similar early response to SAA post LPS challenge by increasing ~ 20-fold at 12 h post challenge (P < 0.001). Hemopexin (Hpx) showed a later response by increasing ∼5-fold at 24 h post challenge (P < 0.001) with a similar trend to AGP. No differences in APP responses were identified between diets (CTS and CMB) using any of the established or novel biomarkers. CONCLUSIONS: Hpx and Ex-FABP were confirmed as potential biomarkers of APR in broilers when using an E. coli LPS model along with SAA and AGP. However, no clear advantage for using either of dietary supplements to modulate the APR was identified at the dosage used.