Negative Acute Phase Proteins Research Articles

Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant.

Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.

PSVI-25 A Phytogenic Additive Improves Immune Responses of Growing Beef Cattle on Grazing System

Abstract Our objective was to evaluate the effect of a phytogenic additive in protein supplement for grazing Nellore young bulls on serum protein profile. One hundred and fourteen animals (iBW, n = 114; 273 ± 4.46 kg) were allocated for 152 days in six pastures of Brachiaria brizantha cv. Marandu (̴7 ha each), and randomly distributed in six treatments with or without additives on protein supplement (30% crude protein). Treatments were: 1) Negative Control (CON), with no additive; 2) Positive Control, with 15 ppm of Monensin (MON); 3) Digestarom (DSM Nutritional Products) at 0.2 g· animal-1· /day-1 (D0.2); 4) Digestarom at 0.4 g· animal-1· /day-1 (D0.4); 5) Digestarom at 0.6 g· animal-1· /day-1 (D0.6) and 6) Digestarom at 0.8 g· animal-1· /day-1 (D0.8). Supplement was offered ad libitum. Additives dosages were adjusted weekly to achieve the targeted dose/animal. Blood samples were collected in the last day and analyzed for positive acute phase proteins (increases with the inflammation response), haptoglobin (HAP) and glycoprotein (GLY); negative acute phase protein (decreases with the inflammation), transferrin (TRA); and Immunoglobulins A and G. Data were analyzed using SAS PROC GLIMMIX. Significance of 5% was adopted. Contrasts of use of Monensin, use of Digestarom, type of additive, and linear and quadratic effects of Digestarom were evaluated. Compared with MON, Digestarom decreased (P < 0.05) HAP (124 vs. 76.2 mg/dL) and GLY (1,361 vs. 85.6 mg/dL). TRA increased (P < 0.05) with Digestarom (310 and 307 mg/dL for D0.6 and D0.8, vs. 204 and 177 mg/dL for CON and MON). Digestarom increased (P < 0.05) immunoglobulins A (193, 218 and 225 mg/dL for D0.4, D0.6 and D0.8) and G (1.5 g/dL for D0.4, D0.6 and D0.8) compared with CON (IgA 146 mg/dL and IgG 0.9 g/dL) and MON (IgA 93 mg/dL and IgG 0.3 g/dL). Digestarom levels also showed a quadratic effect on TRA (including 165 and 245 mg/dL for D0.2 and D0.4) and on IgA and IgG (including 124 mg/dL and 0.8 g/dL for D0.2). Overall serum protein responses of the animals receiving Digestarom (reduced haptoglobin and glycoprotein, and graeter transferrin, IgA and IgG) demonstrates that these animals had improved immune responses and could be better able to respond to infectious and stress challenges.

Knockdown of coagulation factor VII has potential anticoagulant and anti-inflammatory effects in a mouse model of group A streptococcal sepsis

Infections originating from subcutaneous tissues are among the most common invasive infections caused by group A streptococcus (GAS) and associated with systemic coagulation activation. The role of intrinsic coagulation factors on GAS virulence has recently been determined, but the role of the extrinsic coagulation factor VII is unknown. Using a mouse model, in which GAS-sepsis emerges from a subcutaneous infection, we show that FVII is a negative acute phase protein. F7 knockdown using antisense oligonucleotides resulted in an attenuated systemic coagulation activation and inflammatory response in septic animals. The findings indicate FVII's ability to modify the host response.

Apolipoprotein A1 and serum amyloid A in dogs with sepsis and septic shock.

Apolipoprotein-A1 (Apo-A1) acts as a negative acute phase protein (APP) during inflammatory states, and has a potential prognostic value in people and dogs with sepsis. The aim of this retrospective study was to investigate the association of serum Apo-A1 concentration with disease severity, multiorgan dysfunction syndrome (MODS) and outcome in a population of dogs with sepsis, and to assess its correlation with major canine APPs. Ninety-nine dogs with uncomplicated sepsis (n = 78) or septic shock (n = 21) were included. The serum concentration of Apo-A1, C-reactive protein (CRP) and serum amyloid A (SAA) were recorded, alongside the canine acute patient physiologic and laboratory evaluation fast (APPLEfast) score and the presence of MODS. Dogs with septic shock had significantly lower serum Apo-A1 concentrations (106.3 ± 22.7 mg/dl; reference interval: 123.0-142.3 mg/dl), higher APPLEfast score (30, 13-38) and greater frequency of MODS (67%) compared to those with uncomplicated sepsis (117.9 ± 19.3 mg/dl; 25, 6-33 and 8%, respectively) (P = 0.0201; P = 0.0005; P < 0.0001, respectively). Similarly, dogs with MODS had significantly lower serum Apo-A1 concentrations (104.1 ± 4.6 mg/dl) and higher APPLEfast score values (31, 13-38) compared to those without MODS (118.32 ± 2.1 mg/dl and 26, 6-33, respectively) (P = 0.0050 and P = 0.0038, respectively). Conversely, neither CRP nor SAA were different between these groups. No difference in serum APPs concentrations was detected between survivors and non-survivors. Significant negative correlations were detected between serum Apo-A1 and SAA (P = 0.0056, r = -0.277), and between serum Apo-A1 and the APPLEfast score (P = 0.0027, r = -0.3). In this population, higher values of the APPLEfast score and the presence of MODS were independently associated with a higher risk of death. Our study shows that Apo-A1 is a useful biomarker of sepsis severity in dogs, since it is decreased in those with septic shock and MODS. Further prospective investigations are deemed to evaluate the applicability of Apo-A1 to predict sepsis course and response to treatment in septic dogs.

Acute phase proteins levels in horses, after a single carbohydrate overload, associated with cecal alkalinization.

Horses submitted to carbohydrate overload can develop laminitis due to changes in cecal pH and microbiota, followed by an increase in transmural absorption of luminal content, including bacterial toxins. In response to acute injury there is hepatic overproduction of several proteins known as acute phase proteins (APP). Few studies have evaluated protein fractionation to characterize the inflammatory response in acute laminitis. The aim of this study was to test the viability of an experimental model to induce acute laminitis, using a single carbohydrate overload, and the influence of a buffering solution on the development of the disease; also, study the kinetics of APP during acute laminitis, as well as the correlation between these proteins and clinical signs associated to this syndrome. Ten healthy horses were divided in a factorial and randomized way into four groups (n = 5): control group (CG), starch group (SG), buffer group (BG), and starch C buffer group (SBG). They were evaluated at seven times (T0h, T4h, T8h, T12h, T24h, T48h, and T72h), which included clinical evaluation and blood sample collection. Total serum protein and albumin concentrations were determined by colorimetry and the other APP by polyacrylamide gel electrophoresis containing sodium dodecyl sulfate and commercial ELISA kits. Data were analyzed by two-way ANOVA, followed by Tukey's test (p < 0.05). The correlation between clinical signs and APP were verified using the Pearson's correlation coefficient. 40% of the animals from SG and 60% from SBG developed clinical laminitis. A single administration of buffer solution was not able to prevent clinical signs of laminitis. There was no difference between groups on total serum protein, albumin, serum amyloid A and C-reactive protein concentrations (p > 0.05). Transferrin, considered a negative APP, showed a positive response pattern in SG and SBG. Ceruloplasmin had a positive correlation with Obel grade, heart rate on animals from SGB and number of steps on horses submitted to starch overload (SG and SBG). Ceruloplasmin, α-1-antitrypsin and haptoglobin concentrations increased in SBG, suggesting an inflammatory response in animals of this group. Changes in clinical parameters were also more evident in the SBG, corroborating the protein fractionation findings.

Ganoderma lucidum as Anti-Inflammatory Agent on The Level of Albumin and Globulin in Rat (Rattus Norvegicus) Rheumatoid Arthritis (RA) Model

Abstrak: Inflammation is one of the immune system's responses to infection, irritation, also cell damage. Inflammation stimulates pro-inflammatory biomarkers. Albumin and globulin are included as inflammatory biomarkers, albumin is a negative acute phase protein (-APP), which will decrease, and globulin is a positive acute phase protein (+APP), which will increase due to inflammation. Ganoderma lucidum is a medicinal mushroom with anti-inflammatory potential that could increase the albumin level in blood due to inflammation. This research aimed to examine the effect of G. lucidum extract on the albumin and globulin level of inflamed white rats anddetermine the most effective dose of extract to be an anti-inflammatory agent. The study was conducted with a completely randomized design (CRD) consisting of 6 treatments of healthy control (HC), inflamed rats as negative control (C-), inflamed rats with Na-diclofenac administration (C+), and inflamed rats with G. lucidum extract administration with a dose of 250, 500, 750 mg/kg BW (T1, T2, and T3) with four replications each. The independent variable is the dose variant of G. lucidum (250, 500, 750 mg/kg BW), with the dependent variable being the changesin albumin and globulin levels. The main parameters are albumin and globulin levels, and the support parameter is the GC-MS test. The data were processed using Analysis of Variance (ANOVA) at an error rate of 5%, followed by Duncan's analysis at 95% confidence level. The results show that mushroom G. lucidum extract administration with a dose of 250 mg/kg BW is the most effective dose to be ana dose of 250 mg/kg BW, which is the most effective anti-inflammatory agent.

Assessment of C-Reactive Protein/Serum Albumin Ratio in Relation to Acute Presentation and Early Outcome of Patients with Acute Coronary Syndrome

Background: Acute coronary syndrome (ACS) is the leading cardiovascular (CV) cause of mortality. C reactive protein (CRP) has linked with long-term risk of recurrent cardiovascular events or death. Albumin, in contrast to CRP known as a negative acute-phase protein. Thus a newly introduced marker assessed relation of CRP to albumin ratio (CAR), which may provide better results than the use of either marker alone. The aim of the study is to assess the association of C-reactive protein to albumin ratio (CAR) with in-hospital short-term major adverse cardiac events (MACEs) in acute coronary syndrome (ACS) patients. Patients & Methods: A multi-centers prospective cohort study was conducted at coronary intensive care units (CICU) in Baghdad during the period from March to October 2021 that included a total of 132 patients who were diagnosed as a case of ACS. They were assessed for major adverse cardiac events (MACEs) like cardiogenic shock, arrhythmias, post-MI angina, and acute heart failure while inside the ward, in addition to need for early interventional therapeutic approach in relation to (CAR) immediately at time of admission to hospital. Results: High values of CAR, whether using hs-CRP or CRP, were identified as an independent predictor for in-hospital MACEs (P value < 0.001 and 0.002 respectively. A cut-off value of CAR (using hs-CRP) is 3.18 mg/L in context of discrimination between medically treated ACS patients and death outcome in term of high CAR. A cut-off value of CAR (using CRP) as 9.13 mg/L suggests the usefulness in discrimination of outcome in relation to medically managed patients, at presentation. CAR had a positive significant correlation with hospital stay (r = 0.210, P = 0.036). Conclusion: The CAR was independently correlated with in-hospital short-term MACEs and can be used for risk stratification in patients with ACS.

Post-translational modifications glycosylation and phosphorylation of the major hepatic plasma protein fetuin-A are associated with CNS inflammation in children.

Fetuin-A is a liver derived plasma protein showing highest serum concentrations in utero, preterm infants, and neonates. Fetuin-A is also present in cerebrospinal fluid (CSF). The origin of CSF fetuin-A, blood-derived via the blood-CSF barrier or synthesized intrathecally, is presently unclear. Fetuin-A prevents ectopic calcification by stabilizing calcium and phosphate as colloidal calciprotein particles mediating their transport and clearance. Thus, fetuin-A plays a suppressive role in inflammation. Fetuin-A is a negative acute-phase protein under investigation as a biomarker for multiple sclerosis (MS). Here we studied the association of pediatric inflammatory CNS diseases with fetuin-A glycosylation and phosphorylation. Paired blood and CSF samples from 66 children were included in the study. Concentration measurements were performed using a commercial human fetuin-A/AHSG ELISA. Of 60 pairs, 23 pairs were analyzed by SDS-PAGE following glycosidase digestion with PNGase-F and Sialidase-AU. Phosphorylation was analyzed in 43 pairs by Phos-TagTM acrylamide electrophoresis following alkaline phosphatase digestion. Mean serum and CSF fetuin-A levels were 0.30 ± 0.06 mg/ml and 0.644 ± 0.55 μg/ml, respectively. This study showed that serum fetuin-A levels decreased in inflammation corroborating its role as a negative acute-phase protein. Blood-CSF barrier disruption was associated with elevated fetuin-A in CSF. A strong positive correlation was found between the CSF fetuin-A/serum fetuin-A quotient and the CSF albumin/serum albumin quotient, suggesting predominantly transport across the blood-CSF barrier rather than intrathecal fetuin-A synthesis. Sialidase digestion showed increased asialofetuin-A levels in serum and CSF samples from children with neuroinflammatory diseases. Desialylation enhanced hepatic fetuin-A clearance via the asialoglycoprotein receptor thus rapidly reducing serum levels during inflammation. Phosphorylation of fetuin-A was more abundant in serum samples than in CSF, suggesting that phosphorylation may regulate fetuin-A influx into the CNS. These results may help establish Fetuin-A as a potential biomarker for neuroinflammatory diseases.

The human host response to monkeypox infection: a proteomic case series study.

The rapid rise of monkeypox (MPX) cases outside previously endemic areas prompts for a better understanding of the disease. We studied the plasma proteome of a group of MPX patients with a similar infection history and clinical manifestation typical for the current outbreak. We report that MPX in this case series is associated with a strong plasma proteomic response among nutritional and acute phase response proteins. Moreover, we report a correlation between plasma proteins and disease severity. Contrasting the MPX host response with that of COVID-19, we find a range of similarities, but also important differences. For instance, CFHR1 is induced in COVID-19, but suppressed in MPX, reflecting the different roles of the complement system in the two infectious diseases. Of note, the spatial overlap in response proteins suggested that a COVID-19 biomarker panel assay could be repurposed for MPX. Applying a targeted protein panel assay provided encouraging results and distinguished MPX cases from healthy controls. Hence, our results provide a first proteomic characterization of the MPX human host response and encourage further research on protein-panel assays in emerging infectious diseases.

Inflammation and Loss of Skeletal Muscle Mass in Chronic Limb Threatening Ischemia

Lower extremity peripheral arterial disease (PAD) is an atherosclerotic disease of the lower extremities. Atherosclerosis, inflammation, and sarcopenia are independently associated and potentiate each other. Inflammation is deeply involved in the formation and progression of atherosclerosis and is also involved in the pathophysiology of sarcopenia. Sarcopenia is defined as low muscle mass, with low muscle strength. This study aims to determine the differences in skeletal muscle characteristics and in inflammatory parameters between patients with claudication and with chronic limb threatening ischemia (CLTI). An observational, prospective study in patients with PAD was conducted from January 2018 to December 2020. The clinical characteristics and the cardiovascular risk factors were prospectively registered. The inflammatory parameters determined were: positive acute phase proteins (C-reactive Protein- CRP- and fibrinogen) and negative acute phase proteins albumin, total cholesterol and high-density lipoprotein (HDL). The skeletal muscle area and density were quantified with a computed topography (CT) scan. The strength was determined with a Jamar® hydraulic hand dynamometer. A total of 116 patients (mean age: 67.65±9.53 years-old) 64% with claudication and 46% with CLTI were enrolled in the study. No differences were registered between patients with claudication and CLTI on age, cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, and smoking habits) and medication. There was a higher prevalence of men in the claudication group (88.89% vs. 71.70%, P=0.019). Analyzing the inflammatory parameters, we noted that patients with CLTI had increased serum levels of positive acute phase proteins: CRP (37.53±46.61mg/L vs. 9.18±26.12mg/L, P=0.000), and fibrinogen (466.18±208.07mg/dL vs. 317.37±79.42mg/dL, P=0.000). CLTI patients had decreased negative acute phase proteins: albumin (3.53±0.85g/dL vs. 3.91±0.72g/dL, P=0.001), total cholesterol (145.41±38.59mg/dL vs. 161.84±34.94mg/dL, P=0.013) and HDL (38.70±12.19mg/dL vs. 51.31±15.85mg/dL, P=0.000). We noted that patients with CLTIhad lower skeletal muscle area and mass (14,349.77±3,036.60mm2 vs. 15,690.56±3,183.97mm2P=0.013; 10.11±17.03HU vs. 18.02±13.63HU P=0.013). After adjusting for the variable sex, the association between skeletal muscle density and CLTI persisted (r (97)=-0.232, P=0.021). The groups did not differ in strength (patients with claudication: 25.39±8.23 Kgf vs. CLTI: 25.17±11.95 Kgf P=0.910). CLTI patients have decreased skeletal muscle mass and a systemic inflammation status. Recognizing the deleterious triad of atherosclerosis, inflammation and loss of skeletal mass patients with CLTI is an opportunity to improve medical therapy and to perform a timely intervention to stop this vicious cycle.

Evaluation of acute phase proteins, adiponectin and endothelin-1 to determine vascular damage in dogs with heartworm disease (Dirofilaria immitis), before and after adulticide treatment

Previous studies have shown the existence of an acute phase response in dogs with heartworm (Dirofilaria immitis), probably caused by the vascular inflammation that occurs during the pathogenesis of this disease. In addition, it has been seen that this acute phase response persists after finishing treatment, especially in dogs with pulmonary hypertension (PH). Furthermore, echocardiographic studies have shown that PH and endarteritis appear to persist for at least 10 months after completion of adulticide treatment, suggesting that the vascular changes in these dogs may not be reversible. Therefore, the objective of this study was to evaluate the serum concentrations of different positive acute phase proteins (APP) [C reactive-protein (CRP), haptoglobin and ferritin] and negative APP (albumin and paraoxonase-1 (PON-1)), and the usefulness of the endothelin-1 (ET-1) and adiponectin, in dogs infected by D. immitis to evaluate their usefulness as diagnostic biomarkers of vascular damage and PH and their progression throughout therapy up to 7 months after the end of adulticide treatment. Twenty-five heartworm-infected dogs received adulticide treatment, and serum measurements were performed on the day of diagnosis (day 0), day of discharge (day 90), and 6 months after discharge (day 270). In addition, presence or absence of PH was also echocardiographically determined using the Right Pulmonary Artery Distensibility Index. PH was present in 44% of the dogs on day 0 and day 90, and in 48% of dogs on day 270. Alterations were observed in the concentrations of all APP throughout the study, persisting the alterations in PON-1 and ferritin on day 270. Depending on the presence or absence of PH, CRP showed significant differences throughout the study, as did ET-1. On the other hand, adiponectin did not show variations throughout the study, so it did not seem a useful marker in this disease. These results could reflect the possible persistence of vascular inflammation up to 7 months after finishing treatment, whether or not there was PH, and consolidate the study of APP as useful markers in heartworm disease. Moreover, persistent PH could be the consequent clinical manifestation in dogs with more severe vascular alterations so the study of APP, especially CRP, and ET-1 could be especially advantageous in these patients in the early evaluation of the disease, as well as for the determination of disease severity, monitoring therapeutic responses, and predicting outcomes.

Peri-Operative Fall in Serum Albumin Levels Correlate Well With Outcomes in Children Undergoing Emergency Abdominal Surgery: A Prospective Study From a Resource-Limited Setting.

BackgroundAlbumin is a negative acute-phase protein as its levels fall after injury, sepsis, and surgical stress. A review of the literature suggests that serum albumin level drops rapidly after surgery in adults and correlates well with the outcomes. However, there is limited data on the use of peri-operative fall in serum albumin levels as an outcome predictor in children undergoing emergency abdominal surgeries. We aim to investigate the correlation between the degree of peri-operative fall in serum albumin levels and the outcomes in children undergoing emergent abdominal surgeries.Materials and methodsThis prospective study included all children aged 2-15 years undergoing emergent abdominal surgeries between January 2019 to June 2020 at our center. Preoperative serum albumin level (A1) was recorded for all children. Postoperative day 0 serum albumin level (A2) was sent 4-6 hours following the surgery. The degree of peri-operative fall in serum albumin level (∆A) was calculated by subtracting A2 from A1. Patients were then grouped on the basis of ∆ A, i.e. groups 1 and 2 with ∆ A < 0.5 and ≥ 0.5 gm/dl respectively. Additional data like diagnosis, surgical procedure, duration of surgery, complications, and length of hospital stay were also recorded. Recorded parameters in group 1 were then compared to group 2 statistically.ResultsFifty-six children (male to female ratio {M:F} = 1.5:1), who met the inclusion criteria during the study period, were included in the study. Groups 1 and 2 comprised 38 and 18 children respectively. The postoperative serum albumin levels were significantly lower in group 2 (p = 0.0005). Duration of surgery was significantly higher in group 2 (p = 0.0474). Complications and length of hospital stay were significantly higher in group 2 (p = 0.0107 and p = 0.0375 respectively).ConclusionThe present study evaluated the fall in peri-operative serum albumin level (∆A) in children undergoing emergent abdominal surgery as a marker of stress. Higher values of ∆A (≥ 0.5 gm/dl) depicted a significant correlation with complications requiring re-laparotomy and a longer length of hospital stay.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

Serum kallistatin as a marker of severity of liver fibrosis in cirrhosis: A cross-sectional observational study.

ABSTRACTBackground:Liver cirrhosis is among the leading causes of morbidity and mortality worldwide. Although liver biopsy is the gold standard for the assessment of liver fibrosis in cirrhosis, it has its own limitations. Therefore, noninvasive methods to detect liver fibrosis are widely preferred. However, they also have their own limitations. Thus, there is always a need to extend the battery of serum-based assays. Kallistatin is a protein synthesized primarily in the liver. As it is a negative acute-phase protein, its blood level decreases with a decline in liver function. In our study, we explored the relationship between serum kallistatin and radiological evidence of liver fibrosis by transient elastography to determine if kallistatin levels can be used as a diagnostic marker of liver fibrosis.Materials and Methods:A cross-sectional study of 1-year duration was conducted at a leading tertiary care hospital in northern India. Patients between 15 and 75 years of age having evidence of chronic liver disease were enrolled. All enrolled patients were evaluated by detailed history, physical examination, and relevant investigations. Serum kallistatin levels were quantified using the ELISA method. Grading of liver fibrosis was done using transient elastography. A FibroScan scoring card was used to convert FibroScan results measured in kPa into the Metavir scale F1–F4Results:A total of 128 subjects, including 64 patients with cirrhosis and 64 healthy controls, were enrolled. Our study suggested that FibroScan values were significantly higher in cases as compared to controls. The kallistatin level of cases was significantly lower than that of controls. An inverse correlation was found between FibroScan value and kallistatin level among casesConclusion:We conclude that serum kallistatin levels are low in patients with liver fibrosis and can be used as a potential marker of liver fibrosis.

Changes in serum PON1 activity, gene expression and their association with lipid profile parameters in healthy Darehshori neonatal foals: a preliminary study

Paraoxonase 1 (PON1) contributes to the antioxidant mechanisms that prevent lipoprotein oxidation and act as a negative acute-phase protein. This study aimed to evaluate changes in serum PON1 activity, the leukocyte PON1 gene expression, as well as lipid profile tests (LDL, HDL, triglyceride, and cholesterol) in 16 healthy Darehshori newborn foals up to 60 days of life. Blood samples were collected at 1, 7, 15, 30, and 60 days used for detecting biochemical parameters, PON1 activity, and, and its gene expression, using realtime RT-PCR. Low levels of PON1 activity were observed at birth, which increased significantly with increasing age at days 7, 15, 30, and 60. In addition, HDL levels were significantly increased at 15, 30, and 60 days in male foals, and in contrast, LDL and cholesterol levels were significantly reduced on days 15, 30, and 60 compared to the first day of life in newborn foals. For the first time, PON1 mRNA was detected in foal leukocytes and its gene expression showed a significant decrease compared to the birthday. The positive correlations between PON1 expression/HDL, LDL, and cholesterol in the first week of life and between PON1 enzyme activity/ HDL, LDL, and cholesterol in different samples and sexes may indicate an adaptive increase in antioxidant defenses in response to oxidative stress. The authors suggest that PON1 expression in leukocytes may be related to the enzyme?s ability to reduce intracellular oxidant levels.

Measurement of paraoxonase and telomerase enzymes and HDL (high density lipoprotein) values and research of their possible relationships with each other in bloodserum of obese cats

Today, obesity is seen as a serious health problem in domestic cats. Paraoxonase1 (PON1) is a negative acute phase protein with anti-inflammatory properties. PON1 is transported by linking to different parts of HDL in the blood and has a protective feature of HDL against oxidation. Telomerase is reverse transcriptase enzyme that synthesizes and protects telomeres. Telomere length becomes shorter due to stress, obesity, and lack of exercise. In this study, paraoxonase1, telomerase enzymes and HDL values in blood serum of obese and non-obese cats were measured and their relationships with each other were evaluated. Body fat ratio in cats with body fat measurement system, those above 30% were evaluated as obese, and those below 30% were evaluated as the control group. Paraoxonase1 (p&amp;lt;0.001), telomerase (p&amp;lt;0.001) and HDL (p&amp;lt;0.008) values showed a statistically significant difference between the both groups, it was found to be lower in the obese group compared to the control group. As a result; paraoxonase1 and telomerase enzymes which are parameters of oxidative stress and are known to decrease in inflammation, were also found to be decreased in obese cats. The fact that HDL values are lower than the control group is an indicator that there are diseases that occur together with obesity.

Association of cardiometabolic microRNAs with COVID-19 severity and mortality.

AimsCoronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality.Methods and resultsWe performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality.ConclusionCirculating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response.

Albumin Infusion in Critically Ill COVID-19 Patients: Hemodilution and Anticoagulation.

Hypercoagulation is one of the major risk factors for ICU treatment, mechanical ventilation, and death in critically ill patients infected with SARS-CoV-2. At the same time, hypoalbuminemia is one risk factor in such patients, independent of age and comorbidities. Especially in patients with severe SARS-CoV-2-infection, albumin infusion may be essential to improve hemodynamics and to reduce the plasma level of the main marker of thromboembolism, namely, the D-dimer plasma level, as suggested by a recent report. Albumin is responsible for 80% of the oncotic pressure in the vessels. This is necessary to keep enough water within the systemic circulatory system and for the maintenance of sufficient blood pressure, as well as for sufficient blood supply for vital organs like the brain, lungs, heart, and kidney. The liver reacts to a decrease in oncotic pressure with an increase in albumin synthesis. This is normally possible through the use of amino acids from the proteins introduced with the nutrients reaching the portal blood. If these are not sufficiently provided with the diet, amino acids are delivered to the liver from muscular proteins by systemic circulation. The liver is also the source of coagulation proteins, such as fibrinogen, fibronectin, and most of the v WF VIII, which are physiological components of the extracellular matrix of the vessel wall. While albumin is the main negative acute-phase protein, fibrinogen, fibronectin, and v WF VIII are positive acute-phase proteins. Acute illnesses cause the activation of defense mechanisms (acute-phase reaction) that may lead to an increase of fibrinolysis and an increase of plasma level of fibrinogen breakdown products, mainly fibrin and D-dimer. The measurement of the plasma level of the D-dimer has been used as a marker for venous thromboembolism, where a fourfold increase of the D-dimer plasma level was used as a negative prognostic marker in critically ill SARS-CoV-2 hospitalized patients. Increased fibrinolysis can take place in ischemic peripheral sites, where the mentioned coagulation proteins can become part of the provisional clot (e.g., in the lungs). Although critically ill SARS-CoV-2-infected patients are considered septic shock patients, albumin infusions have not been considered for hemodynamic resuscitation and as anticoagulants. The role of coagulation factors as provisional components of the extracellular matrix in case of generalized peripheral ischemia due to hypoalbuminemia and hypovolemia is discussed in this review.

The C-reactive protein to prealbumin ratio on admission and its relationship with outcome in patients hospitalized for acute heart failure

BackgroundInflammation and malnutrition are common problems in patients who are hospitalized for acute heart failure (AHF). C-reactive protein (CRP) is an acute-phase reactant and nonspecific marker for evaluating systemic inflammation. There has been growing interest in prealbumin for nutritional assessment. Additionally, prealbumin is a negative acute-phase protein because its synthesis is suppressed in the inflammatory setting in which cytokines stimulate hepatic production of acute-phase proteins (e.g. CRP). Therefore, the CRP to prealbumin ratio (CP ratio) may be a comprehensive marker of inflammation and malnutrition. We evaluated the relationship of the CP ratio with mortality in patients with AHF. MethodsWe analyzed 257 hospitalized patients with AHF who had CRP and prealbumin levels examined on admission. ResultsThe median CP ratio on admission was 0.57, with an interquartile range of 0.11 to 1.94. In receiver operating characteristic curve analysis, the area under the curve was 0.729 and the optimal cut-off point of the CP ratio for all-cause death was >1.60 (sensitivity: 67.5%; specificity: 77.6%; p = 0.003). Kaplan-Meier survival curves showed that patients with a high CP ratio (>1.60) had a significantly greater risk of all-cause, cardiac, and non-cardiac death (log-rank test, all p<0.001) than patients with a low CP ratio (≤1.60). Multivariable analysis adjusted for imbalanced baseline variables showed that a high CP ratio was independently associated with higher all-cause mortality (adjusted hazard ratio 3.88; 95% confidence interval 1.91–7.86; p<0.001). ConclusionsThe ratio of two hepatic proteins, CRP and prealbumin, may be useful in risk stratification of patients with AHF.

Inflammatory diets are associated with lower total iron binding capacity in sera of young adults.

Chronic, systemic inflammation, which is associated with obesity and numerous other diseases, impairs iron status by increasing hepcidin concentration. Inflammation also decreases the concentration of transferrin, the main iron transport protein and a negative acute phase protein, which is indirectly assessed by measuring total iron binding capacity (TIBC). However, the contribution of diet-induced inflammation has not been studied. Data from two studies, namely Diet and Inflammation and Selenium and Inflammation Studies (total n=98) were used to assess the associations among Dietary Inflammatory Index (DII®) scores derived from three-day dietary records, body mass index (BMI=weight[kg]/height[m]2), inflammatory and hematological markers among young adults with normal-weight, overweight or obesity. Subjects' diets were also categorized as less inflammatory diets (LID) and inflammatory diets (ID) using cluster analysis. Independent t-test and regression analyses were used to assess associations in the data. Intakes of iron, proteins, fat, fiber, and calories were higher in the LID group compared to the ID group (p<0.05). Demographic characteristics and concentrations of C-reactive protein (CRP) and iron status biomarkers did not differ significantly between the two groups (p>0.05). Higher DII score was associated with increasing CRP (β+SE=0.23+0.07, p=0.002) and lower TIBC (β+SE=-8.46+3.44, p=0.02), independent of BMI category. The LID diet was associated with higher TIBC (β+SE=29.87+10.75, p=0.007) compared to the ID diet. In conclusion, inflammatory diets may impair iron status by reducing the iron binding capacity of transferrin.