Volume 101 Issue 12, December 2021

Chronic mineral-oil intraperitoneal administration induces hepatic inflammation through innate immune responses via myeloid cell activation. Lcn2 null mice develop less inflammation due to defective genes involved in myeloid cell activation, and downregulated gene sets for collagen-containing extracellular matrix, leading to mitigation of the liver fibrosis. Lcn2 null mice show enriched expression of genes responsible for DNA damage and cell cycle DNA replication compared to wild-type upon chronic CCl₄ liver injury.

Nonalcoholic fatty liver disease is the most common cause of chronic liver disease globally and a risk factor for hepatocellular carcinoma. The study highlights the role of miR-155 in nonalcoholic steatohepatitis. miR-155-deficient mice displayed overall protection from diet-induced steatohepatitis and fibrosis. Therapeutic inhibition of miR-155 might be effective approach for treatment of nonalcoholic steatohepatitis.

In this article the authors demonstrate that monomeric C reactive protein (mCRP) increases NOS2, COX2, MMP13, VCAM1, IL-6, IL-8, and LCN2 expression in chondrocytes. mCRP exerts a sustained catabolic effect on chondrocytes, increasing the expression of inflammatory mediators and proteolytic enzymes, which can promote cartilage extracellular matrix breakdown and osteoarthritis development and progression.

The authors present a robust diagnostic algorithm based on digital pathology and image analysis that quantifies intratumoral and stromal CD8+ T-cell densities in the tumor center and invasive margin compartment in metastatic melanoma. Spatial CD8+ T-cell densities are translated into the clinically relevant immune diagnostic categories “inflamed”, “excluded”, and “desert”. Their approach also allows efficient immune phenotyping of metastatic lesions, on biopsy material or even in the absence of material from the invasive margin.

Extensive morphological analysis demonstrates the importance of tunneling nanotubes for intercellular communication in osteoclast differentiation, especially in the fusion process of osteoclast precursors. Successful detection of nanotubes was also demonstrated in cultured primary osteoclasts resorbing dentin slices, and in osteoclasts in bone destruction sites of arthritic rats. Tunneling nanotubes are important for the differentiation of osteoclasts, both in vitro and in vivo.

An osteosarcoma-specific exosomal gene signature was developed using an orthotopic. xenograft model with a species-differentiating bioinformatics pipeline. The gene signature was validated in the serum of dogs with osteosarcoma, where it was able to detect minimal residual disease, and was therefore associated with prognosis following treatment.

The authors investigated the contribution of yes associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in osteocyte mechanotransduction. In a 3-D osteocyte compression model, they show that YAP/TAZ signaling is activated, is required for osteocyte mechano-responsiveness, and regulates the expression profile of target genes as shown by RNAseq analysis and the control of chemokine expression.

A novel assay quantifies depolarization of synaptosomes from Alzheimer’s cortex, and the authors show that tau released from these samples is unphosphorylated and C-terminal-truncated. Most tau is exosomal, and free-floating tau did not seed aggregation. Seeding activity was lower in tauopathy than AD, and strongly related to amyloid level.

The authors found that size selection magnetic beads could remove long RNA transcripts from total RNA with simplistic operation. After long transcript removal, microRNA could be concentrated and efficiently reverse-transcribed by stem-loop-6N primer. Touchdown qPCR improved microRNA quantification with lower C_T values and better detection efficiency. Finally, they incorporated these observations and created a new protocol named long transcripts minus touchdown qPCR for screening and quantifying microRNAs.

The authors demonstrate in vitro CRISPR/CAS9-mediated editing of the canine adenovirus type 2 (CAV2) genome to successfully insert a red fluorescent protein reporter construct and to replace E3 gene sequences with a single domain antibody in the CAV2 genome. This work provides a significantly improved and efficient method for targeted editing of adenoviruses to generate altered and potentially therapeutic viral genomes in the shortest possible time.