Articles in 2020

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.

RNA of sufficient quality and quantity can be extracted from formalin-fixed paraffin-embedded (FFPE) samples to obtain comprehensive transcriptome profiling using the 3′ massive analysis of c-DNA ends (MACE) RNA-sequencing technology. Thus, MACE provides an opportunity for utilizing FFPE samples stored in histological archives.

This study provides insight into the function of Sox13 in hepatocellular carcinoma (HCC). Sox13 serves as a key regulator of HCC cell migration, invasion, and epithelial-to-mesenchymal transition by transactivating Twist1. Sox13 forms heterodimers with Sox5 to enhance Twist1 transcriptional activity. In addition, overexpression of Sox13 indicates poor prognosis for HCC patients. These findings implicate Sox13 as a potential therapeutic target for HCC.

This study reveals that inhibition of miR-181a-5p protects immature rats from epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, and oxidative stress. This protection is achieved through the SIRT1 pathway, which may be a novel therapeutic target for epilepsy.

Medulloblastoma (MB) cells form three-dimensional tumoroids in vitro that can be passaged and preserved. MB cells in tumoroids retain the tumorigenic potential and hedgehog signaling, which relies on stromal astrocytes and astrocyte-derived extracellular matrix. These findings provide a valuable cell model for the basic and preclinical studies of MB.

The authors. show that CCL3 derived from both tumor-associated macrophages and esophageal squamous cell carcinoma (ESCC) cells promotes cell migration and invasion of ESCC cells via binding CCR5. High expression of CCL3 and/or CCR5 associates with poor prognosis in ESCC patients. CCL3–CCR5 axis could be a specific target of anti-cancer therapy.

The authors developed a novel simplified assay for glioblastoma transcriptional classification on formalin-fixed-paraffin-embedded tissue samples. On such dataset, immunohistochemical profiles, based on expression of a restricted panel of gene classifiers, were integrated by machine learning approach to generate a glioblastoma transcriptional signature based on protein quantification that allowed to efficiently assign transcriptional subgroups to an extended cohort. Correlations with both histopathological features and clinical outcome have been also performed.

Intestinal farnesoid X receptor (FXR) deficiency in mice leads to more severe liver injury and inflammation with ethanol treatment, which is associated with increased intestinal leakage. These results suggest that intestinal FXR may be critical in maintaining gut integrity and the epithelial barrier to protect the liver from ethanol-induced injury.

Wolfram syndrome is a prototype of endoplasmic reticulum (ER) stress disorder characterized by diabetes, visual impairment, and neurodegeneration. Currently, there is no treatment that can halt or reverse the disease progression. Here, the authors show that mesencephalic astrocyte-derived neurotrophic factor-based regenerative gene therapy is an emerging therapeutic strategy for Wolfram syndrome and other ER stress-related disorders.