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To investigate genetic homozygosity in pediatric teratomas, this study analyses 13 sacrococcygeal, 12 ovarian, and 3 testicular teratomas in children by short tandem repeat (STR) genotyping. While genetic homozygosity is frequent in adult ovarian teratomas, no evidence of genetic homozygosity is seen in patients younger than 4 years, arguing pediatric teratomas arise at an earlier stage of germ cell development.
The authors show that exposure of neonatal mice to the toxin biliatresone creates an animal model of biliary atresia. Such mice develop clinical signs of biliary obstruction, inflammatory cell infiltration and liver fibrosis.
HNRNPA2B1 regulates the splicing of MST1R and promotes the expression of a cancer-specific isoform, RON∆165, in head and neck cancer cells. RON∆165 activates the Akt/PKB pathway and leads to increased expression of epithelial to mesenchymal transition regulators such as TWIST2, E-cadherin, vimentin, and ZEB1 and promotes the invasive behavior of head and neck cancer.
Accurate quantification of steatosis in liver biopsies is a key step in the treatment of patients with fatty liver diseases. To assist pathologists for such analysis tasks, we develop a novel deep learning-based framework to segment overlapped steatosis droplets in whole slide liver biopsy images. Quantitative measurements of steatosis at both pixel and object-level present strong correlation with clinical data, suggesting its potential for clinical decision support.
Detailed protocols for immunohistochemical and in situ hybridization assays for the detection of SARS-CoV-2 are provide so they can be readily implemented in pathology laboratories and medical examiner offices for diagnostic and research purposes. These assays were found to represent a sensitive and specific method for detecting the virus in tissue samples.
PCP4/PEP19 knockdown in neuroblastoma cells induce neurite outgrowth, upregulation of NeuroD1 and downregulation of Ascl1 expression, suggesting that PCP4/PEP19 can suppress neurite outgrowth and neuronal differentiation through the regulation of NeuroD1 and Ascl1. Immunohistochemistry shows nuclear localization of PCP4/PEP19 in neuroblastoma cells. PCP4/PEP19 may therefore be an intranuclear negative regulator of neuronal differentiation.
The therapeutic effects of CP-25 on experimental Sjögren’s syndrome has been shown to be associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. The study provides an experimental foundation for CP-25 as a potential drug in the treatment of human autoimmune disorder, Sjögren’s syndrome.
Liquid biopsy is a novel promising, but technically challenging tool in oncology. We compared various circulating DNA extraction and sequencing systems used within four Swiss laboratories. Results were highly congruent, with perfect sensitivity down to 1% mutation frequency. We also determined several key factors to validate when implementing such tests.
The authors demonstrate that cholestasis impairs hepatic lipid storage via AMP-activated protein kinase (AMPK) and CREB signaling in hepatitis B virus surface protein transgenic mice. The pharmacological modulation of AMPK and CREB signaling might be a promising therapeutic concept for the treatment of fatty liver diseases.
MiR-126-5p expression decreases abdominal aorta dilation in mice with Ang II-induced abdominal aortic aneurysm (AAA), and its agomirs limit experimental AAA formation. MiR-126-5p inhibits Ang II- and PDGF-BB-induced dedifferentiation of aortic smooth muscle cells (AoSMCs) in vitro. MiR-126-5p promotes contractile switching of AoSMCs exposed to Ang II by targeting VEPH1.
This study reports novel pro-tumorigenic functions for CD38 in cancer associated fibroblasts (CAFs). In vivo, CAF CD38 promotes melanoma expansion. Mechanistically, CD38 enhances CAF migration towards cancer cells as well as tumor cell migration and invasion. Further, CD38 enables de novo endothelial tube formation by upregulating angiogenic transcripts and pro-angiogenic secreted factors.
An orally infected hamster model of Coxsackievirus A16 (CV-A16) hand-foot-and-mouth disease (HFMD) and encephalomyelitis demonstrating central nervous system and squamous epithelial infection, reminiscent of complicated human CV-A16 HFMD is described. This novel and consistent animal model should be useful to investigate viral pathogenesis, model person-to-person transmission, and to test antivirals and vaccines.
Proteomic profiling may contribute to the analysis and classification of cancer. The authors applied the digital western blot technique DigiWest with a panel of 102 proteins and phosphoproteins in combination with a machine learning algorithm to classify the tissue origin of five common cancer types in fresh frozen and formalin-fixed paraffin-embedded tissue. DigiWest profiling represents a valuable method for cancer classification, yielding conclusive and decisive data, thus making this approach attractive for routine clinical applications.
The authors demonstrate that mechanical strain enhances proliferation and migration of breast cancer (BCa) cells. Oscillatory strain (OS)-exposed triple negative breast cancer cells produced more exosomes with immunomodulatory potential. Preconditioning BCa cells with OS before transplantation in vivo increased tumor growth, infiltration of immunesuppressive myeloid-lineage cells, and enhanced exosome-mediated cellular cross-talk.
Fibronectin 1 (FN-1) promotes differentiation and mineralization of osteoblasts by activating the WNT/β-catenin pathway. Integrin β1 (ITGB1) acts as an indispensable signaling molecule for the interplay between FN-1 and β-catenin. Treatment with FN-1 and ITGB1 is a potential therapeutic strategy for improvement of bone formation in osteoporosis.
This study reveals that miR-185-5p alleviates endoplasmic reticulum (ER) stress, prevents epithelial dedifferentiation and subsequently improves renal fibrosis by downregulating activating transcription factor 6 (ATF6). The miR-185-5p/ATF6 pathway is proposed as a novel regulatory mechanism for renal fibrosis and may provide a therapeutic strategy for renal fibrosis associated with ER stress.
The authors developed an in vivo model to assess patterns of peritoneal dissemination of colorectal cancer cell lines that recapitulates the high heterogeneity observed between patients. Great variation in the extent of peritoneal outgrowth, localization and clonal dynamics between cell lines was observed and a putative association with KRAS pathway activation was identified.
This study aims to classify histopathological images of malignant lymphoma through deep learning. The classifier achieved the high levels of accuracy in comparison to diffuse large B-cell lymphoma, follicular lymphoma, and reactive lymphoid hyperplasia, which were higher than those of pathologists. Artificial intelligence can potentially support diagnosis of malignant lymphoma.
This study examined the contribution of ACE2 in diabetes onset and the role of ACE2 in the progression of diabetic nephropathy in NOD mouse. ACE2 loss leads to an impaired glucose and insulin homeostasis, RAS activation, increase in oxidative stress, and RIPK1 within the pancreas. In the kidney, ACE2 deletion induced podocyte loss, RAS modulation, and renal fibrosis activation in an early phase of diabetes.