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Background Traditional cardiovascular risk factors and a large number of biomarkers are well known in their association with the diagnosis and prognosis of coronary artery disease (CAD). Cyclophilin C (CypC) is a subfamily of immunophilins that modulates macrophage activation and redox homeostasis. Purpose This study is aimed at investigating the changes in serum CypC levels and their relationship with cardiovascular events at 12 months of follow-up in CAD patients. Methods The study included a total of 125 subjects (40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers). We analyzed plasma CypC levels from baseline to 6 and 12 months for a better understanding of its behaviour in atherosclerosis. Results Serum CypC levels were shown to be gradually increased in CAD patients [(30.63 pg/mL ± 3.77 at baseline, 38.70 pg/mL ± 6.41 at 6 months (p=0.25) and 47.27 pg/mL ± 5.65 at 12 months (p=0.007)]. In addition, serum CypC levels during the follow-up were a significant predictor of CAD (c- statistic 0.76 at 6 months and 0.89 at 12 months; p2.3 mg/L plus NT-proBNP >300pg/mL together were significant predictors of cardiovascular events during the follow-up in CAD patients with CypC levels >17.5 pg/mL (p=0.048). Conclusions Taken together, our results suggest that serum CypC levels increase during the follow-up in CAD patients and could be a novel biomarker with a possible prognostic value in combination with hsCRP and NT-proBNP. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III. Spain

This study is aimed at investigating the changes in serum CypC levels and their relationship with cardiovascular events at 12 months of follow-up in coronary artery disease (CAD) patients.The study included a total of 125 subjects (40 patients with acute CAD, 40 patients with chronic CAD, and 45 control volunteers) and we analyzed plasma CypC levels from baseline to 6 and 12 months for a better understanding of its behavior in atherosclerosis.Serum CypC levels were shown to be gradually increased in CAD patients (30.63 pg/mL ± 3.77 at baseline, 38.70 pg/mL ± 6.41 at 6 months [p = 0.25], and 47.27 pg/mL ± 5.65 at 12 months [p = 0.007]). In addition, serum CypC levels during the follow-up were a significant predictor of CAD (c-statistic 0.76 at 6 months and 0.89 at 12 months; p0.001). Despite it, there was no significant association between CypC and cardiovascular events, but serum CypC levels tended to be higher in patients suffering cardiovascular events during the follow-up (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). In this regard, plasma levels of high-sensitivity C-reactive protein (hsCRP)2.3 mg/L plus NT-proBNP300 pg/mL together were significant predictors of cardiovascular events during the follow-up in CAD patients with CypC levels17.5 pg/mL (p = 0.048).Taken together, our results suggest that serum CypC levels increase during the follow-up in CAD patients and could be a novel biomarker with a possible prognostic value in combination with hsCRP and NT-proBNP.Este estudio tiene como objetivo investigar los cambios en los niveles séricos de CypC y su relación con eventos cardiovasculares a los 12 meses de seguimiento en pacientes con EAC.El estudio incluyó un total de 125 sujetos (40 pacientes con EAC aguda, 40 pacientes con EAC crónica y 45 voluntarios de control) y se analizaron los niveles ­plasmáticos de CypC desde el inicio hasta los 6 y 12 meses para comprender mejor su comportamiento en la aterosclerosis.Se demostró que los niveles séricos de CypC aumentaron gradualmente en pacientes con CAD [(30.63 pg/ml ± 3.77 al inicio del estudio, 38.70 pg/ml ± 6.41 a los 6 meses (p = 0.25) y 47.27 pg/ml ± 5.65 a los 12 meses (p = 0,007)]. Además, los niveles séricos de CypC durante el seguimiento fueron un predictor significativo de EAC (estadístico c 0.76 a los 6 meses y 0.89 a los 12 meses; p0.001). A pesar de ello, no hubo asociación significativa entre CypC y eventos cardiovasculares, pero los niveles séricos de CypC tendieron a ser más altos en los pacientes que sufrieron eventos cardiovasculares durante el seguimiento (29.02 pg/mL ± 6.39 vs. 79.96 pg/mL ± 22.18; p = 0.029). En este sentido, los niveles plasmáticos de hsCRP2.3 mg/L más NT-proBNP300 pg/ml juntos fueron predictores significativos de eventos cardiovasculares durante el seguimiento en pacientes con EAC con niveles de CypC17.5 pg/ml (p = 0.048).Tomados en conjunto, nuestros resultados sugieren que los niveles séricos de CypC aumentan durante el seguimiento en pacientes con EAC y podría ser un nuevo biomarcador con un posible valor pronóstico en combinación con hsCRP y NT-proBNP.

© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Peptidyl-prolyl cis-trans isomerase C (Ppic) is expressed in several bone marrow (BM) hematopoietic progenitors and in T-cell precursors. Since the expression profile of Ppic in the hematoimmune system was suggestive that it could play a role in hematopoiesis and/or T lymphocyte differentiation, we sought to test that hypothesis in vivo. Specifically, we generated a Ppic-deficient mouse model by targeting the endogenous locus by CRISPR/Cas9 and tested the requirement of Ppic in hematopoiesis. Several immune cell lineages covering BM progenitors, lymphocyte precursors, as well as mature cells at the periphery were analyzed. While most lineages were unaffected, invariant NKT (iNKT) cells were reduced in percentage and absolute cell numbers in the Ppic-deficient thymus. This affected the most mature stages in the thymus, S2 and S3, and the phenotype was maintained at the periphery. Additionally, immature transitional T1 and T2 B lymphocytes were increased in the Ppic-deficient spleen, but the phenotype was lost in mature B lymphocytes. In sum, our data show that Ppic is dispensable for myeloid cells, platelets, erythrocytes, αβ, and γδ T lymphocytes in vivo in the steady state, while being involved in B- and iNKT cell differentiation., This work was supported by the Instituto Gulbenkian de Ciência (IGC) of the Calouste Gulbenkian Foundation, and the Portuguese National Research Council (Fundação para a Ciência e Tecnologia [FCT]) Grant PTDC/BIA-BID/30925/2017 to VCM, that also supports the salary of RSP. VCM is supported by an individual contract awarded by FCT (CEECIND/03106/2018). CVR is a PhD student of the IGC Integrative Biology and Biomedicine (IBB) PhD Program and supported by an individual FCT PhD Fellowship ref. PD/BD/139190/2018. This work had the support of the research infrastructures Congento LISBOA-01-0145-FEDER-022170 and PPBI-POCI-01-0145-FEDER-022122, both cofinanced by FCT and Lisboa2020, under PORTUGAL2020 agreement (European Regional Development Fund).

Hepatic stellate cell activation, characterized by hyperproliferation and increased release of collagens, is a critical event during the initiation and development of hepatic fibrosis. The deregulated genes among different expression profiles based on online datasets were analyzed, attempting to identify novel potential biomarkers and treatment targets for hepatic fibrosis. The abnormal upregulation of mouse peptidylprolyl isomerase C (Ppic) within the CCl

Salmonella is a well-known food-borne pathogen causing disease in humans and animals worldwide. Peptidyl-prolyl isomerases (PPIases) catalyse the cis–trans isomerisation of prolyl bound, which is a slow and rate-limiting step of protein folding. Here, we present the biochemical and molecular characterisation of a novel multi-domain parvulin-type, PPIases-C from the pathogenic bacteria Salmonella Typhimurium, annotated as rPpiC. The recombinant plasmid PpiC_pET28c was used for protein induction using 1.5 mM concentration of isopropyl-β-D-thiogalactopyranoside at 30 °C. Subsequently, the protein was identified by using the LC–MS technique showing high match score and sequence coverage with available PPIases-C proteins database. Using the succinyl-ala-phe-pro-phe-p nitroanilide as a substrate, Vmax of the enzyme was found to be 0.8187 ± 0.1352 µmoles/min and Km = 1.6014 ± 0.8449 µM, respectively. With this, we conclude that rPpiC protein is an active form of protein from Salmonella Typhimurium and plays an important role in protein folding.

Human cytomegalovirus uses a variety of mechanisms to evade immune recognition through major histocompatibility complex class I molecules. One mechanism mediated by the immunoevasin protein US2 causes rapid disposal of newly synthesized class I molecules by the endoplasmic reticulum-associated degradation pathway. Although several components of this degradation pathway have been identified, there are still questions concerning how US2 targets class I molecules for degradation. In this study we identify cyclophilin C, a peptidyl prolyl isomerase of the endoplasmic reticulum, as a component of US2-mediated immune evasion. Cyclophilin C could be co-isolated with US2 and with the class I molecule HLA-A2. Furthermore, it was required at a particular expression level since depletion or overexpression of cyclophilin C impaired the degradation of class I molecules. To better characterize the involvement of cyclophilin C in class I degradation, we used LC-MS/MS to detect US2-interacting proteins that were influenced by cyclophilin C expression levels. We identified malectin, PDIA6, and TMEM33 as proteins that increased in association with US2 upon cyclophilin C knockdown. In subsequent validation all were shown to play a functional role in US2 degradation of class I molecules. This was specific to US2 rather than general ER-associated degradation since depletion of these proteins did not impede the degradation of a misfolded substrate, the null Hong Kong variant of α1-antitrypsin.

Current treatment methods for patients diagnosed with gliomas have shown limited success. This is partly due to the lack of prognostic genes available to accurately predict disease outcomes. The aim of this study was to investigate novel prognostic genes based on the molecular profile of tumor samples and their correlation with clinical parameters. In the current study, microarray data (GSE4412 and GSE7696) downloaded from Gene Expression Omnibus were used to identify differentially expressed prognostic genes (DEPGs) by significant analysis of microarray (SAM) between long-term survivors (>2 years) and short-term survivors (≤2 years). DEPGs generated from these two datasets were intersected to obtain a list of common DEPGs. The expression of a subset of common DEPGs was then independently validated by real-time reverse transcription quantitative PCR (qPCR). Survival value of the common DEPGs was validated using known survival data from the GSE4412 and TCGA dataset. After intersecting DEPGs generated from the above two datasets, three genes were identified which may potentially be used to determine glioma patient prognosis. Independent validation with glioma patients tissue (n = 70) and normal brain tissue (n = 19) found PPIC, EMP3 and CHI3L1 were up-regulated in glioma tissue. Survival value validation showed that the three genes correlated with patient survival by Kaplan-Meir analysis, including grades, age and therapy.