Comparison between soluble ST2 and high-sensitivity troponin I in predicting short-term mortality for patients presenting to the Emergency Department with chest pain

Background: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. Methods: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. Results: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P35 ng/mL at ED arrival died during the 30-day follow-up. Conclusions: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value > 35 ng/mL at ED arrival showed the highest predictive power for short-term mortality

Serum Cystatin C for the diagnosis of acute Kidney Injury in Patients Admitted in the Emergency Department

BACKGROUND: Early diagnosis of acute kidney injury (AKI) at emergency department (ED) is a challenging issue. Current diagnostic criteria for AKI poorly recognize early renal dysfunction and may cause delayed diagnosis. We evaluated the use of serum cystatin C (CysC) for the early and accurate diagnosis of AKI in patients hospitalized from the ED. METHODS: In a total of 198 patients (105 males and 93 females), serum CysC, serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were calculated at 0, 6, 12, 24, 48, and 72 hours after presentation to the ED. We compared two groups according to the presence or absence of AKI. RESULTS: Serial assessment of CysC, sCr, and eGFR was not a strong, reliable tool to distinguish AKI from non-AKI. CysC > 1.44 mg/L at admission, both alone (Odds Ratio = 5.04; 95%CI 2.20-11.52; P < 0.0002) and in combination with sCr and eGFR (Odds Ratio = 5.71; 95%CI 1.86-17.55; P < 0.002), was a strong predictor for the risk of AKI. CONCLUSIONS: Serial assessment of CysC is not superior to sCr and eGFR in distinguishing AKI from non-AKI. Admission CysC, both alone and in combination with sCr and eGFR, could be considered a powerful tool for the prediction of AKI in ED patients

Proenkephalin, neutrophil gelatinase-associated lipocalin, and estimated glomerular filtration rates in patients with sepsis

Background: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (EGFR) in septic patients. Methods: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPICr, CDK-EPICysC, and CKD-EPICr-CysC. The PENK, NGAL, and EGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. Results: The PENK, NGAL, and EGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different EGFR equations, PENK showed constant and significant associations with all EGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. Conclusions: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis

Soluble ST2 levels and left ventricular structure and function in patients with metabolic syndrome

Background: A biomarker that is of great interest in relation to adverse cardiovascular events is soluble ST2 (sST2), a member of the interleukin family. Considering that metabolic syndrome (MetS) is accompanied by a proinflammatory state, we aimed to assess the relationship between sST2 and left ventricular (LV) structure and function in patients with MetS. Methods: A multicentric, cross-sectional study was conducted on180 MetS subjects with normal LV ejection fraction as determined by echocardiography. LV hypertrophy (LVH) was defined as an LV mass index greater than the gender-specific upper limit of normal as determined by echocardiography. LV diastolic dysfunction (DD) was assessed by pulse-wave and tissue Doppler imaging. sST2 was measured by using a quantitative monoclonal ELISA assay. Results: LV mass index (β=0.337, P<0 .001, linear regression) was independently associated with sST2 concentrations. Increased sST2 was associated with an increased likelihood of LVH [Exp (B)=2.20, P=0.048, logistic regression] and increased systolic blood pressure [Exp (B)=1.02, P=0.05, logistic regression]. Comparing mean sST2 concentrations (adjusted for age, body mass index, gender) between different LV remodeling patterns, we found the greatest sST2 level in the group with concentric hypertrophy. There were no differences in sST2 concentration between groups with and without LV DD. Conclusions: Increased sST2 concentration in patients with MetS was associated with a greater likelihood of exhibiting LVH. Our results suggest that inflammation could be one of the principal triggering mechanisms for LV remodeling in MetS

A versatile and user-friendly approach for the analysis of proteins in ancient and historical objects

Identification and characterization of ancient proteins still require technical developments towards non-invasiveness, sensitivity, versatility and ease of use of the analyses. We report that the enzyme functionalized films, described in Cicatiello et al. (2018), can be used efficiently on the surface of different objects ranging from fixative-coated paper to canvas to the coating on an albumen photograph, as well as the much harder surfaces of ivory objects and the proteinaceous binders in the decoration of a wooden Egyptian coffin. The mixture of digested peptides that are efficiently captured on the functionalized surface are also amenable to LC-MS/MS analysis, which is necessary to confidently identify chemical modifications induced upon degradation, in order to characterize the conservation state of proteins. Moreover, in a two-step procedure, we have combined the trypsin functionalized film with a PNGaseF functionalized film, which adds a deglycosylation pretreatment allowing improved detection of glycosylated proteins. SIGNIFICANCE: User friendly trypsin functionalized films were implemented to expand their potential as versatile, modular tools that can be widely exploited in the world of diagnosis of cultural heritage objects, ancient proteins, and palaeoproteomics: a procedure that could be carried out by conservators or archaeologists first on-site and later analysed with standard MS techniques

Greatwall kinase: a nuclear protein required for proper chromosome condensation and mitotic progression in Drosophila

Mutations in the Drosophila gene greatwall cause improper chromosome condensation and delay cell cycle progression in larval neuroblasts. Chromosomes are highly undercondensed, particularly in the euchromatin, but nevertheless contain phosphorylated histone H3, condensin, and topoisomerase II. Cells take much longer to transit the period of chromosome condensation from late G2 through nuclear envelope breakdown. Mutant cells are also subsequently delayed at metaphase, due to spindle checkpoint activity. These mutant phenotypes are not caused by spindle aberrations, by global defects in chromosome replication, or by activation of a caffeine-sensitive checkpoint. The Greatwall proteins in insects and vertebrates are located in the nucleus and belong to the AGC family of serine/threonine protein kinases; the kinase domain of Greatwall is interrupted by a long stretch of unrelated amino acids

Moonlighting in Mitosis: Analysis of the Mitotic Functions of Transcription and Splicing Factors

Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions

Moonlighting in mitosis:Analysis of the mitotic functions of transcription and splicing factors

Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions

Identification of Drosophila Mitotic Genes by Combining Co-Expression Analysis and RNA Interference

RNAi screens have, to date, identified many genes required for mitotic divisions of Drosophila tissue culture cells. However, the inventory of such genes remains incomplete. We have combined the powers of bioinformatics and RNAi technology to detect novel mitotic genes. We found that Drosophila genes involved in mitosis tend to be transcriptionally co-expressed. We thus constructed a co-expression–based list of 1,000 genes that are highly enriched in mitotic functions, and we performed RNAi for each of these genes. By limiting the number of genes to be examined, we were able to perform a very detailed phenotypic analysis of RNAi cells. We examined dsRNA-treated cells for possible abnormalities in both chromosome structure and spindle organization. This analysis allowed the identification of 142 mitotic genes, which were subdivided into 18 phenoclusters. Seventy of these genes have not previously been associated with mitotic defects; 30 of them are required for spindle assembly and/or chromosome segregation, and 40 are required to prevent spontaneous chromosome breakage. We note that the latter type of genes has never been detected in previous RNAi screens in any system. Finally, we found that RNAi against genes encoding kinetochore components or highly conserved splicing factors results in identical defects in chromosome segregation, highlighting an unanticipated role of splicing factors in centromere function. These findings indicate that our co-expression–based method for the detection of mitotic functions works remarkably well. We can foresee that elaboration of co-expression lists using genes in the same phenocluster will provide many candidate genes for small-scale RNAi screens aimed at completing the inventory of mitotic proteins