Retracted “Serum amyloid P down-regulates CCL-1 expression, and inhibits Ras/MAPK signaling and development of breast cancer”

This article previously published in Volume 17 Issue 16 of this journal in September 2017 has been retracted in line with the guidelines from the Committee on Publication Ethics (COPE,http://publicationethics.org/ resources/guidelines). Retraction: Ding S, Li H, Li X, Wang W, Du X, Dong G, Zhang P. Serum amyloid P down-regulates CCL-1 expression, and inhibits Ras/MAPK signaling and development of breast cancer. Trop J Pharm Res 2017; 16(9):2089-2095 doi: http://dx.doi.org/10.4314/tjpr.v16i9.7 To the editor: The figures in the paper were plagiarized partly from an earlier published article, Qi et al, P-selectinmediated tablet adhesion promoters tumor growth. Oncotarget 2015;30:6(9):6584–6596, and data from a master's thesis submitted by Bin Li under the supervision of Professor Lijing Wang and Professor Cuiling Qi. Sincerely, Cuiling Qi and Lijing Wang.

Dementia in the older population is associated with neocortex content of serum amyloid P component

Despite many reported associations, the direct cause of neurodegeneration responsible for cognitive loss in Alzheimer’s disease and some other common dementias is not known. The normal human plasma protein, serum amyloid P component, a constituent of all human fibrillar amyloid deposits and present on most neurofibrillary tangles, is cytotoxic for cerebral neurones in vitro and in experimental animals in vivo. The neocortical content of serum amyloid P component was immunoassayed in 157 subjects aged 65 or more with known dementia status at death, in the large scale, population-representative, brain donor cohort of the Cognitive Function and Ageing Study, which avoids the biases inherent in studies of predefined clinico-pathological groups. The serum amyloid P component values were significantly higher in individuals with dementia, independent of serum albumin content measured as a control for plasma in the cortex samples. The odds ratio for dementia at death in the high serum amyloid P component tertile was 5.24 (95% CI 1.79–15.29) and was independent of Braak tangle stages and Thal amyloid-β phases of neuropathological severity. The strong and specific association of higher brain content of serum amyloid P component with dementia, independent of neuropathology, is consistent with a pathogenetic role in dementia.

Blood fibrocytes are associated with severity and prognosis in COVID-19 pneumonia

Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during Coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/Collagen-1+cells in patients hospitalized for COVID-19 pneumonia. In a subgroup of patients admitted in ICU, fibrocytes were quantified in blood and broncho-alveolar lavage (BAL). Serum amyloid P (SAP), TGF-b1,CXCL12, CCL2, and FGF2 serum concentration were measured in serum. We included 57 patients in the Hospitalized group (median age 59 years [23-87]) and 16 Healthy controls. The median percentage of circulating fibrocytes was higher in patients compared to controls (3.6% [0.2-9.2] vs. 2.1% [0.9-5.1], p=0.04). Blood fibrocyte count was lower in the 6 patients who died compared to survivors (1.6% [0.2-4.4] vs. 3.7% [0.6-9.2], p=0.02). Initial fibrocyte count was higher in patients showing a complete lung CT resolution at 3 months. Circulating fibrocyte count was decreased in the ICU group (0.8% [0.1-2.0]) whereas BAL fibrocyte count was 6.7% [2.2-15.4]. Serum SAP and TGF-b1 concentrations were increased in Hospitalized patients. SAP was also increased in ICU patients. CXCL12 and CCL2 were increased in ICU patients, and negatively correlated with circulating fibrocyte count. We conclude that circulating fibrocytes were increased in patients hospitalized for COVID-19 pneumonia and a lower fibrocyte count was associated with an increased risk of death and a slower resolution of lung CT opacities.

Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus

Serum amyloid P component (SAP, also known as Pentraxin 2; APCS gene) is a component of the humoral arm of innate immunity involved in resistance to bacterial infection and regulation of tissue remodeling. Here we investigate the role of SAP in antifungal resistance. Apcs−/− mice show enhanced susceptibility to A. fumigatus infection. Murine and human SAP bound conidia, activate the complement cascade and enhance phagocytosis by neutrophils. Apcs−/− mice are defective in vivo in terms of recruitment of neutrophils and phagocytosis in the lungs. Opsonic activity of SAP is dependent on the classical pathway of complement activation. In immunosuppressed mice, SAP administration protects hosts against A. fumigatus infection and death. In the context of a study of hematopoietic stem-cell transplantation, genetic variation in the human APCS gene is associated with susceptibility to invasive pulmonary aspergillosis. Thus, SAP is a fluid phase pattern recognition molecule essential for resistance against A. fumigatus.

Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice

SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis in animal models and clinical trials. Here we show that aspiration of the GU-rich ssRNA oligonucleotide ORN06 into mouse lungs induces all of the above COVID-19-like symptoms. Men tend to have more severe COVID-19 symptoms than women, and in the aspirated ORN06 model, male mice tended to have more severe symptoms than female mice. Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1β, IL-6, IL-12p70, IL-23, and IL-27 in serum. SAP also reduced D-dimer levels in the lung fluid. In human peripheral blood mononuclear cells, SAP attenuated ORN06-induced extracellular accumulation of IL-6. Together, these results suggest that aspiration of ORN06 is a simple model for both COVID-19 as well as cytokine storm in general, and that SAP is a potential therapeutic for diseases with COVID-19-like symptoms and/or a cytokine storm.

MTX Treatment Does Not Improve Outcome in Mice with AMI

<b><i>Background:</i></b> Targeting inflammation in patients with coronary artery disease and/or acute myocardial infarction (AMI) is a matter of debate. Methotrexate (MTX) is one of the most widely used immunosuppressants. Cardiovascular Inflammation Reduction Trial (CIRT) recently failed to demonstrate reduced cardiovascular events in MTX-treated patients. However, it is not known if long-term MTX treatment improves cardiac outcome in AMI. Therefore, in this study, we investigated the postischemic phase in MTX-treated mice undergoing AMI. <b><i>Methods:</i></b> Wild-type mice received MTX medication intraperitoneally for 2 weeks. Afterward, AMI was induced by transient left anterior ascending artery ligation. Postischemic cardiac damage after 24 h was assessed. <b><i>Results:</i></b> MTX treatment did not affect infarct size as compared to control (IS/AAR: Con 76.20% ± 12.37%/AAR vs. MTX 73.51 ± 11.72%/AAR, <i>p</i> = 0.64). Moreover, systolic function and structural parameters did not differ between groups (_24hejection fraction: Con 36.49 ± 3.23% vs. MTX 32.77 ± 2.29%, <i>p</i> = 0.41; _24hLVID; d: Con 3.57 ± 0.17 mm vs. MTX 3.19 ± 0.13 mm, <i>p</i> = 0.14). Platelets were increased by MTX (Con 1,442 ± 69.20 × 10³/mm³ vs. MTX 1,920 ± 68.68 × 10³/mm³, <i>p</i> &#x3c; 0.0001). White blood cell and RBC as well as rate of monocytes, granulocytes, lymphocytes, and serum amyloid P levels were equal. <b><i>Conclusion:</i></b> MTX medication did not improve postischemic cardiac damage in a murine model of AMI. Future trials are needed to identify and investigate other anti-inflammatory targets to improve cardiovascular outcome.