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Siglec-15 is normally expressed by myeloid cells and upregulated in some human cancers and represents a promising new target for immunotherapy. The aim of this study was to develop an immunohistochemical assay for Siglec-15 to be used as a companion diagnostic for future clinical trials. Here, the authors created and validated an assay with a novel recombinant antibody to the cytoplasmic domain of Siglec-15. This study may support development of a companion diagnostic assay to enrich for patients expressing the Siglec-15 target for therapy.
Circular RNAs (circRNAs) play important roles in many lung diseases. This study investigated the role of circHECTD1 in acute lung injury (ALI). circHECTD1 attenuates the apoptosis of alveolar epithelial cells in lipopolysaccharide-induced ALI through the miR-320a/PIK3CA and miR-136/Sirt1 pathways, indicating a novel therapeutic target for ALI.
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.
Multiplexed ion beam imaging by time-of-flight (MIBI-TOF) uses secondary ion mass spectrometry to image dozens of proteins simultaneously in the same tissue section. The authors undertook a validation study, assessing concordance across serial sections of a tissue microarray that were independently imaged by MIBI-TOF or single-plex immunohistochemistry. They demonstrate that MIBI-TOF can generate consistent and quantitative annotations of clinically relevant cell states in archival human tissue and present a scalable framework for benchmarking multiplexed immunohistochemical approaches.
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.
Soft tissue sarcomas are rare and aggressive neoplasms with limited models for laboratory-based studies. This study established eight models of soft tissue sarcomas, three malignant peripheral nerve sheath tumors, four undifferentiated pleomorphic sarcomas, and one unclassified spindle cell sarcoma. The new sarcoma cell lines are tools to elucidate molecular aberrations and improve treatment options for these difficult-to-treat sarcomas.
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.