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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.
The authors generated a CRISPR-Cas9 edited “workhorse” platform using a Ptf1-Cre; LSL-Cas9 mouse that. This model enables the relatively facile interrogation of the functional role of mutated genes in the pancreatic ductal adenocarcinoma landscape, including diverse combinations of targeted alleles using adeno-associated virus 8 as a delivery vector. The resulting pancreata demonstrate the full compendium of precursor and invasive lesions observed in human pancreatic ductal adenocarcinoma.
The authors developed a rat model for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), using a minimal future liver remnant considered to be insufficient for survival. An in situ split combined with portal vein ligation boosts liver hypertrophy, and hepatectomy induces a higher level of hepatocyte proliferation, resulting in increased liver mass recovery and survival after ALPPS. This robust model should be valuable for studying the physiological mechanisms leading to accelerated regeneration.
Theralin, which simultaneously fixes and decalcifies bone tissue, was compared with formalin fixation with acid decalcification in primary bone cancer cases. Use of theralin improved (a) sample processing time, (b) tissue histomorphology, (c) protein and DNA extractability, and (d) enabled standard FISH staining in bone. This unlocks the molecular archive within bone for the standard tissue analysis pipeline.
The authors developed a high-content, quantitative analysis of breast cancer tissues based on microfluidic staining and image processing, to characterize both HER2 overexpression and amplification at the cellular level. This study paves the way for evaluatation of intratumoral heterogeneity with unprecedented accuracy with standard staining methods such as immunofluorescence and FISH.
This paper describes mini-XPerT, a multiplexed screen to simultaneously measure cellular contraction, endothelial barrier function, and cytoskeletal and cell-cell junctional changes. It is the unique combination of these measurements that has enabled the authors to unveil the distinct biophysical mechanisms of barrier defense conferred by Y-27632 and Angpt-1. Mini-XPerT is likely to be applicable across the spectrum of basic and translational science - in mechanistic studies of the endothelium across numerous diseases, and for high-throughput drug discovery.
Endogenous circular RNA (circRNA) expression has not been characterized in B-cell malignancies, and current methods for circRNA quantification have several limitations. Here, the authors provide a map of circRNA expression in B-cell malignancies based on high-throughput RNA sequencing and present an enzyme-free digital counting methodology, which has the potential to become the gold standard for circRNA quantification.