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PCTR1, via the activation of the lipoxin A4 receptor, promotes the conversion of linoleic acid to arachidonic acid (AA) through upregulation of the desaturases FADS1, FADS2, and ELOVL2 expression. It also inhibits the conversion of bound AA into free AA through downregulation of phospholipase A2 expression, resulting in decreases in serum AA and prostaglandin E2 levels, resulting in an anti-inflammatory effect and organ protection.
Synovial mesenchymal stem cells (MSCs) are an attractive cell source for transplantation in the meniscus of the knee because of their high chondrogenic potential. This study describes the morphological features of synovial MSC adhesion to the meniscus and provides ways to increase the number of adherent MSCs so that clinical outcomes can be improved.
ERdj3 (DNAJB11) and mesencephalic astrocyte-derived neurotrophic factor (MANF) are endoplasmic reticulum chaperones that may be secreted extracellularly. The authors demonstrate that in glomerulopathies with podocyte injury (passive Heymann nephritis and puromycin aminonucleoside nephrosis), these chaperones are secreted into the urine. The chemical chaperone, 4-phenyl butyrate (PBA) protects against podocyte injury and the therapeutic response could be monitored by urinary ERdj3 and MANF.
SiO2-mediated epithelial–mesenchymal transition via the nuclear transcription factor Ets-like protein-1 (ELK-1) due to oxidative stress and the downstream signaling of ZC3H4 expression. These findings suggest that the nuclear transcription factor ELK-1 may be useful as a novel target for the treatment of pulmonary fibrosis.
Changes in DNA methylation contribute to the pathogenesis of cardiovascular disease, including dilated cardiomyopathy and heart failure, by regulating gene expression. The authors show that DNA methyltransferase 1 deficiency in the myocardium restricts the reprogramming of genes and activates pathways involved in myocardial protection and apoptosis in response to pathological stress.
Generation of peptide fragments by oxidation of hemoglobin to ferryl hemoglobin occurs in ruptured atherosclerotic lesion in human and in intraventricular hemorrhage of brain in preterm infants. Peptide fragments of hemoglobin provoke intercellular gap formation and enhance monocyte adhesion to endothelial cell. Activation of endothelium via NF-κβ leads to TNF and IL-1β production, induction of NLRP3 and CASP1.
Using three-dimensional followed by two-dimensional culture, the authors generated the first reported cell line from a human pancreatic intraductal tubulopapillary neoplasm, a distinct precancerous lesion. They performed in-depth molecular analysis of the cell line and characterized its tumorigenic potential using multiple in vitro and in vivo assays.
Glycodelin is a major endometrial glycoprotein. The authors analyzed glycan structures of endometrial carcinoma associated glycodelin and established a novel glycodelin-glycoform specific histochemical staining method. With this, they showed that glycodelin is differentially glycosylated in endometrial carcinoma tissue, as compared to normal endometrium, representing a neoantigen with potential clinical applications.