Articles

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.

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.

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.

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.

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.

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.

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 present study reveals that the hepatitis-B (HBV) antigen HBeAg found in HBV⁺HCC upregulates long non-coding RNA MAPKAPK5_AS1 (MAAS) expression in M2 macrophages by affecting its m6A modification. MAAS is transferred to HBV⁺HCC cells via exosomes, which in turn facilitates their proliferation. This is a novel role for MAAS and further elucidates the mechanism of HBeAg-induced HBV-related HCC development.

This study reveals that miR-483-5p is upregulated by cisplatin treatment and exacerbates cisplatin-induced acute kidney injury via negative regulation of GPX3 and contributes to tubular cell apoptosis. The authors demonstrate that miR-483-5p is a key upstream mediator regulating acute kidney injury induced by cisplatin and may serve as a new target for diagnosis and therapy.

Gastric cancer possesses great histological and molecular diversity, which creates obstacles for rapid and efficient diagnoses. To overcome the limitations of the classic diagnostic procedure in gastric cancer, the authors established a deep learning system to achieve intelligent tumor differentiation grading and microsatellite instability status recognition using hematoxylin-eosin stained whole slide images from 467 patients. They used the convolutional neural network visualization to demonstrate the key pathological features learned by the system to increase system interpretability.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin disease caused by mutations in the gene COL7A1. The authors developed a strategy to investigate the impact of each pathogenic mutation on skin integrity using CRISPR-mediated genome editing in mice in order to create a reliable animal model for the study of this devastating disease.

The authors show that LINC01963 is overexpressed in the PC3-DR cells and that LINC01963 silencing enhances the chemosensitivity of PC3-DR to docetaxel and inhibits tumorigenicity and lung metastasis. Silencing of LINC01963 ireduces TrkB protein levels to enhance the chemosensitivity of cells to docetaxel by competitively binding to miR-216b-5p.

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.

Mammals exhibit epidermal patterning, as seen in mouse tail scales and human skin microtopography. In this article, the authors demonstrate that type XVII collagen (COL17), a niche for epidermal stem cells, modulate epidermal patterning in mice and humans. COL17 further prevents wound-induced epidermal deformation. This study paves the way for elucidating the role of the stem cell niche in tissue pattern formation.