AZU1 Research Articles

Can We Improve Mortality Prediction in Patients with Sepsis in the Emergency Department?

Background and Objectives: Sepsis represents a global health challenge and requires advanced diagnostic and prognostic approaches due to its elevated rate of morbidity and fatality. Our study aimed to assess the value of a novel set of six biomarkers combined with severity scores in predicting 28 day mortality among patients presenting with sepsis in the Emergency Department (ED). Materials and Methods: This single-center, observational, prospective cohort included sixty-seven consecutive patients with septic shock and sepsis enrolled from November 2020 to December 2022, categorized into survival and non-survival groups based on outcomes. The following were assessed: procalcitonin (PCT), soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1), the soluble form of the urokinase plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and azurocidin 1 (AZU1), alongside clinical scores such as the Quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II and III (SAPS II/III), the National Early Warning Score (NEWS), Mortality in Emergency Department Sepsis (MEDS), the Charlson Comorbidity Index (CCI), and the Glasgow Coma Scale (GCS). The ability of each biomarker and clinical score and their combinations to predict 28 day mortality were evaluated. Results: The overall mortality was 49.25%. Mechanical ventilation was associated with a higher mortality rate. The levels of IL-6 were significantly higher in the non-survival group and had higher AUC values compared to the other biomarkers. The GCS, SOFA, APACHEII, and SAPS II/III showed superior predictive ability. Combining IL-6 with suPAR, AZU1, and clinical scores SOFA, APACHE II, and SAPS II enhanced prediction accuracy compared with individual biomarkers. Conclusion: In our study, IL-6 and SAPS II/III were the most accurate predictors of 28 day mortality for sepsis patients in the ED.

AZU1: a new promising marker for infection in orthopedic and trauma patients?

Early and reliable detection of infection is vital for successful treatment. Serum markers such as C-reactive protein (CRP) and procalcitonin (PCT) are known to increase with a time lag. Azurocidin 1 (AZU1) has emerged as a promising marker for septic patients, but its diagnostic value in orthopedic and trauma patients remains unexplored. Between July 2020 and August 2023, all patients necessitating inpatient treatment for periprosthetic joint infection (PJI), peri-implant infection (II), soft tissue infection, chronic osteomyelitis, septic arthrodesis, bone non-union with and without infection were enrolled. Patients undergoing elective total joint arthroplasty (TJA) served as the control group. Blood samples were collected and analyzed for CRP, white blood cell count (WBC), PCT, and AZU1. Based on the inclusion and exclusion criteria 222 patients were included in the study (trauma = 38, soft tissue infection = 75, TJA = 33, PJI/II = 39, others = 37). While sensitivity and specificity were comparably high for AZU1 (0.734/0.833), CRP and PCT had higher specificity (0.542/1 and 0.431/1, respectively), and WBC a slightly higher sensitivity (0.814/0.455) for septic conditions. Taken together, the area under the curve (AUC) showed the highest accuracy for AZU1 (0.790), followed by CRP (0.776), WBC (0.641), and PCT (0.656). The Youden-Index was 0.57 for AZU1, 0.54 for CRP, 0.27 for WBC, and 0.43 for PCT. Elevated AZU1 levels effectively distinguished patients with a healthy condition from those suffering from infection. However, there is evidence suggesting that trauma may influence the release of AZU1. Additional research is needed to validate the diagnostic value of this new biomarker and further explore its potential clinical applications.

Azurocidin 1 inhibits the aberrant proliferation of triple‑negative breast cancer through the regulation of pyroptosis.

Azurocidin 1 (AZU1) is a heparin‑binding protein which has been reported to be aberrantly expressed in various tumors, but its definite role in breast cancer (BC) has not been clarified. The aim of the present study was to explore the associations between AZU1 and BC. In the present study, bioinformatics and western blot analyses were applied to detect the expression level of AZU1 in BC tissues. The effect of AZU1 on cell proliferation and apoptosis was analyzed using Cell Counting Kit‑8 assay, colony formation assay and flow cytometry. Based on bioinformatics analysis, AZU1 exhibited low expression in tissues and was negatively associated with the survival rate of patients with triple‑negative BC (TNBC). Exogenous AZU1 stimuli significantly inhibited the proliferation and colony formation of TNBC cell lines. Furthermore, the data of flow cytometry revealed that exogenous AZU1 stimuli enhanced apoptosis in MDA‑231 and BT‑549 cells. As pyroptosis is a new type of cell death, the effects AZU1 played on the expression of gasdermin D (GSDMD), a specific biomarker of pyroptosis, were also investigated. The findings of the present study revealed that GSDMD, as well as its upstream regulators [NF‑κB, NLR family pyrin domain containing3 (NLRP3) and caspase‑1], were significantly increased in TNBC cell lines when treated with exogenous AZU1, indicating that AZU1 contributed to the inhibition of pyroptosis of TNBC cell lines through the NF‑κB/NLRP3/caspase‑1 axis. Collectively, it was revealed for the first time, that AZU1 exposure promoted pyroptosis through the modulation of the pNF‑κB/NLRP3/caspase‑1/GSDMD axis in TNBC invitro. The findings of the present study unveiled a novel mechanism of AZU1‑induced pyroptosis in TNBC, which may aid in developing new strategies for therapeutic interventions in TNBC. breast cancer is the most commone form of cancer in women and is second only to lung cancer in terms of cancer‑related mortality.

Is there a Correlation between Monocyte Chemoattractant Protein-1 with Autotaxin, Azurocidin-1, Apolipoprotein C-III and Elastase-2 in Male Iraqi Acute Myocardial Infraction Patients?

Acute Myocardial infarction (AMI) is one of the important reasons of loss of life and bodily incapacity global prompt via cardiovascular diseases (CVD). AMI stimulates the innate immune system that is required to employee leukocytes to remove necrotic cells and recruit myocardial healing. To evaluate serum concentrations of Monocyte Chemoattractant Protein-1 (MCP-1), Autotaxin (ATX), Azurocidin-1 (AZU-1), Apolipoprotein C-III (APOC3) and Elastase-2 (ELA-2) in male Iraqi AMI patients and healthy controls (HCs), and explain the association of MCP-1with ATX, AZU-1, APOC3 and ELA-2 in male Iraqi AMI patients, also explore the best parameter which can use to differentiate between AMI patients. This case-control study included 84 men aged 40–68 years. Waist circumference (WC), hip circumference (HC), thoracic circumference (TC), neck circumference (NC), height, weight, age, and further covariates were obtained via an inquiry form. They were separated into two equivalent groups: the patients group and the healthy group, serum concentrations of MCP-1, ATX, AZU-1, APOC3 and ELA-2 were estimated via ELISA. Serum of MCP-1, ATX, AZU-1, APOC3 and ELA-2 concentrations were importantly greater in patients with AMI than in HCs (p< 0.001). MCP-1 concentrations were importantly linked with ATX, AZU-1, APOC3 and ELA-2 in AMI cases (p< 0.001). The greater value of MPC-1 association was with ELA-2 (r=0.592). MCP-1 exhibited the maximum value for área under curve (AUC=1) in comparison to other studied biomarkers. The present data explained the role of MCP-1, ATX, AZU-1, APOC3 and ELA-2 in AMI disease; we found they have central functions in this disease, mainly obese patients. Attention must be taken to avoid confusion among risk markers and risk factors. Great serum concentrations of MCP-1 offered important correlations between risk markers and risk factors of AMI disease.

A quantitative proteomics study on olfactomedin 4 in the development of gastric cancer.

Gastric cancer (GC) is now one of the most common malignancies with a relatively high incidence and high mortality rate. The prognosis is closely related to the degree of tumor metastasis. The mechanism of metastasis is still unclear. Proteomics analysis is a powerful tool to study and evaluate protein expression in tumor tissues. In the present study, we collected 15 gastric cancer and adjacent normal gastric tissues and used the isobaric tags for relative and absolute quantitation (iTRAQ) method to identify differentially expressed proteins. A total of 134 proteins were differentially expressed between the cancerous and non-cancerous samples. Azurocidin 1 (AZU1), CPVL, olfactomedin 4 (OLFM4) and Villin 1 (VIL1) were upregulated and confirmed by western blot analysis, real-time quantitative PCR and immunohistochemical analyses. These results were in accordance with iTRAQ. Furthermore, silencing the OLFM4 expression suppressed the migration, invasion and proliferation of the GC cells in vitro. The present study represents a successful application of the iTRAQ method in analyzing the expression levels of thousands of proteins. Overexpression of OLFM4 in gastric cancer may induce the development of gastric cancer. Overall, suppression of OLFM4 expression may be a promising strategy in the development of novel cancer therapeutic drugs.

Clinical significance and identification analysis of differentially expressed proteins (TM9SF1 and AZU1) in the wall of ruptured intracranial aneurysms

Objective To further identify the differentially expressed proteins (TM9SF1and AZU1) screened in our previous study in order to explore their roles in formation and rupture of intracranial aneurysms (IAs).Methods Twenty ruptured IAs underwent microsurgical clipping.During the procedure,a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for TM9SF1 and AZU1.A segment of the superficial temporal artery from the same patient was also removed and used as control group.Western blot analysis was performed to confirm the expression profile of two proteins.Results All 20 aneurysm tissues stained positive for TM9SF1 and AZU1,while negative or poor positive in STA tissues.Their expression was more abundant (P ＜ 0.05) in ruptured IA tissues than STA tissues,based on a semiquantitative grading.According to western blot analysis,relative expression of TM9SF1 and AZU1 was 4.2 and 5.6 respectively in IA tissues compared with STA tissues.Conclusions TM9SF1/AZU1 are more abundantly expressed in the wall of human ruptured IAs than in STA tissues.We speculate that the proteins may participate in formation and rupture of IAs. Key words: Intracranial aneurysm; Rupture; Immunohistochemistry; Western blot

Quantitative proteomic analysis of the intracranial aneurysm wall using iTRAQ labeling coupled with 2D LC-MS/MS

Objective To screen the differentially expressed proteins of the intracranial aneurysm wall and provide some clues to the study of molecular mechanisms of its formation and rupture.Methods Aneurysm wall samples were intraoperatively collected from 14 patients underwent microneurosurgical clipping and the matched superficial temporal artery tissues from the patients with head injury were used as the normal control.All vascular tissues in the same group were mixed up by each equal weight(5mg).The differentially expressed proteins were identified using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry(2D LC-MS/MS).Results A total of 915 proteins were identified,255 of which differed more than two-fold in ruptured aneurysm wall tissues compared with the control group,including 102 up-regulated proteins and 153 down-regulated ones.In the up-regulated proteins,there were a number of proteins associated with biological process including immune response,inflammation response,cell motion,cell adhesion,cell apoptosis and autophagy while cell skeleton junction,cell component morphology formation,signaling transduction and protein transport in the down-regulated ones.Transmembrane 9 superfamily member 1 (TM9SF1,8.0 fold) and Azurocidin (AZU1,8.0 fold) were markedly increased among the up-regulated proteins.Sorbin and SH3 domain-containing protein 2 (SORBS2,12.1 fold) was markedly decreased among the down-regulated proteins.Conclusions The results suggest that a number of proteins expressed differently in ruptured aneurysm wall tissues.Major proteins such as TM9SF1,AZU1,and SORBS2,may participate in the molecular mechanisms of aneurysm rupture.This knowledge would be important value for elucidating molecular mechanisms of aneurysm rupture and formation and insight for novel therapeutic strategies to prevent rupture. Key words: Intracranial aneurysm ; Proteomic analysis ; Itraq ; 2D LC-MS/MS

Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes

BackgroundGene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment.FindingsBy using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection.ConclusionStudy of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.

The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps

Pentraxin 3 (PTX3), a long pentraxin subfamily member in the pentraxin family, plays an important role in innate immunity as a soluble pattern recognition receptor. Plasma PTX3 is elevated in sepsis (∼200 ng/ml) and correlates with mortality. The roles of PTX3 in sepsis, however, are not well understood. To investigate the ligands of PTX3 in sepsis, we performed a targeted proteomic study of circulating PTX3 complexes using magnetic bead-based immunopurification and shotgun proteomics for label-free relative quantitation via spectral counting. From septic patient fluids, we successfully identified 104 candidate proteins, including the known PTX3-interacting proteins involved in complement activation, pathogen opsonization, inflammation regulation, and extracellular matrix deposition. Notably, the proteomic profile additionally showed that PTX3 formed a complex with some of the components of neutrophil extracellular traps. Subsequent biochemical analyses revealed a direct interaction of bactericidal proteins azurocidin 1 (AZU1) and myeloperoxidase with PTX3. AZU1 exhibited high affinity binding (KD = 22 ± 7.6 nm) to full-length PTX3 in a calcium ion-dependent manner and bound specifically to an oligomer of the PTX3 N-terminal domain. Immunohistochemistry with a specific monoclonal antibody generated against AZU1 revealed a partial co-localization of AZU1 with PTX3 in neutrophil extracellular traps. The association of circulating PTX3 with components of the neutrophil extracellular traps in sepsis suggests a role for PTX3 in host defense and as a potential diagnostic target.