Volume 100 Issue 9, September 2020

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.

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.

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.

Thrombospondin-1 (TSP1) is a matrix protein that binds it high affinity receptor CD47. Both TSP1 and CD47 are upregulated in the kidney in response to injury and this promotes the development of fibrosis by inducing transforming growth factor-β and other fibrogenic factors. The authors were able to block or eliminate CD47-based signal transduction to reduce renal fibrosis.

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.

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.

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.

The authors developed nervous-system-specific Nrbf2 knockout mice and found that they exhibited profound learning and memory deficits. RNAseq analyses have identified altered expression of genes related to protein folding and quality control. Aberrant aggregates of some of these key proteins are evident in the hippocampus.

This study on myxoid liposarcoma, based on mass spectrometry imaging of N-glycans, has revealed that increases in high-mannose-type as well as tri- and tetra-antennary complex-type N-glycans are associated with morphological progression of the disease. The increased abundance of tri-antennary complex-type glycans was also associated with a poor disease-specific survival for the patients.

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.