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Summary: The inflammatory response to a truly closed castration procedure in 51 horses using an inguinal approach was quantified by serum amyloid A (SAA) measurements to be on average 94 mg/L on day three after surgery. The average SAA value after field castrations, using a scrotal approach, was reported by four different investigations to be between 480 and 708 mg/L on day three post‐operatively. The discrepancy in SAA levels between these different approaches proved to be significant (p < 0.001), quantifying a substantially lower inflammatory response of the closed inguinal technique over regular field castrations using a scrotal approach. [ABSTRACT FROM AUTHOR]

AbstractAA amyloidosis is a prototypic example of systemic amyloidosis: it results from the prolonged overproduction of SAA protein produced in response to chronic inflammation. AA amyloidosis primarily affects the kidneys, liver, spleen, gastrointestinal tract, leading to a variety of symptoms. First, this review examines AA amyloidosis in humans, focusing on pathogenesis, clinical presentation, and diagnosis and then in animals. In fact AA amyloidosis is the only systemic amyloidosis that has been largely documented in a remarkable number of vertebrate species: mammals, birds, and fishes, especially in individuals with comorbidities, chronic stress, or held in captivity. Secondly, here, we summarise independent sets of evidence obtained on different animal species, exploring the possible transmissibility of AA amyloidosis especially in crowded or confined populations. Finally, biochemical and structural data on native SAA and on AA amyloid fibrils from human, murine, and cat ex vivo samples are discussed. The available structural data depict a complex scenario, where SAA can misfold forming highly different amyloid assemblies. This review highlights the complexity of AA amyloidosis, emphasising the need for further research into its spread in the animal kingdom, its structural aspects, and pathogenetic mechanisms to evaluate its impact on human and animal health. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is one of the most important precursor amyloid proteins discovered during the study of amyloidosis, but its underlying aggregation mechanism has not yet been well elucidated. Since SAA aggregation is a key step in the pathogenesis of AA amyloidosis, amyloid inhibitors can be used as a tool to study its pathogenesis. Previously, we reported a novel microliter-scale high-throughput screening (MSHTS) system for screening amyloid β (Aβ) aggregation inhibitors based on quantum dot (QD) fluorescence imaging technology. In this study, we report the aggregation of human SAA (hSAA) in phosphate-buffered saline, in which we successfully visualized hSAA aggregation by QD using fluorescence microscopy and confocal microscopy. Two-dimensional and three-dimensional image analyses showed that most aggregations were observed at 40 μM hSAA, which was the optimal aggregation concentration in vitro. The accuracy of this finding was verified by a Thioflavin T assay. The transmission electron microscopy results showed that QD uniformly bound to hSAA aggregation. hSAA aggregation inhibitory activity was also evaluated by rosmarinic acid (RA). The results showed that RA, which is a compound with high inhibitory activity against Aβ aggregation, also exhibited high inhibitory activity against 40 μM hSAA. These results indicate that the MSHTS system is an effective tool for visualizing hSAA aggregation and for screening highly active inhibitors. [ABSTRACT FROM AUTHOR]

Objective To measure the levels of serum human beta-defensin-1 (HBD-1), serum amyloid A (SAA), and soluble interleukin-2 receptor (SIL-2R) in patients with community-acquired pneumonia (CAP) and to analyze their significance in guiding disease severity classification. Methods From July 2021 to August 2023,85 CAP patients (the CAP group) treated at the hospital were selected and categorized into the low-risk (34 cases), the moderate-risk (41 cases), and the high-risk (10 cases) groups based on the Pneumonia Severity Index (PSI). Another 85 healthy adults were included as a control group. The levels of serum HBD-1, SAA, and sIL-2R in the CAP group and the control group were compared, as well as among different PSI risk categories. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of HBD-1, SAA, and sIL-2R levels for CAP patients. Spearman correlation analysis was applied to assess the re- lationship between PSI scores and the levels of serum HBD-1, SAA, and sIL-2R in CAP patients. Results Levels of serum HBD-1, SAA, and sIL-2R in the CAP patients were higher than those in the control group. Among the PSI categories, levels decreased from the high-risk to low-risk groups with significant differences (P< 0.05). ROC analysis indicated that serum levels of HBD-1 (AUC = 0.739), SAA (AUC = 0.773), and sIL-2R (AUC = 0.73) had good diagnostic value for the CAP patients (P < 0.05) Spearman correlation analysis showed positive correlations between PSI scores and levels of HBD-1 [correlation coefficient (r) = 0.304 ] SAA (r = 0.498), and sIL-2R (r = 0.435) (P < 0.05) Conclusion Serum levels of HBD-1.SAA. and SIL-2R have significant guidance value in the severity classification of CAP patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Horses used for antisera production are repeatedly hyperimmunized to produce high levels of specific antibodies. This prolonged process can lead to various health issues, including amyloidosis, which involves the accumulation of amyloid proteins in organs and tissues, potentially causing organ dysfunction and failure. These horses are often retired when they no longer produce adequate antibody levels. This study aimed to evaluate the impact of prolonged antisera production on the health of retired horses by examining their blood biochemistry and serum amyloid A (SAA) levels, which are indicators of systemic inflammation and organ damage. Materials and Methods: Blood samples were collected from 12 horses for this study. Nine horses were retired antiseraproducing horses that had been discontinued for 2 years, while three healthy non-antisera-producing horses were used as controls. These twelve horses were divided into four groups based on the duration of their active period as antisera producers (never been used, 2–3 years, 4–5 years, and 6–7 years). We measured key blood biochemistry parameters and SAA levels to evaluate the health status of the horses. Results: Total protein, fibrinogen, and globulin levels were elevated, whereas other parameters remained normal. The findings indicate that despite normal SAA levels, the horses exhibited signs of ongoing health issues related to their previous use in antisera production, such as increased total plasma protein, fibrinogen, and globulin levels, as well as the presence of amyloid deposits in vital organs such as the liver and kidneys, as observed in post-mortem examinations. Conclusion: Despite normal SAA levels, retired antisera-producing horses showed elevated total protein, fibrinogen, and globulin levels, indicating ongoing health issues. [ABSTRACT FROM AUTHOR]

Simple Summary: Previous research highlights the involvement of the Serum Amyloid A (SAA) protein family in inflammation and various diseases. This study explores the role of SAA1 and SAA2 (SAA1/2) in triple-negative breast cancer using a mouse model. Syngeneic breast tumors were established in wild-type and SAA1/2-deficient (SAADKO) mice, with assessments of tumor volume, survival, inflammatory profiles, and tumor characteristics. Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model. Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&E histological staining. Results: WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis. Conclusions: We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading. [ABSTRACT FROM AUTHOR]

The widespread presence of Fusarium mycotoxins in animal feed is a global issue, not only for the health of livestock but also for ensure the safety of food as an end product. High concentrations of zearalenone (ZEN) and deoxynivalenol (DON) have been detected in the diets of Japanese Black (JB) and Holstein Friesian (HF) breeding herds. Consequently, we monitored serum biochemical parameters over a long time in both herds, focusing on anti-Müllerian hormone (AMH) levels and acute-phase inflammation. Additionally, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and progesterone levels were measured in the HF herd. The JB herd, a ZEN-dominant model with low DON contamination, demonstrated ZEN levels that exceeded the Japanese limit in the purchased total mixed rations (TMR). Conversely, the HF herd, which primary consumes DON-dominant feed with low ZEN contamination, had high DON levels in the dent corn silage. Specifically, the JB herd's TMR contained 1.79 mg/kg ZEN and 0.58 mg/kg DON, whereas the HF herd's silage had 15.3 mg/kg DON (dried sample) and 0.1 mg/kg ZEN. Enzyme-linked immunoassay were used to measure urinary ZEN-DON levels following confirmation through liquid chromatography-tandem mass spectrometry. Urinary ZEN-DON levels measured were significantly correlated (p < 0.05, r > 0.6) in both herds. In the HF herd, AMH levels increased (p = 0.01) and serum amyloid A (SAA) levels decreased (p = 0.02) when contaminated and at the end of the monitoring period. Additionally, urinary ZEN and DON levels were significantly correlated with SAA levels (ZEN: p = 0.00, r = 0.46; DON: p = 0.03, r = 0.33), with an increase in ZEN and DON levels resulting in higher SAA levels. The JB herd showed no significant differences. Additionally, in the HF herd, 8-OHdG/Cre levels increased significantly during major contamination periods (p < 0.05). Clinical data from the HF herd indicated an increase in mastitis cases and treatment rates during periods of major contamination. Abortion rates in the HF herd decreased from 22.9% (before monitoring) to 8.9% (during the high contamination period) and finally to 1% (at the end of the monitoring period), with corresponding increases in progesterone levels. ZEN-DON contamination adversely affects breeding cattle's productivity, reproductive performance, and health. Therefore, monitoring urinary ZEN-DON is valuable for detecting contaminants and ensuring the safety of food products. [ABSTRACT FROM AUTHOR]

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]

OBJECTIVE Comparing the utility of the anti-human serum amyloid A (SAA)-specific monoclonal and polyclonal antibodies assays (LZ-SAA) with the pure monoclonal anti-human antibody assays (VET-SAA) during clinical practice in primary care hospital populations by measuring SAA measurement in healthy and diseased domestic cats. ANIMALS 52 healthy and 185 diseased client-owned cats. METHODS SAA concentration was measured using different LZ-SAA and VET-SAA measurements for healthy and various diseased cats. Sensitivity, specificity, and accuracy were calculated for each disease. RESULTS VET-SAA has higher sensitivity than LZ-SAA for the most common diseases presenting to primary care veterinary hospitals, including chronic kidney disease, tumors, and gingivostomatitis. Our results reveal the capability of detecting low SAA concentrations in healthy and diseased cats using VET-SAA in contrast to LZ-SAA, which found elevations of SAA concentrations only in diseased cats. CLINICAL RELEVANCE Our findings indicate that switching to the new VET-SAA instead of the conventional LZ-SAA will likely enhance the diagnostic performance in primary care veterinary hospitals. [ABSTRACT FROM AUTHOR]

• CRP and SAA are good biomarkers to discriminate crises in FMF and USAID patients. • Serum calprotectin is not a suitable biomarker to discriminate crises in SAID. • Contrary to SAA, CRP diagnostic performances were not affected by the BMI. • CRP is a suitable, not expensive and easily available biomarker to monitor SAID. With their broad presentations and no global biomarker to discriminate crises and attack-free periods, Systemic Auto-Inflammatory Diseases (SAID) are difficult to manage. This study assessed Serum Amyloid A (SAA), C-reactive protein (CRP) and serum calprotectin as potential biomarkers to monitor patients with SAID. SAA (already studied in Familial Mediterranean Fever (FMF)), CRP and serum calprotectin were measured on SAID adult patients from Juvenile Inflammatory Rheumatism (JIR) cohort during their follow-up visits between 2020 and 2022. Crises and attack-free periods were clinically determined. 96 measures, mainly from FMF (43 %) and Unclassified SAID (USAID) (37 %) patients were included. Using ROC curves, a threshold with sensitivity and specificity of/over 75 % was determined for SAA (9 mg/L) and CRP (9 mg/L) but not for serum calprotectin, not investigated further. With this threshold, the results were similar in FMF and USAID patients' subgroups. SAA and CRP showed a positive correlation with crises and attack-free periods in SAID patients (r = 0.4796, p < 0.001 and r = 0.5525, p < 0.001, respectively) as in FMF and USAID patients, with no significant difference between both markers in diagnosis value and ROC curves Area Under Curve (AUC) (p = 0.32). Only the CRP results were not influenced by obesity. SAA and CRP can discriminate crisis and attack-free periods in our cohort of SAID patients mainly composed of FMF and USAID patients. However, only CRP can be used regardless of body mass index. It is the first report of common biomarkers for all SAID, including USAID patients, with CRP widely accessible in routine worldwide. [ABSTRACT FROM AUTHOR]

Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA. Methods: A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses. Results: A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001). Conclusion: The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population. [ABSTRACT FROM AUTHOR]

Background and Aim: Horses used for antisera production are repeatedly hyperimmunized to produce high levels of specific antibodies. This prolonged process can lead to various health issues, including amyloidosis, which involves the accumulation of amyloid proteins in organs and tissues, potentially causing organ dysfunction and failure. These horses are often retired when they no longer produce adequate antibody levels. This study aimed to evaluate the impact of prolonged antisera production on the health of retired horses by examining their blood biochemistry and serum amyloid A (SAA) levels, which are indicators of systemic inflammation and organ damage. Materials and Methods: Blood samples were collected from 12 horses for this study. Nine horses were retired antisera-producing horses that had been discontinued for 2 years, while three healthy non-antisera-producing horses were used as controls. These twelve horses were divided into four groups based on the duration of their active period as antisera producers (never been used, 2–3 years, 4–5 years, and 6–7 years). We measured key blood biochemistry parameters and SAA levels to evaluate the health status of the horses. Results: Total protein, fibrinogen, and globulin levels were elevated, whereas other parameters remained normal. The findings indicate that despite normal SAA levels, the horses exhibited signs of ongoing health issues related to their previous use in antisera production, such as increased total plasma protein, fibrinogen, and globulin levels, as well as the presence of amyloid deposits in vital organs such as the liver and kidneys, as observed in post-mortem examinations. Conclusion: Despite normal SAA levels, retired antisera-producing horses showed elevated total protein, fibrinogen, and globulin levels, indicating ongoing health issues.

Community-acquired pneumonia (CAP) poses a significant global health threat, particularly affecting vulnerable populations. Biomarkers and scoring systems play a crucial role in diagnosing, assessing severity, and guiding treatment decisions for CAP patients. Biomarkers like C reactive protein, procalcitonin, and the neutrophil-to-lymphocyte ratio aid in diagnosis and severity assessment, while scoring systems such as CURB-65 and Pneumonia Severity Index classify patients into risk categories. Emerging biomarkers (uremia, elevated respiratory rate, hypotension, and age ≥ 65) like serum amyloid A and S100 proteins show promise in predicting disease severity and prognosis. However, further research is needed to determine their precise roles and clinical utility in CAP management.

Abstract 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

Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices. 83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis. In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96). FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy. [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]

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]

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]

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]

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]

In clinical practice, the study of acute-phase proteins (APP), whose levels either increase (positive APP) or decrease (negative APP) in the bloodstream during inflammation, infection, tissue damage, neoplastic growth, and specific immunological diseases in the body, is increasingly utilized. The prevailing opinion is that each animal species has its own 'major' APP, which should be considered as a diagnostic marker. In cats, the positive APP that plays a major role in the diagnostic approach in practice is feline serum amyloid A (fSAA). It serves as a sensitive marker of systemic inflammation and infection in cats. It shows an early and rapid increase in the blood, often preceding the appearance of clinical symptoms such as fever and an increased leukocyte count. The article discusses how fSAA levels can help identify and differentiate various diseases, including Infectious, inflammatory, neoplastic, and in which conditions its diagnostic value is higher than others. It also examines the prognostic value of fSAA in assessing disease severity and monitoring treatment efficacy. Technological advances in fSAA measurement instrumentation and methods facilitate its integration into routine clinical practice, improving feline health management. [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]

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]

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]

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]

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]

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]

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]

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]

Objective To investigate the expression levels of small dense low-density lipoprotein cholesterol (sdLDLC), serum amyloid A (SAA), and platelet-activating factor (PAF) in acute coronary syndrome (ACS) and their relationship with vulnerable plaques. Methods A total of 136 patients with coronary heart disease were divided into stable angina pectoris (SAP) group (n=45) and ACS group (n=91) . Based on plaque stability, they were further divided into stable plaque group (n=53) and vulnerable plaque group (n=83) . Differences in sdLDLC, SAA, PAF levels, and plaque characteristics were measured. Results Compared with the SAP group, the ACS group had a higher proportion of male gender, smoking history, levels of white blood cell (WBC), triglyceride (TG), uric acid, creatinine, sdLDLC, SAA, and PAF, and lower level of HDL-C (P＜0.05) . The ACS group showed significantly larger necrotic core (NC), lipid pool area (LPA), plaque lipid ratio (PLR), eccentric index (EI), remodeling index (RI), plaque burden (PB) compared to the SAP group (P＜0.05) . There were statistically significant differences in the expression levels of sdLDLC, SAA, and PAF between the stable plaque group and the vulnerable plaque group (P＜0.05) . Pearson correlation analysis showed that sdLDLC, SAA, and PAF were positively correlated with NT, LPA, PLR, EI, RI, PB (P＜0.05) . Multivariate logistic regression analysis revealed that sdLDLC, SAA, and PAF were independent predictors of vulnerable plaques (P＜0.05) .Conclusion Levels of sdLDLC, SAA, and PAF are significantly elevated in ACS patients and are closely related to vulnerable plaques. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum amyloid A(SAA), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and postoperative incision infection in children with acute suppurative appendicitis. Methods: 418 children with acute suppurative appendicitis were selected, and the incision infection was observed within 7 d after operation, patients were divided into infected group and uninfected group according to whether postoperative infection occurred. Preoperative serum SAA, NLR and PLR were compared between infected group and uninfected group. The influencing factors of postoperative incision infection were analyzed by univariate and multivariate Logistic regression models. The predictive value of preoperative serum SAA, NLR and PLR for postoperative incision infection were evaluated by receiver operating characteristic (ROC) curve. Results: 418 children with acute suppurative appendicitis, 54 had postoperative incision infection, with an infection rate of 12.92%. The preoperative serum SAA, NLR and PLR in infected group were higher than those in uninfected group(P<0.05). Postoperative incision infection was related to operation time and operation method (P<0.05). And not related to gender, age, incision length, and the average time from onset to surgery (P>0.05). Long preoperative operation time, elevated serum SAA, elevated NLR, elevated PLR, and operation method was laparotomy were risk factors for postoperative incision infection(P<0.05). The efficacy of combined detection of preoperative serum SAA, NLR and PLR in predicting postoperative incision infection was greater than that of each index alone. Conclusion: Preoperative serum SAA level, NLR and PLR are elevate in children with incision infection after acute suppurative appendicitis, the combine detection in three indicators has a high predictive efficiency for postoperative incision infection occurrence, serum SAA, NLR, PLR, operation time and operation method are the influencing factors of postoperative incision infection. [ABSTRACT FROM AUTHOR]

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]

Bovine ephemeral fever is an arthropod-borne viral disease that primarily affects cattle and causes economic losses mainly due to the sudden decrease in milk yield. We aimed to reveal the biochemical reflection of the acute phase response by detecting the changes in serum acute phase proteins in cattle naturally infected with the bovine ephemeral fever virus. The material of this study consisted of 21 Simmental dairy cows (4-6 years old) naturally infected with bovine ephemeral fever virus (infected group) and 10 clinically and serologically healthy Simmental dairy cows (control group). The prevalence of the disease in suspected cattle was 52 per 100. It was determined that in infected cows levels of serum haptoglobin, serum amyloid A (P = 0.001), and ceruloplasmin increased significantly (P = 0.05), whereas levels of albumin decreased significantly (P = 0.05). It is thought that the acute phase proteins variation pattern for bovine ephemeral fever would be beneficial both in better understanding the pathogenesis of the disease and in determining the diagnosis and prognosis correctly. [ABSTRACT FROM AUTHOR]

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]

IntroductionThe glutaraldehyde test (GAT) allows for animal-side semi-quantitative 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.MethodsFor the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and non-inflammatory 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.ResultsShortened 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

Abstract 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 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 (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 36 mg/L further increased the odds ratio to 4.423 (P 36 mg/L remained an independent risk factor for the development of severe COVID‐19 (adjusted odds ratio 3.038, P

Running Title: DDL inhibits the LPS-induced SAA3 gene expression in microglia Objective: Research on the mechanism of Dehydrocostus lactone (DDL) in microglial cells of the brain needs to be improved, despite its reported anti-inflammatory, anticancer, and anti-proliferation properties as a natural product of Eerdun Wurile The precise functions of the Serum amyloid A (SAA) genes are not yet defined. However, these genes are suggested to possess antibacterial properties and can attract monocytes and neutrophils. On the other hand, SAA genes can also induce inflammatory cytokines and metalloproteinases in smooth muscle cells and macrophages, thus promoting inflammation. This study aimed to investigate the impact of DDL on SAA3 gene expression in microglial cells stimulated by LPS. Methods: The anti-inflammatory effects of DDL were studied using LPS-stimulated murine BV2 microglia. BV2 was cultured in DMEM, and then 4µM DDL was added. Then BV2 was treated with one ng/ml LPS for 24 hours to stimulate. Results: LPS treatment increased the expression of SAA3 mRNA in BV2 microglial cells, while DDL pre-treatment inhibited LPS-induced SAA3 mRNA expression. Conclusion: Microglia cells treated with LPS display a significant reduction in the expression of SAA3 gene transcripts upon treatment with DDL.

The widespread presence of Fusarium mycotoxins in animal feed is a global issue, not only for the health of livestock but also for ensure the safety of food as an end product. High concentrations of zearalenone (ZEN) and deoxynivalenol (DON) have been detected in the diets of Japanese Black (JB) and Holstein Friesian (HF) breeding herds. Consequently, we monitored serum biochemical parameters over a long time in both herds, focusing on anti-Müllerian hormone (AMH) levels and acute-phase inflammation. Additionally, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and progesterone levels were measured in the HF herd. The JB herd, a ZEN-dominant model with low DON contamination, demonstrated ZEN levels that exceeded the Japanese limit in the purchased total mixed rations (TMR). Conversely, the HF herd, which primary consumes DON-dominant feed with low ZEN contamination, had high DON levels in the dent corn silage. Specifically, the JB herd’s TMR contained 1.79 mg/kg ZEN and 0.58 mg/kg DON, whereas the HF herd’s silage had 15.3 mg/kg DON (dried sample) and 0.1 mg/kg ZEN. Enzyme-linked immunoassay were used to measure urinary ZEN-DON levels following confirmation through liquid chromatography-tandem mass spectrometry. Urinary ZEN-DON levels measured were significantly correlated (p < 0.05, r > 0.6) in both herds. In the HF herd, AMH levels increased (p = 0.01) and serum amyloid A (SAA) levels decreased (p = 0.02) when contaminated and at the end of the monitoring period. Additionally, urinary ZEN and DON levels were significantly correlated with SAA levels (ZEN: p = 0.00, r = 0.46; DON: p = 0.03, r = 0.33), with an increase in ZEN and DON levels resulting in higher SAA levels. The JB herd showed no significant differences. Additionally, in the HF herd, 8-OHdG/Cre levels increased significantly during major contamination periods (p < 0.05). Clinical data from the HF herd indicated an increase in mastitis cases and treatment rates during periods of major contamination. Abortion rates in the HF herd decreased from 22.9% (before monitoring) to 8.9% (during the high contamination period) and finally to 1% (at the end of the monitoring period), with corresponding increases in progesterone levels. ZEN-DON contamination adversely affects breeding cattle’s productivity, reproductive performance, and health. Therefore, monitoring urinary ZEN-DON is valuable for detecting contaminants and ensuring the safety of food products.

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.

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]