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The hedgehog pathway is pivotal in basal cell carcinoma and medulloblastoma development. Gorlin syndrome-derived, induced pluripotent stem cells (iPSCs) carrying a heterozygous mutation in PTCH1, a hedgehog target gene, exhibited high GLI1 expression and enhanced sensitivity to a hedgehog pathway inhibitor after neural differentiation. These iPSCs can serve as a model for hedgehog pathway-related tumors.
Digital image analysis (DIA) of multiplex fluorescence-based immunohistochemistry and visual chromogenic evaluation of CDX2, SOX2, SOX9, E-cadherin, and β-catenin in colorectal cancer are comparable, recognizing prognostic value of CDX2 and negative correlation with SOX2. Membrane staining is best evaluated visually, while DIA enables single-cell coexpression analysis and improves visualization and detection of clinicopathological and biological associations.
The authors designed an adapter multiplex PCR amplicon with multiple domain melting curves to rapidly detect and genotype at least 20 ALK fusion variants in one tube with HRM. In addition, they introduced feature extraction of the second derivative curve to assist visual analysis to automatically discriminate ALK fusion variants.
The authors examined the capability of propagation-based phase-contrast tomography (PB-PCT) with single-distance phase retrieval for longitudinal in vivo monitoring of bone changes using monochromatic synchrotron light. The application of PB-PCT to the measurement of bone defect healing in mice demonstrated its potential for tracking volumetric and mineral-density changes in newly formed bone.
Bone marrow aspirate (BMA) differential cell counts (DCCs) are critical for classification of hematologic disorders. Manual DCCs are still considered the gold standard as a reliable automated method is yet to be developed. Digital pathology and machine learning represent a highly promising technology for this purpose. The authors report their experience developing machine learning algorithms to detect and classify BMA cells. Promising early results signify an important initial step in the effort to devise a reliable, objective method to automate DCCs.
The paper describes a fully automated numerical analysis for an unbiased quantification of non-alcoholic fatty liver disease (NAFLD) histological features in rodent models. The technique offers a quantitative high-throughput method to rapidly detect NAFLD in large preclinical studies and for accurately monitoring disease evolution.
This study shows a negative regulation of autophagy-related RNA transcripts and the upregulation and downregulation of p62 and LC3-B proteins, respectively, in the central nervous system of scrapie-infected transgenic mice at clinical stage. These findings likely reflect an impairment of the autophagic pathway at the late symptomatic stage of prion infection.
The NanoSuit method permits the study of paraffin sections using correlative light and electron microscopy at low and high magnification, with the following features: (i) the integrity of the glass slide is maintained, (ii) 3D microstructures of tissue and pathogens can be visualized, (iii) nuclei and 3,3′-diaminobenzidine-stained areas are distinct because of gold chloride usage, (iv) immunohistochemical staining is quantitative, and (v) contained elements can be analyzed.
In chondrocytes, TGF-β1 increases the expression of hypertrophic genes, suggesting that this treatment could mimic osteoarthritis in vitro. EZH2 and Sik3 inhibition, as well as HIF induction repress the expression of hypertrophy markers in TGF-β stimulated chondrocytes, validating the reliability of this model to predict anti-hypertrophic effects of drugs.
We describe generation of neuroblastoma cell lines using conditional reprogramming (CR)—new cell culture method that allows indefinite propagation of cells in an undifferentiated state. We optimized CR growth conditions for neuroblastoma tissue and grew mouse neuroblastoma cells in vitro. These cells demonstrate a unique phenotype, are positive for neuroblastoma markers, and can be passaged and biobanked for continued studies.
The authors provide a side-by-side comparison of morphology and function of primary ductal fragments isolated from mouse pancreas and pancreatic organoid cultures. Using state-of-the-art techniques, they demonstrate that pancreatic organoids can be a suitable and robust model to study pancreatic ductal epithelial ion transport in health and disease.
The authors propose that Wisteria floribunda agglutinin (WFA) staining on failing heart sections may be useful for quantitative assessment of cardiac fibrogenic activity. The fibrosis-specific WFA staining is mainly due to the WFA binding to fibrogenesis-related extracellular matrix N-glycoproteins. It is expected that cardiac WFA-binding glycoproteins may be circulating glyco-biomarkers for cardiac fibrogenesis.
Protein misfolding cyclic amplification (PMCA) is a technique able to detect minute amount of disease-related prion protein (PrPD), but limited results have been obtained with human prions with the exception of variant Creutzfeldt-Jakob disease (variant CJD). The study demonstrates that the use of substrates with deglycosylated PrP strongly increases PrPD amplification efficiency by PMCA for all tested CJD subtypes. The enhanced PMCA efficiency may allow for the developing of a sensitive, non-invasive, diagnostic tests for the different CJD subtypes based on body fluids or easily accessible peripheral tissues.
The authors examined the feasibility of co-staining miRNAs by fluorescent miRNA in situ hybridization (miRisH) and their target proteins by immunohistofluorescence (IHF) on tissue microarrays from prostate cancer patients, which would allow for the study of miRNA expression patterns and their target proteins at the single-cell level. The miRNAs and corresponding target proteins include the pairs miR-145/ERG, miR-143/uPAR and miR-375/SEC23A.
The authors present the first in-depth analyses of liver pathology in a murine model of classical Farber disease. Characterizing their previously developed acid ceramidase-deficient Farber mice, they identify inflammation, fibrosis, and abnormal lipid profiles in livers/hepatocytes and highlight altered inflammatory, lipid, and sphingolipid gene expression pathways.
Mass spectrometry imaging (MSI) is a potential adjunct to histopathology. However, studies have yet to adequately test its performance and reliability. Using over 900 MSI spectra, the authors establish and validate an accurate, high-resolution metabolic profile of prostate cancer, supporting the incorporation of MSI tools into surgical pathology.
A new technical pipeline describes a combined approach of HER2/CEP17 fluorescence in situ hybridization (FISH) analysis with MALDI imaging on the very same section of formalin-fixed and paraffin-embedded (FFPE) tissue. Combining molecules detected by MALDI imaging with the gene copy number detected by HER2/CEP17 FISH, we found a synergistic effect which enhances patient prognosis.
In this paper, the authors dissected the temporal sequence of three early events in diabetic retinopathy. They show that vascular degeneration is the initiating cellular change during the development of retinopathy in the diabetic Nile rat. Focusing on vascular events, they conducted a detailed longitudinal study and showed that the Nile rat exhibits a wide range of retinal lesions remarkably similar to the human condition.