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Alkaptonuria (AKU) is a rare autosomal recessive metabolic disorder caused by mutations in the homogentisate 1,2-dioxygenase (HGD) gene, leading to the accumulation of homogentisic acid (HGA), causing severe inflammatory conditions. Recently, the presence of serum amyloid A (SAA) has been reported in AKU tissues, classifying AKU as novel secondary amyloidosis; AA amyloidosis is characterized by the extracellular tissue deposition of fibrils composed of fragments of SAA. AA amyloidosis may complicate several chronic inflammatory conditions, like rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, chronic infections, neoplasms, etc. Treatments of AA amyloidosis relieve inflammatory disorders by reducing SAA concentrations; however, no definitive therapy is currently available. SAA regulation is a crucial step to improve AA secondary amyloidosis treatments. Here, applying a comprehensive in vitro and in silico approach, we provided evidence that HGA is a disruptor modulator of SAA, able to enhance its polymerization, fibril formation, and aggregation upon SAA/SAP colocalization. In silico studies deeply dissected the SAA misfolding molecular pathway and SAA/HGA binding, suggesting novel molecular insights about it. Our results could represent an important starting point for identifying novel therapeutic strategies in AKU and AA secondary amyloidosis-related diseases. [ABSTRACT FROM AUTHOR]

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the early diagnosis effect and clinical predictive value of serum amyloid A and C reactive protein in children with acute upper respiratory tract infection. A total of 324 children with acute upper respiratory tract infection (ARTI) who were treated in our hospital from October 2020 to April 2022 were selected as the research subjects. The variation of C-reactive protein concentration was tested by sphericity hypothesis, and the Greenhouse-Geisser method was used for in-depth analysis. The Receiver-Operating Characteristic (ROC) curve was drawn to evaluate the early predictive value of serum amyloid A and C reactive protein in children with acute upper respiratory tract. The concentrations of serum amyloid A and C reactive protein in children with ARTI changed significantly, with the increase of time, the concentration decreased, and the difference was statistically significant (P<0.05). The concentrations of amyloid A and C-reactive protein were significantly different, and the difference was statistically significant (P<0.05). Finally, the predictive effect of serum amyloid A and C reactive protein changes in children with ARTI was analyzed. From the ROC curve, it can be known that for both viral and bacterial upper respiratory tract infections, serum amyloid A and C reactive protein Proteins all have higher area under the line, and the ratio of the two is larger than the area under the line, both above 0.8. The serum amyloid A and C-reactive protein in the blood routine test of children with ARTI showed a changing trend. It was concluded that the changes of serum amyloid A and C-reactive protein can be used for early prediction of children with ARTI. It is of great value to improve the clinical treatment of ARTI. [ABSTRACT FROM AUTHOR]

Acute-phase serum amyloid A (SAA) can disrupt vascular homeostasis and is elevated in subjects with diabetes, cardiovascular disease, and rheumatoid arthritis. Cyclic nitroxides (e.g., Tempo) are a class of piperidines that inhibit oxidative stress and inflammation. This study examined whether 4-methoxy-Tempo (4-MetT) inhibits SAA-mediated vascular and renal dysfunction. Acetylcholine-mediated vascular relaxation and aortic guanosine-3′,5′-cyclic monophosphate (cGMP) levels both diminished in the presence of SAA. 4-MetT dose-dependently restored vascular function with corresponding increases in cGMP. Next, male ApoE-deficient mice were administered a vehicle (control, 100 µL PBS) or recombinant SAA (100 µL, 120 µg/mL) ± 4-MetT (at 15 mg/kg body weight via i.p. injection) with the nitroxide administered before (prophylaxis) or after (therapeutic) SAA. Kidney and hearts were harvested at 4 or 16 weeks post SAA administration. Renal inflammation increased 4 weeks after SAA treatment, as judged by the upregulation of IFN-γ and concomitant increases in iNOS, p38MAPK, and matrix metalloproteinase (MMP) activities and increased renal fibrosis (Picrosirius red staining) in the same kidneys. Aortic root lesions assessed at 16 weeks revealed that SAA enhanced lesion size (vs. control; p < 0.05), with plaque presenting with a diffuse fibrous cap (compared to the corresponding aortic root from control and 4-MetT groups). The extent of renal dysfunction and aortic lesion size was largely unchanged in 4-MetT-supplemented mice, although renal fibrosis diminished at 16 weeks, and aortic lesions presented with redistributed collagen networks. These outcomes indicate that SAA stimulates renal dysfunction through promoting the IFN-γ–iNOS–p38MAPK axis, manifesting as renal damage and enhanced atherosclerotic lesions, while supplementation with 4-MetT only affected some of these pathological changes. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to evaluate the combined diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in sepsis caused by urinary tract infection. Method: A total of 80 patients with urosepsis who were hospitalized were included in the study group, and 80 patients with urinary tract infection without sepsis were included in the control group. We collected the PCT, SAA, and CRP levels of patients following admission. Subsequently, we conducted a comparative analysis to assess the specificity, accuracy, and sensitivity of combined diagnostic approaches in contrast to individual diagnostic methods for blood PCT, SAA, and CRP. Results: The levels of PCT, SAA, and CRP in the study group were significantly higher than those in the control group, and the differences were statistically significant (P < 0.01). Multi-factor logistic regression analysis revealed that the levels of PCT (P = 0.003) and SAA (P = 0.014) were associated with urosepsis. The sensitivity of PCT was 87.133% and the specificity was 93.066%, which were higher than that of SAA and CRP. The specificity of the combined detection of the three was 95.670%, which was higher than that of PCT, SAA, and CRP alone. Correlation analysis revealed that PCT had a significant positive correlation with CRP and SAA (P < 0.01), and a weak correlation with white blood cell count (WBC) and fibrinogen (FIB) (P = 0.03 for WBC, P = 0.04 for FIB). Conclusion: PCT, SAA, and CRP indicators in patients with urosepsis are significantly elevated, and all three are valuable in the diagnosis of urosepsis. PCT alone has good diagnostic efficiency for urosepsis, and a certain correlation with other inflammatory factors. The diagnostic efficacy of the three indicators in combination is better than that of any one of the three, and is worthy of widespread clinical application. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for Ddimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE. [ABSTRACT FROM AUTHOR]

Introduction: The glutaraldehyde test (GAT) allows for animal-side semiquantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations. Methods: For the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and noninflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations. Results: Shortened GAT coagulation times were more closely correlated to serum globulin (rs = -0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs = -0.64) and the Clauss method (rs = -0.70). Cows with a markedly (=3 min) or moderately (4-6 min) shortened coagulation time had higher (p < 0.001) plasma haptoglobin and SAA concentrations than cows with a negative test result. Total leukocyte, monocyte and neutrophil concentrations did not differ significantly between groups. An identified cut-off for the GAT coagulation time of =14 min had a sensitivity and specificity of 54.4 and 100%, respectively, for the prediction of an inflammatory state based on clinical findings and/or increased plasma haptoglobin or SAA concentrations. Discussion: In conclusion, this study demonstrates considerable diagnostic agreement between positive GAT results and increased plasma concentrations of haptoglobin and SAA. Despite high specificity, the test lacks sensitivity in case of acute inflammatory conditions indicating that plasma acute phase protein concentrations and hematologic findings can provide additional diagnostic information if the GAT is negative. [ABSTRACT FROM AUTHOR]

Purpose of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis. Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases. Histopathological examination is the gold standard of diagnosis, but magnetic resonance imaging can be used to detect cardiac involvement. There is yet no treatment option for the clearance of amyloid fibril deposits; therefore, the management strategy primarily aims to reduce serum amyloid A protein. Anti-inflammatory biologic agents have drastically expanded our therapeutic armamentarium. Kidney transplantation is preferred in patients with kidney failure, and the recurrence of amyloidosis in the allograft has become rare as transplant recipients have started to benefit from the new agents. Summary: The management of AA amyloidosis has been considerably changed over the recent years due to the novel therapeutic options aiming to control inflammatory activity. New agents capable of clearing amyloid deposits from the tissues are still needed. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is a cardiovascular risk factor and may serve as a predictor of infarct-related artery (IRA) patency in patients with ST-segment elevation myocardial infarction (STEMI). We measured SAA levels in STEMI patients who underwent percutaneous coronary intervention (PCI) and investigated their association with IRA patency. According to the Thrombolysis in Myocardial Infarction (TIMI) flow grade, 363 STEMI patients undergoing PCI in our hospital were divided into an occlusion group (TIMI 0-2) and a patency group (TIMI 3). The SAA level before PCI was significantly higher in STEMI patients with IRA occluded than in those with patent ones. At a cutoff value of 36.9 mg/L, SAA had a sensitivity of 63.0% and a specificity of 90.6% (area under the ROC curve [AUC] =.833, 95% CI:.793-.873, P <.001). Multivariate logistic regression analysis showed that SAA was an independent predictor of IRA patency in STEMI patients before PCI (odds ratio [OR] = 1.041, 95% CI: 1.020-1.062, P <.001). SAA can be used as a potential predictor of IRA patency in STEMI patients before PCI. [ABSTRACT FROM AUTHOR]

The identification of novel, robust biomarkers for the diagnosis of rheumatic diseases (RDs) and the presence of active disease might facilitate early treatment and the achievement of favourable long-term outcomes. We conducted a systematic review and meta-analysis of studies investigating the acute phase reactant, serum amyloid A (SAA), in RD patients and healthy controls to appraise its potential as diagnostic biomarker. We searched PubMed, Scopus, and Web of Science from inception to 10 April 2024 for relevant studies. We evaluated the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024537418). In 32 studies selected for analysis, SAA concentrations were significantly higher in RD patients compared to controls (SMD = 1.61, 95% CI 1.24–1.98, p < 0.001) and in RD patients with active disease compared to those in remission (SMD = 2.17, 95% CI 1.21–3.13, p < 0.001). Summary receiving characteristics curve analysis showed a good diagnostic accuracy of SAA for the presence of RDs (area under the curve = 0.81, 95% CI 0.78–0.84). The effect size of the differences in SAA concentrations between RD patients and controls was significantly associated with sex, body mass index, type of RD, and study country. Pending the conduct of prospective studies in different types of RDs, the results of this systematic review and meta-analysis suggest that SAA is a promising biomarker for the diagnosis of RDs and active disease. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) proteins are highly conserved lipoproteins that are notoriously involved in the acute phase response and systemic amyloidosis, but their biological functions are incompletely understood. Recent work has shown that SAA proteins can enter the brain by crossing the intact blood–brain barrier (BBB), and that they can impair BBB functions. Once in the central nervous system (CNS), SAA proteins can have both protective and harmful effects, which have important implications for CNS disease. In this review of the thematic series on SAA, we discuss the existing literature that relates SAA to neuroinflammation and CNS disease, and the possible roles of the BBB in these relations. [ABSTRACT FROM AUTHOR]

In older horses, basal metabolic rate decreases, and plasma metabolite and hormone concentrations related to energy metabolism change. The occurrence of age-related diseases, which increases in old animals, may enhance inflammatory reactivity (inflammaging). Finding the appropriate treatment for inflammaging at an early stage may prevent various age-related diseases. Changes in metabolite and hormone concentrations and enzyme activities involved in energy metabolism in the plasma of clinically healthy riding horses of various ages were measured to identify biomarkers of inflammaging (persistent low-grade inflammation that occurs with aging). All horses were clinically healthy, and their body condition scores (BCSs) were 4 or 5 (9-point scale). Plasma triglyceride (TG), total cholesterol (T-Cho), blood urea nitrogen (BUN), insulin concentrations, malondialdehyde (MDA), and serum amyloid A (SAA) concentrations generally increased with age. Adiponectin concentrations, plasma superoxide dismutase (SOD), and leukocyte AMP-activated protein kinase (AMPK) activities decreased, while plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutathione peroxidase (GPx) remained unchanged as horses aged. Although riding horses that partake in continuous exercise seems to be less likely to develop inflammaging, horses over 17 years of age tend to show proinflammatory signs with disordered lipid metabolism. In riding horses, SAA, in combination with other markers, may be a useful biomarker for inflammaging and dysregulated lipid metabolism in aging horses. [ABSTRACT FROM AUTHOR]

In this study, the changes in concentrations of serum amyloid A (SAA) induced by orchidectomy, Burdizzo castration, and in-situ spermatic cord ligation in Red Sokoto bucks were evaluated. Sixteen (16) Red Sokoto bucks, 6 months to one year old and weighing between 11kg and 12 kg, were randomly divided into 4 groups (A-D), each comprising 4 bucks. Bucks in group A were castrated using the Burdizzo method, B in-situ spermatic cord ligation, and C orchidectomy while group D served as control. Blood was collected from each buck, serum was harvested and analyzed for SAA at 0, 4, 8, 12, 15, 20, 24, 36, 48 and 72 hours post-castration. Results revealed significant increase (p=0.028) in the levels of SAA in all castrated goats from 4 hours post-castration, reaching peak concentration at 20 hours post-castration with the highest recorded in goats castrated by orchidectomy (63.34 ± 1.49 pg/mL; 120.44 ± 3.74 pg/mL), followed by in-situ spermatic cord ligation (25.08 ± 2.19 pg/mL; 109.77 ± 2.97 pg/mL) and then Burdizzo (61.36 ± 2.63 pg/mL; 87.29 ± 3.92 pg/mL). This was followed by a significant (p=0.041) decrease by 24 hours post-castration and non-significant (p=0.101) fluctuations up to 72 hours post-castration in all castrated bucks. In conclusion, all the castration methods induced changes in serum concentration of SAA, which was less marked in Burdizzo and in-situ spermatic cord ligation compared to orchidectomy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate diagnostic accuracy of point-of-care Serum Amyloid A (POC-SAA) and its comparison with procalcitonin for diagnosis of neonatal sepsis. Methods: The present diagnostic accuracy study consecutively recruited neonates with suspected sepsis. Blood samples for sepsis screen, culture, high sensitivity C-reactive protein (CRP) (hs-CRP, as a part of sepsis screen), procalcitonin and POC-SAA were collected before starting antibiotics. The optimum cut-off level of biomarkers (POC-SAA and procalcitonin) was determined by receiver-operating-characteristics curve (ROC) analysis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of POC-SAA and procalcitonin were derived for 'clinical sepsis (neonates with suspected sepsis and either positive sepsis screen and/or blood culture)' and 'culture positive sepsis' (neonates with suspected sepsis and positive blood culture). Results: Seventy-four neonates with mean±SD gestational age of 32.8±3.7 wk were evaluated for suspected sepsis, of which the proportion of 'clinical sepsis' and 'culture positive sepsis' was 37.8% had 16.2%, respectively. At a cut-off of 25.4 mg/L, POC-SAA had sensitivity, specificity, PPV and NPV of 53.6%, 80.4%, 62.5% and 74.0%, respectively for diagnosis of clinical sepsis. The sensitivity, specificity, PPV and NPV of POC-SAA for detection of culture positive sepsis were 83.3%, 61.3%, 29.4% and 95.0%, respectively at a cut-off of 10.3 mg/L. There was no significant difference in the diagnostic accuracy of biomarkers for detection of culture positive sepsis (area under the curve, AUC of POC-SAA vs. procalcitonin vs. hs-CRP: 0.72 vs. 0.85 vs. 0.85; p = 0.21). Conclusions: POC-SAA is comparable to procalcitonin and hs-CRP for diagnosis of neonatal sepsis. [ABSTRACT FROM AUTHOR]

Senescent cells have a profound impact on the surrounding microenvironment through the secretion of numerous bioactive molecules and inflammatory factors. The induction of therapy-induced senescence by anticancer drugs is known, but how senescent tumor cells influence the tumor immune landscape, particularly neutrophil activity, is still unclear. In this study, we investigate the induction of cellular senescence in breast cancer cells and the subsequent immunomodulatory effects on neutrophils using the CDK4/6 inhibitor palbociclib, which is approved for the treatment of breast cancer and is under intense investigation for additional malignancies. Our research demonstrates that palbociclib induces a reversible form of senescence endowed with an inflammatory secretome capable of recruiting and activating neutrophils, in part through the action of interleukin-8 and acute-phase serum amyloid A1. The activation of neutrophils is accompanied by the release of neutrophil extracellular trap and the phagocytic removal of senescent tumor cells. These findings may be relevant for the success of cancer therapy as neutrophils, and neutrophil-driven inflammation can differently affect tumor progression. Our results reveal that neutrophils, as already demonstrated for macrophages and natural killer cells, can be recruited and engaged by senescent tumor cells to participate in their clearance. Understanding the interplay between senescent cells and neutrophils may lead to innovative strategies to cope with chronic or tumor-associated inflammation. [ABSTRACT FROM AUTHOR]

Objective: Our previous study revealed that serum amyloid A (SAA) levels in polyp tissues could serve as a biomarker for the prediction of corticosteroid insensitivity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, their association with disease control status in the patients after endoscopic sinus surgery remains to be assessed. Methods: Polyp tissues and control uncinate process mucosa were collected from 48 patients with CRSwNP and 10 healthy control subjects. SAA expression was examined using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of SAA in nasal polyps. The clinical characteristics of 2 CRSwNP subtypes (SAAhigh and SAAlow) were evaluated. Results: The SAA expression levels in polyp tissues were significantly elevated both in non-eosinophilic and eosinophilic CRSwNP as compared to the healthy controls. In patients with CRSwNP, the tissue SAA level was significantly higher in the disease-controlled patients than those of the partly controlled and uncontrolled. ROC curve analysis revealed that a cut-off value of 114.9 ng/mL for the tissue SAA level predicted the patients with disease-controlled status with 93.33% sensitivity and 63.64% specificity (AUC =.8727, P <.001). Furthermore, The SAAhigh subgroup showed higher tissue eosinophil numbers and percentage of the disease-controlled patients compared to the SAAlow subgroup. Conclusions: Our findings suggest that measurements of SAA in polyp tissues may provide useful information for evaluating CRSwNP conditions, especially identifying the CRSwNP patients with disease-controlled status after endoscopic sinus surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Pregnancy-associated glycoproteins (PAG) secreted from fetoplacental binucleate cells are used in clinical practice for the early detection of bovine pregnancy. This study examined the postpartum PAG concentration to monitor binucleated cell clearance during postpartum uterine repair. PAG concentration was correlated with inflammatory parameters (serum amyloid A and milk amyloid A), postpartum inflammatory conditions (mastitis, ketosis, and follicular cysts), and FOXP3 gene-related repeat breeders. Excessive inflammation occurring during the postpartum period may reduce PAG concentration gradually. Clarifying the mechanism of decreased PAG concentration during the postpartum period has a beneficial effect on improving reproductive efficiency, performance, and reproduction aspects. We evaluated the relationship between decreased pregnancy-associated glycoprotein (PAG) levels, inflammatory parameters (serum amyloid A [SAA] and milk amyloid A [MAA]), postpartum inflammatory conditions (mastitis, ketosis, and follicular cysts), and the FOXP3 gene. Nineteen Holstein-Friesian cows were included in this study. Up to approximately eight weeks after delivery, weekly health examinations were performed for mastitis and ketosis, and reproductive organ ultrasonography was performed. The decreasing PAG rate was negatively correlated with SAA concentration (r = −0.493, p = 0.032). Cows with mastitis exhibited a slower trend of PAG decrease (p = 0.095), and a greater percentage of these cows had MAA concentrations above 12 µg/mL (p = 0.074) compared with those without mastitis. A negative correlation, although nonsignificant (r = −0.263, p = 0.385), was observed between the day-open period and decreased PAG rate. The day-open period was correlated with the presence or absence of follicular cysts (p = 0.046). Four cows that developed follicular cysts were homozygous for the G allele of the FOXP3 gene related to repeat breeders. These results indicate a relationship between a decreased PAG rate and inflammatory status during the postpartum period. Thus, suppressing inflammation during the perinatal period may improve reproductive efficiency in the dairy industry. [ABSTRACT FROM AUTHOR]

Copyright of Guangdong Medical Journal is the property of Guangdong Medical Journal Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Serum amyloid A (SAA) is a highly conserved acute‐phase protein that plays roles in activating multiple pro‐inflammatory pathways during the acute inflammatory response and is commonly used as a biomarker of inflammation. It has been linked to beneficial roles in tissue repair through improved clearance of lipids and cholesterol from sites of damage. In patients with chronic inflammatory diseases, elevated levels of SAA may contribute to increased severity of the underlying condition. The majority of circulating SAA is bound to lipoproteins, primarily high‐density lipoprotein (HDL). Interaction with HDL not only stabilizes SAA but also alters its functional properties, likely through altered accessibility of protein–protein interaction sites on SAA. While high‐resolution structures for lipid‐free, or apo‐, forms of SAA have been reported, their relationship with the HDL‐bound form of the protein, and with other possible mechanisms of SAA binding to lipids, has not been established. Here, we have used multiple biophysical techniques, including SAXS, TEM, SEC‐MALS, native gel electrophoresis, glutaraldehyde crosslinking, and trypsin digestion to characterize the lipid‐free and lipid‐bound forms of SAA. The SAXS and TEM data show the presence of soluble octamers of SAA with structural similarity to the ring‐like structures reported for lipid‐free ApoA‐I. These SAA octamers represent a previously uncharacterized structure for lipid‐free SAA and are capable of scaffolding lipid nanodiscs with similar morphology to those formed by ApoA‐I. The SAA–lipid nanodiscs contain four SAA molecules and have similar exterior dimensions as the lipid‐free SAA octamer, suggesting that relatively few conformational rearrangements may be required to allow SAA interactions with lipid‐containing particles such as HDL. This study suggests a new model for SAA–lipid interactions and provides new insight into how SAA might stabilize protein‐lipid nanodiscs or even replace ApoA‐I as a scaffold for HDL particles during inflammation. [ABSTRACT FROM AUTHOR]

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Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease‐related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new‐onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme‐linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo‐SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new‐onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL‐6, and IL‐17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late‐onset MG (LOMG) than in early‐onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo‐SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients. [ABSTRACT FROM AUTHOR]

The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of von Willebrand factor (VWF), platelet factor 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), and platelet endothelial cell adhesion molecule (PECAM-1) in the soluble part of the blood. It was noteworthy that the mean level of α-2 antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We conclude that presence of microclotting, together with relatively high levels of six biomarkers known to be key drivers of endothelial and clotting pathology, points to thrombotic endothelialitis as a key pathological process in Long COVID. [ABSTRACT FROM AUTHOR]

The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL‐6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL‐6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL‐6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll‐like receptor (TLR) ligands, pathogen‐associated and damage‐associated molecular pattern molecules. In vitro, TLR ligands induced IL‐6 expression via NF‐κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL‐6 via TLR1/2 and NF‐κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR‐mediated persistent skin inflammation might increase the risk of IL‐6‐related systemic complications, including RDEB. [ABSTRACT FROM AUTHOR]

Objective: This study investigated whether serum amyloid A (AA) levels can be used as a biomarker in patients with threatened abortion. Material and Methods: This prospective cohort study was conducted at the Antalya Training and Research Hospital, Department of Obstetrics and Gynecology, Türkiye, between April and October 2023. Eighty‐eight pregnant women, 44 diagnosed with threatened miscarriage (Group 1) and 44 healthy individuals (Group 2), were included in the study. Sociodemographic, obstetric, and laboratory parameters were compared between the groups. Results: No statistically significant differences were observed between the groups in terms of sociodemographic data (age, body mass index, education level, economic status, occupation status, smoking, and alcohol consumption). However, obstetric characteristics (number of pregnancies, living children, miscarriages, dilatation and curettage, gestational age on admission, and fetal crown‐rump length) and laboratory values including complete blood count, hematocrit, leukocyte, neutrophil, lymphocytes, platelet, hs‐C‐reactive protein, neutrophil‐lymphocyte and platelet‐lymphocyte ratio (p >.05), and serum AA values (7.49 ± 3.07 in Group 1 vs. 9.46 ± 4.80 in Group 2, p =.024) differed significantly. Receiver operating characteristic analysis showed that the area under the curve (AUC: 0.662) was statistically significant for serum AA (p =.032), with a cut‐off value of ≥7.51 (95% [confidence interval] 0.516−0.749, sensitivity 65%, specificity 51%). The positive predictive value of serum AA for threatened miscarriage was 56.8%, and the negative predictive value 59.4%. Conclusion: This study shows that serum AA can be used as a biomarker in the diagnosis of threatened miscarriage. Prospective studies involving more participants are now needed to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Anemia is a common complication of total hip arthroplasty (THA). In this study, we evaluated the preoperative risk factors for postoperative anemia after THA and developed a nomogram model based on related preoperative and intraoperative factors. Methods: From January 2020 to May 2023, 927 THA patients at the same medical center were randomly assigned to either the training or validation cohort. The correlation between preoperative and intraoperative risk factors and postoperative anemia after THA was evaluated using univariate and multivariate logistic regression analysis. A nomogram was developed using these predictive variables. The effectiveness and validation for the clinical application of this nomogram were evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Through univariate and multivariate logistic regression analysis, 7 independent predictive factors were identified in the training cohort: Lower body mass index (BMI), extended operation time, greater intraoperative bleeding, lower preoperative hemoglobin level, abnormally high preoperative serum amyloid A (SAA) level, history of cerebrovascular disease, and history of osteoporosis. The C-index of the model was 0.871, while the AUC indices for the training and validation cohorts were 84.4% and 87.1%, respectively. In addition, the calibration curves of both cohorts showed excellent consistency between the observed and predicted probabilities. The DCA curves of the training and validation cohorts were high, indicating the high clinical applicability of the model. Conclusions: Lower BMI, extended operation time, increased intraoperative bleeding, reduced preoperative hemoglobin level, elevated preoperative SAA level, history of cerebrovascular disease, and history of osteoporosis were seven independent preoperative risk factors associated with postoperative anemia after THA. The nomogram developed could aid in predicting postoperative anemia, facilitating advanced preparation, and enhancing blood management. Furthermore, the nomogram could assist clinicians in identifying patients most at risk for postoperative anemia. [ABSTRACT FROM AUTHOR]

The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better biomarker of disease activity in inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). This retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR), the platelet count and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for SAA concentrations if an FC concentration measurement was available from ±14 days to collection of the serum sample. Three hundred and six serum samples from 265 patients (166 with Crohn's disease, 91 with ulcerative colitis and 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, NLR, platelet count and the Simple Clinical Colitis Activity Index (SCCAI). The cut-off for SAA serum concentration at 4.55 mg/L achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations. [ABSTRACT FROM AUTHOR]

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the clinical and laboratory characteristics of early-onset familial Mediterranean fever patients (EOFPs), adult-onset familial Mediterranean fever (FMF) patients (AOFPs), and late-onset FMF patients (LOFPs). Materials and Methods: This study included a total of 202 FMF patients aged 18 years and above. Mediterranean fever (MEFV) gene mutations, demographic data, clinical characteristics, medications patients are on, neutrophil to absolute lymphocyte ratio (NLR), and C-reactive protein (CRP) levels obtained during an attack period, and three weeks after the attack were recorded. Based on the age of symptom onset, patients were divided into three groups: <20 years (EOFPs), 20--39 years (AOFPs), and ≥40 years (LOFPs). Results: The most common symptom was abdominal pain, followed by fever. Fever was statistically significantly more common in EOFPs compared to LOFPs (p=0.001). Most patients with the M694V homozygous mutation had a disease onset below 20 years of age, whereas no compound heterozygous mutation was found in LOFPs. The body mass index (BMI) in EOFPs was lower than in AOFPs and LOFPs (p=0.002). In the attack-free group, patients with the M694V homozygous mutation had significantly higher NLRs (median, 2.36 vs. 2.01, p=0.042). Conclusion: LOFPs had a milder form of the disease with less frequent abdominal pain and fever. We would like to advise clinicians that the NLR can be used to detect acute and subacute inflammation, especially in patients with the M694V homozygous mutation among EOFPs [ABSTRACT FROM AUTHOR]

Aims/Introduction: Serum amyloid A (SAA) is an acute phase reactive protein that plays a vital role in the early diagnosis, risk prediction, efficacy observation and prognosis evaluation of infectious diseases. This study aimed to assess the association between SAA levels and the prognosis of patients with coronavirus disease 2019 (COVID‐19) and diabetes. Materials and Methods: We carried out this retrospective cohort study from March 2022 to May 2022. The population was stratified by tertiles of SAA levels: low (<8.5 mg/L), medium (8.5–36 mg/L) and high (>36 mg/L). The primary outcome was whether the patient developed severe COVID‐19, and secondary outcomes included the need for invasive mechanical ventilation and length of hospital stay. Logistic regression analyses were carried out to identify risk factors affecting the prognosis of patients with COVID‐19 and diabetes. Results: We analyzed 910 diabetes patients with COVID‐19. The median age of the patients was 69 years, and 52.3% were men. As SAA levels increased, the proportion of severe COVID‐19 (6.3% vs 7.3% vs 22.8%, P < 0.001) and the proportion of invasive mechanical ventilation also increased among the three groups. Patients with high SAA levels had a longer length of hospital stay compared with patients with medium SAA and low SAA levels. Univariate logistic regression analysis showed that SAA >36 mg/L further increased the odds ratio to 4.423 (P < 0.001) for the development of severe COVID‐19 compared with low SAA. Multivariate logistic regression analysis, adjusted for age and sex, confirmed that SAA >36 mg/L remained an independent risk factor for the development of severe COVID‐19 (adjusted odds ratio 3.038, P < 0.001). Conclusions: SAA levels are strongly associated with poor prognosis in patients with COVID‐19 and diabetes. [ABSTRACT FROM AUTHOR]

Objective: In this study were investigated serum paraoxonase, haptoglobin, tumor necrosis factor-α, acetylcholinesterase, serum amyloid A, nonesterifie fatty acids, glucose, beta hydroxybutyric acid, total protein, aspartat aminotransferase, gama glutamil transferase, cholesterol and triglyceride in ewes with pregnancy toxemia. Materials and Methods: This study material consisted 10 control and 10 group with pregnancy toxemia, total 20 merino hybrid ewes at aged between 2-6 years. Results: The analysis of blood serum samples revealed that serum amyloid A (SAA), haptoglobin (HPT), tumor necrosis factor-α (TNF), paraoxonase (PON1), acetylcholinesterase (ACHE), aspartat aminotransferase (AST), gama glutamil transferase (GGT) and cholesterol did not differ statistically significant between two groups although SAA, HPT, TNF, PON1, ACHE, AST, GGT levels were higher in ewes with pregnancy toxemia when compared to healthy ewes. Beta hydroxybutyric acid (BHBA) and nonesterifie fatty acids (NEFA) (p<0.001), triglyceride and total protein (p<0.01) increased that glucose (p<0.001) levels decreased in sheep with pregnancy toxemia compared with healthy ewes. Conclusion: Acetylcholinesterase, paraoxonase, haptoglobin, tumor necrosis factor-α, serum amyloid A concentration researched may prove beneficial laboratory findings disease in sheep with pregnancy toxemia. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD. SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers. During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40–547.25] vs 230.85 [105.40–490.00] mg/L; p =.008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p <.05); however, the lymphocytes, platelets, serum sodium levels, and duration of fever before IVIG therapy were significantly lower (p <.05). There was no significant difference in SAA levels between patients with KD with and without CALs. Binary logistic regression analysis showed that SAA (p =.008), neutrophils (p <.001), total bilirubin (p =.001), platelet count (p =.004), and serum sodium level (p =.019) were independent factors influencing IVIG resistance. The optimal cutoff value of SAA for IVIG resistance prediction was 252.45 mg/L, with a corresponding clinical sensitivity of 69.8% and specificity of 54.4%. Based on receiver operating characteristic (ROC) curve analyses, the area under the curve (AUC) of combined detection with these five indicators was 0.800, clinical sensitivity was 69.8%, and specificity was 76.2%. In the prospective data, the sensitivity, specificity, and accuracy of SAA for identifying IVIG resistance KD were 77.8%,69.0%, and 70.0%, respectively. Compared with IVIG- responsive group and healthy children, the levels of IL-6 was upregulated significantly in IVIG-resistant group through cytokine microarrays. SAA may be a potential biomarker for predicting IVIG responsiveness to KD, Combined detection of SAA levels, total bilirubin, neutrophil count, platelet count, and serum sodium levels is superior to that of any other single indicator for predicting IVIG resistance in KD. And elevated SAA may accompany with IL-6 in KD patients, its use in clinical practice may be helpful for treatment management. [ABSTRACT FROM AUTHOR]

Backgrounds: The available literature on the correlation between serum amyloid A (SAA) and prognosis of chronic kidney disease (CKD) are limited, and the findings from existing studies are inconclusive. This meta-analysis aimed to evaluate the available evidence regarding the link between SAA and risks of all-cause and cardiovascular mortality in CKD patients. Additionally, we aimed to investigate the potential dose-response relationships, provided that adequate data is accessible. Methods: Pubmed and Embase were searched for related literature (last update: 12 July 2023). The pooled effect estimates were calculated using random- or fixed-effects models depending on heterogeneity among studies. Results: This meta-analysis incorporated 8 studies encompassing 2331 CKD patients. The findings revealed an 85% increase in all-cause mortality risk [hazard risk (HR) 1.85, 95% confidence interval (CI) 1.29-2.65] and a 39% increase in cardiovascular mortality risk (HR 1.07, 95% CI 1.07-1.80) when comparing the highest tertile of baseline SAA levels to the lowest tertile. Furthermore, a positive linear relationship between SAA and all-cause mortality risk was observed (Pnon-linearity = 0.959), with a 17.7% increase in risk for each 10 mg/L SAA increase (HR 1.177, 95% CI 1.055-1.313). Similarly, a linear relationship between SAA and cardiovascular mortality risk was identified (Pnon-linearity = 0.477) with a 19.3% increase in risk for each 10 mg/L SAA increase (HR 1.193, 95% CI 1.025-1.388). Conclusions: This meta-analysis provided evidence that SAA levels are positively and linearly associated with risks of all-cause and cardiovascular mortality among CKD patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic kidney disease (CKD) is a major cause of morbidity and mortality in cats. Despite the increasing worldwide interest in feline CKD, the specific role of systemic inflammation in these patients remains poorly defined. The aim of the present prospective study was to assess serum amyloid A (SAA) and erythrocyte sedimentation rate (ESR) levels as markers of inflammation in cats diagnosed with CKD at IRIS stages 2–4. The results indicate a systemic inflammatory state associated with feline CKD, as both markers showed significantly higher levels in affected animals than in healthy ones. Compared to SAA, the rise in ESR appears to be more closely linked to advanced stages of the disease and could, therefore, correlate with the uremic condition. This prospective study aimed to evaluate inflammatory status in cats affected by chronic kidney disease (CKD) at IRIS stages 2–4, using serum amyloid A (SAA) and the erythrocyte sedimentation rate (ESR) as inflammatory markers. Thirty-two cats with CKD and ten clinically healthy cats (i.e., control group) were enrolled. The recording of signalment data, complete physical examinations, and abdominal ultrasonography were performed for each animal. Additionally, ESR levels, complete blood count, clinical chemistry (including SAA determination), serum protein electrophoresis, and complete urinalysis were executed. This study's results showed that mean ESR and SAA concentrations in cats with CKD were statistically higher compared to those of the control group (p = 0.0005 and p = 0.007, respectively). The SAA concentration was significantly increased at IRIS stages 2, 3, and 4 compared to the control group. Meanwhile, the ESR was significantly higher in cats at IRIS stages 3 and 4 (p = 0.0003 and p = 0.0007, respectively), but not at IRIS stage 2, compared to the control group. These results provide evidence that feline CKD is associated with a systemic inflammatory status. Moreover, the rise in ESR appears to be more linked to advanced stages of the disease and could, therefore, correlate with the uremic condition. [ABSTRACT FROM AUTHOR]

Background: Obesity is a chronic inflammatory condition and this meta-analysis evaluated the impact of bariatric surgery on SAA. Methods: Studies included all types of bariatric surgery where SAA was measured before and after the surgical procedure. Results: Meta-analysis of 11 clinical studies (n = 394 individuals) confirmed a significant reduction in SAA following bariatric surgery (SMD: − 0.971, 95% CI: − 2.721, 0.779, p < 0.001). Meta-regression did not show any association between the changes in BMI and the absolute difference in SAA levels. No relationship between the changes in SAA and the length of follow-up was found. Conclusion: Bariatric surgery significantly improved SAA. The decrease in SAA was not related to time after surgery or changes in BMI. Bariatric surgery may thus have an independent effect on SAA. [ABSTRACT FROM AUTHOR]

The diagnosis of ewes' pregnancy status at an early stage is an efficient way to enhance the reproductive output of sheep and allow producers to optimize production and management. The techniques of proteomics and metabolomics have been widely used to detect regulatory factors in various physiological processes of animals. The aim of this study is to explore the differential metabolites and proteins in the serum of pregnant and non-pregnant ewes by proteomics and metabolomics. The serum of ewes at 21, 28 and 33 days after artificial insemination (AI) were collected. The pregnancy stratus of the ewes was finally determined through ultrasound examination and then the ewes were grouped as Pregnant (n = 21) or N on-pregnant (n = 9). First, the serum samples from pregnant or non-pregnant ewes at 21 days after AI were selected for metabolomic analysis. It was found that the level of nine metabolites were upregulated and 20 metabolites were downregulated in the pregnant animals (p < 0.05). None of these differential metabolomes are suitable as markers of pregnancy due to their small foldchange. Next, the proteomes of serum from pregnant or non-pregnant ewes were evaluated. At 21 days after AI, the presence of 321 proteins were detected, and we found that the level of three proteins were upregulated and 11 proteins were downregulated in the serum of pregnant ewes (p < 0.05). The levels of serum amyloid A (SAA), afamin (AFM), serpin family A member 6 (SERPINA6) and immunoglobulin-like domain-containing protein between pregnant and non-pregnant ewes at 21-, 28- and 33-days post-AI were also analyzed via enzyme-linked immunosorbent assay (ELISA). The levels of SAA and AFM were significantly higher in pregnant ewes than in non-pregnant ewes, and could be used as markers for early pregnancy detection. Overall, our results show that SAA and AFM are potential biomarkers to determine the early pregnancy status of ewes. [ABSTRACT FROM AUTHOR]

Background Unicentric Castleman's disease (UCD), a lymphoproliferative disorder characterized by enlargement of the lymph nodes, is a rare cause of Amyloid-A amyloidosis. While patients usually present with impaired kidney function and proteinuria, heart involvement is neither common nor the main cause of signs and symptoms. Case summary We present a patient who was admitted to the hospital for impaired exercise capacity. Diagnostic work-up revealed severe left ventricular hypertrophy suggestive of cardiac amyloidosis. Although Congo red staining of endomyocardial biopsies was initially negative, subsequent immunohistochemical staining against serum amyloid A finally confirmed the diagnosis of cardiac amyloidosis. 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed a tumour located in dorsal of the duodenum. Fine-needle aspiration biopsy of the tumour was suggestive but could not confirm the presence of UCD beyond reasonable doubt. Rapid worsening of heart failure symptoms warranted urgent surgical tumourectomy, which resulted in immediate post-operative lowering of serum amyloid protein. However, post-operative cardiogenic shock could not be stabilized even with veno-arterial extracorporeal membrane oxygenation, and the patient eventually died. The UCD of the hyaline vascular (HV) subtype was confirmed by pathologic work-up of the excised tumour. Discussion This case report presents for the first time a patient with malignant cardiac Amyloid-A amyloidosis caused by unicentric Castleman's disease of the HV subtype. Since the disease progresses swiftly, rapid diagnosis is essential for potential curative treatment. [ABSTRACT FROM AUTHOR]

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Copyright of Pferdeheilkunde is the property of Hippiatrika Verlag GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: During inflammation, acute-phase proteins or leukocyte toxic changes may be observed in dogs and cats, aiding in the diagnosis and prognosis of inflammatory diseases. Leukocyte ratios are generally evaluated in human medicine for the diagnosis and prognosis of inflammatory and neoplastic conditions. Recently, some of these ratios have been evaluated in dogs and cats, showing useful results; however, their relationship to routinely measured markers of inflammation has never been investigated in cats. The present study showed changes in neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios correlated with those of other markers of inflammation in cats, such as serum amyloid A, albumin, globulins, and albumin-to-globulin ratio. The values of NLR and MLR in cats with no changes in parameters indicative of inflammation were significantly lower when compared with those of cats with increased SAA or hypoalbuminemia. These results demonstrate that leukocyte ratios can be valuable markers of inflammation in cats. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios have been proposed as diagnostic and prognostic markers for neoplastic and inflammatory diseases in dogs and cats. The aim of this retrospective preliminary study was to evaluate the relationship between these ratios and markers of inflammation routinely measured in cats. A total of 275 cats were enrolled. Complete blood count, serum amyloid A (SAA), albumin, globulin, and albumin-to-globulin ratio (AGR) data were analyzed, as well as the presence of leukocyte alterations considered suggestive of inflammation (LAI: neutrophils left shift, toxic neutrophils, and reactive lymphocytes) evaluated in blood smears. The NLR and MLR correlated positively with SAA and globulins and negatively with albumin and AGR. Higher NLR and MLR were found in cats with increased SAA and globulins and decreased albumin and AGR. The PLR correlated negatively with albumin and AGR. A higher PLR was found in cats with hypoalbuminemia. Cats with LAI had higher NLR, MLR, and PLR. In cats with no changes in parameters indicative of inflammation, 11.25, 0.42, and 528.3 were identified as upper limits for NLR, MLR, and PLR, respectively. In conclusion, the NLR, MLR, and PLR act as good inflammatory markers easily evaluated by routine hematology. [ABSTRACT FROM AUTHOR]

Simple Summary: The results of this test suggest that serum amyloid A is a sensitive and reliable index of inflammation without disease specificity in Japanese Black cattle. Moreover, the serum amyloid A concentration can evaluate the prognosis and therapeutic effects in diseased cattle more objectively. This study investigated the concentration of serum amyloid A (SAA), an acute phase protein, in Japanese Black cattle. Four practical trials were performed to evaluate the transition of SAA and sialic acid before and after dehorning, the relationship between the SAA concentration and other blood test parameters, the SAA dynamics in the diseased cattle, and the blood test results, including the SAA concentrations, of the two cases with a follow-up. The SAA concentration increased with dehorning but decreased 7 days after dehorning. The SAA concentration is positively correlated with the α-globulin, sialic acid, and fibrinogen concentrations and negatively correlated with the serum iron concentration. The SAA concentration in the deceased herd was significantly higher than that in the cured outcome herd. In addition, the SAA concentration in the cured group decreased significantly from the first test to retesting but increased significantly in the disuse group. Thus, SAA is a sensitive index of inflammation and a monitoring tool in Japanese Black cattle, and its measurement is considered useful in clinical practice. [ABSTRACT FROM AUTHOR]

Obesity has been identified as a serious health concern in domestic cats. Feline mammary cancer (FMC) is also a concern, as it is highly prevalent and aggressive. Considering the identified connection between obesity and breast cancer, it is worthwhile to investigate the potential obesity–cancer relationship in FMC. This review investigated the association between adipokines and other obesity-associated molecules and FMC, with the aim of identifying gaps in the current literature for future research. Based on the reports to date, it was found that tissue concentrations of leptin, serum concentrations of leptin receptor, serum amyloid A, and estrogen correlate positively with FMC, and serum concentrations of leptin correlate negatively with FMC. The roles of adiponectin and prolactin in FMC development were also investigated, but the reports are either lacking or insufficient to suggest an association. Numerous research gaps were identified and could be used as opportunities for future research. These include the need for studies on additional cohorts to confirm the association of leptin/leptin receptor and serum amyloid A with FMC, and to address the role of adiponectin and prolactin in FMC. It is also important to investigate the genetic determinants of FMC, evaluate the use of molecular-targeted therapies in FMC, and exploit the enrichment of the triple-negative immunophenotype in FMC to address current clinical needs for both human triple-negative breast cancer and FMC. Finally, mechanistic studies with any of the molecules reviewed are scarce and are important to generate hypotheses and ultimately advance our knowledge and the outcome of FMC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the value of single or combined detection of procalcitonin (PCT), interleukin-6 (IL-6), serum amyloid A (SAA) and c-reactive protein (CRP) in the differential diagnosis of simple and strangulated intestinal obstruction. Methods: This retrospectively study collected 61 patients with intestinal obstruction. The patients were classified into the group of simple or strangulated intestinal obstruction according to operation. The age, sex, basic diseases, lesion sites and inflammatory indicators such as PCT, IL-6, SAA and CRP in two groups were collected and analyzed. The Students' T-test and the Mann-Whitney U test were used to analyze normally and non-normally distributed data, respectively. The categorical variable was analyzed by the chi-square test. The receiver-operating characteristic (ROC) curve and the area under the curve (AUC) were used to predict the differential diagnostic value of single and combined detection of the above clinical inflammatory indicators. Results: The serum levels of PCT, IL-6, SAA and CRP of the strangulated group were significantly higher than those of the simple group (p <.05). The areas under the ROC curve (AUC) were 0.907 for PCT, 0.712 for IL-6, 0.723 for SAA and 0.681 for CRP. With the cutoff values of PCT (0.24 ng/L), IL-6 (19.55 pg/L), SAA (282.50 mg/L) and CRP (63.00 mg/L), the sensitivity and specificity were 86.40% and 87.20% for PCT, 68.20% and 76.90% for IL-6, 59.10% and 87.20% for SAA, 63.60% and 87.20% for CRP, respectively. And the sensitivity and specificity were 86.40% and 89.70% for combined model. The differences between PCT and the combined model are tiny and neither clinically nor statistically significant. Conclusions: For discriminating strangulated intestinal obstruction from simple intestinal obstruction, PCT alone may be the preferred approach due to its simplicity. [ABSTRACT FROM AUTHOR]

Objectives: Inflammation shows a notable relationship to acute ischemic stroke's (AIS) occurrence and prognosis. However, existing research has confirmed that serum amyloid A (SAA) is an inflammatory biomarker. The aim of this paper was to investigate the association between SAA and the three-month clinical results of acute AIS patients after intravenous thrombolysis (IVT). Methods: The evaluation of AIS patients with complete medical records was carried out by prospectively investigating patients hospitalized in our department between January 2020 and February 2023. The SAA levels were examined with the use of an immunosorbent assay kit that shows a relationship with the enzyme (Invitrogen Corp). Patients were dichotomized into favorable (mRS score of 0, 1 or 2) and unfavorable (mRS score of 3, 4, 5, or 6) results with the use of the modified Rankin Scale (mRS). Results: A total of 405 AIS patients who were subjected to IVT therapy were prospectively covered. To be specific, 121 (29.88%) patients had an unfavorable prognosis during the follow-up for 3 months. On that basis, patients achieving unfavorable results gained notably greater SAA levels (39.77 (IQR 38.32-46.23) vs.31.23 (IQR 27.44-34.47), p < 0.001) during hospitalization in comparison to patients with a better result. In the analysis with multiple variates, SAA was adopted to achieve the independent prediction of the three-month unfavorable clinical results of acute AIS patients after IVT [OR:2.874 (95% CI, 1.764-4.321), p < 0.001]. When the fundamental confounding factors were regulated, the odds ratio (OR) of unfavorable prognosis after AIS patients undergoing IVT therapy was 4.127 (95% CI = 1.695-10.464, p = 0.032) for the maximum tertile of SAA in terms of the minimal tertile. With an AUC of 0.703 (95% CI, 0.649-0.757), SAA revealed a notably more effective discriminating capability in terms of CRP, NLR, EMR, and WBC. SAA as a predictor in terms of the prediction of three-month unfavorable results after AIS patients undergoing IVT therapy achieved specificity and sensitivity of 84.45% and 77.23%, as well as an optimal cut-off value (COV) of 37.39. Conclusion: SAA level that is up-regulated during hospitalization is capable of serving as an effective marker in terms of the prediction of unfavorable threemonth results in AIS patients after IVT. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Biochemistry is the property of Society of Medical Biochemists of Serbia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Arteriosclerosis is the property of Chinese Journal of Arteriosclerosis Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diagnostic techniques based on biomolecules have application potential that can be realized in many fields, such as disease diagnosis, bioprocess imaging, food/beverage industries, and environmental pollutant imaging. Successful surface immobilization of biomolecules is critical to increasing the stabilization, sensitivity, and selectivity of biomolecules used in bioassay systems. Nanofibers are good candidates for the immobilization of biomolecules owing to many advantages such as morphology and pore size. In this study, montmorillonite (MMT) clay is modified with poly(amidoamine) (PAMAM) generation 3 (PAMAMG3) and added to polystyrene (PS) solutions, following which PS/MMT-PAMAMG3 nanofibers are obtained using the electrospinning method. The nanofibers are obtained by testing PS% (wt%) and MMT-PAMAMG3% (wt%) ratios and characterized with scanning electron microscopy. Antiserum amyloid A antibody (Anti-SAA) is then conjugated to the nanofibers on the electrode surface via covalent bonds using a zero-length cross linker. Finally, the obtained selective surface is used for electrochemical determination of serum amyloid A (SAA) levels. The linear range of PS/MMT-PAMAM/Anti-SAA is between 1 and 200 ng/mL SAA, and the detection limit is 0.57 ng/mL SAA. The applicability of PS/MMT-PAMAMG3/Anti-SAA is investigated by taking measurements in synthetic saliva and serum both containing SAA. [ABSTRACT FROM AUTHOR]

The minipig has been used as a non-rodent species in nonclinical toxicology studies, but little is known about amyloid A (AA) amyloidosis in this species. Among domestic pigs, reports of AA amyloidosis have been limited to animals with mutations in the N-terminal residue of serum AA (SAA), which is thought to be a primary etiological factor. In this study, we histologically examined 26 microminipigs aged 0.6 to 10 years and observed amyloid deposition in one 0.6-year-old and six 5-year-old or older microminipigs. The amyloid deposits were identified as AA based on mass spectrometry (MS) and immunohistochemistry (IHC). The 0.6-year-old microminipig showed severe deposition in the renal cortex and spleen, whereas 5-year-old or older animals had severe deposition in the renal medulla. MS and IHC detected serum amyloid P-component (SAP) in amyloid deposits in older animals but not in a 0.6-year-old animals. Based on the proteomic analysis and gene sequencing, amino acid mutations of SAA, previously found in domestic pigs, were not involved in the pathogenesis of AA amyloidosis in microminipigs. This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype. [ABSTRACT FROM AUTHOR]

Pre-slaughter handling, which include transportation, housing, social stress, heat, and dietary changes, is one of the main causes that produces stress in pigs. The appropriate biomarkers and objective laboratory criteria to evaluate pre-slaughter stress are lacking. Behavioral and physiological markers are commonly used for this reason, but these parameters may increase for reasons unrelated to stress. Acute phase proteins are considered to be markers of inflammation that have been proposed as indicators for farm animal stress monitoring. The major acute phase proteins in swine are haptoglobin, serum amyloid A, c-reactive protein, and pig major acute phase protein. Serum or plasma obtained from blood are the most used matrixes for the measurement of acute phase proteins, the collection of which involves an invasive collection method that is harmful and stressing. The use of saliva and meat juice instead of blood might overcome these disadvantages, since its collection is non-invasive and stress-free. For any assay measuring acute phase proteins, adequate analytical validation must be performed, as well as harmonization and standardization of analytical procedures. The aim of this paper is to emphasize the possibilities of use of acute phase proteins as biomarkers of pre-slaughter stress, as well as to provide survey of methodologic assays and fluids that are presently available to measure acute phase proteins. [ABSTRACT FROM AUTHOR]