Volume 102 Issue 8, August 2022

The authors defined the role of DNA methyltransferase 1 (DNMT1) during heart failure and identified the underlying mechanism. DNMT1 enhances the methylation of the miR-152-3p promoter region. DNMT1 also enhances the expression of the transcription factor ETS1, which further elevates RhoH expression. DNMT1 therefore induces heart failure by inhibiting mitophagy of in H9c2 cells through regulating the miR-152-3p/ETS1/RhoH axis.

Bronchopulmonary dysplasia (BPD) is still the most common challenge in preterm neonates. The authors found that reactive oxygen species and sCD146 are increased in preterm peripheral blood samples. They then show that the CD146-HIF-1α axis contributes to alveolarization and propose that CD146 may be a novel candidate in BPD therapy.

Sickle cell disease (SCD) is associated with deficits in revascularization following vascular injury and the role of nitric oxide (NO) bioavailability in SCD vasculopathies is controversial. This study tests L-arginine and NO-hydrogel treatments in a model of vascular insufficiency and finds that neither therapy improves recovery in SCD mice. In fact, delivery of NO at the site of ischemia increases oxidative stress and worsens outcomes, highlighting potential limitations of NO-targeted therapeutics in SCD.

As the coronavirus disease 2019 (COVID-19) pandemic evolves, evidence has implicated the heart as a critical target of injury. We examined purported mechanisms of COVID-19-associated heart damage in 21 COVID-19-positive decedents, compared to clinically matched controls and other etiologies of viral myocarditis in a custom tissue microarray, via immunohistochemistry and in situ hybridization. Collectively, COVID-19-associated cardiac injury was multifactorial, with elevated levels of neutrophil extracellular traps and von Willebrand factor as defining features of direct and indirect viral-associated injury.

NORAD, a non-coding RNA activated by DNA damage, is highly expressed in osteosarcoma cells and tissue. The authors show that extracellular vesicles (EVs) derived from bone mesenchymal stem cells (BMSCs) deliver NORAD to osteosarcoma cells to regulate the miR-30c-5p/ Krueppel-like factor 10 axis, thereby accelerating the progression and metastasis of osteosarcoma.

In this study, the technical feasibility and the diagnostic value of SNP array analysis on 171 core needle biopsies (CNB) from soft tissue and bone tumors was evaluated. The analysis succeeded technically in 98% of the cases. The copy number profiles were compatible with the CNB diagnoses in 87% of the cases and was in 77% of the cases representative for the whole lesion.

As IL-34, a macrophage growth factor, is elevated in RA patients, it is considered a therapeutic target. Unexpectedly, inflammatory arthritis in IL-34 null mice and the newly identified IL-34 receptor, PTPRZ, null mice worsened disease. Through macrophage mediated mechanisms, IL-34 and PTPRZ-dependent events limited apoptotic neutrophil rich synovial inflammation and joint destruction. These findings counter the assumption that IL-34 is harmful in RA, and fuel further studies before designing a therapeutic approach for this illness.

The authors show that the energy-regulating peptide nesfatin-1 suppresses acidosis-induced oxidative stress, inflammation, and apoptosis in acid-stimulated chondrocytes and alleviates symptoms in rats with adjuvant-induced arthritis. Its mechanism may be related to its ability to decrease ASIC1a protein levels via the MAPK/ERK and NF-κB pathways.

Lupus nephritis can cause acute or chronic kidney damage. YY1, as a ubiquitously expressed transcription factor in mammals, plays a role in inflammation. This study shows that overexpression of YY1 reduces apoptosis, inhibits inflammation, and affects the ratio of Th17/Treg cells by regulating the IFN-γ/Fra2/PARP-1/FOXO1 axis, thereby repressing lupus nephritis-induced kidney damage.