Volume 98 Issue 12, December 2018

Applying histological/histomorphometrical analyses on femora and/or lumbar vertebrae, as well as spectrometric and molecular methodologies on bone-marrow mesenchymal stem cells form APOE knock out and wild-type mice, the authors demonstrate that APOE deficient mice fed a Western-type diet have remarkably augmented bone-marrow adiposity and significantly reduced bone mass due to enhanced osteoclastic and impaired osteoblastic function.

Vitamin D insufficiency is associated with the severity of oxidative stress in vitiligo patients. This study provides new insights into the mechanism of vitamin D as a treatment for vitiligo; it protects melanocytes against oxidative stress by activating Wnt/β-catenin signaling. Targeting this signaling could be a useful approach to improve treatment for vitiligo.

In this study, a novel epidermal growth factor receptor (EGFR)-targeted, human β-defensin 1-tailored fusion protein, Ec-LDP-DF, and its enediyne-integrated analogue, Ec-LDP(AE)-DF, have been prepared by genetic engineering and molecular reconstitution. The fusion protein Ec-LDP(AE)-DF displays extremely potent cytotoxicity and might be highly effective for non-small cell lung cancer therapy and useful for other EGFR-targeted therapeutics.

This study demonstrates that lung mesenchymal stem cells promote non-small cell lung cancer proliferation and migration in a MAPK/translation initiation/autophagy-dependent manner. The authors describe how primary and metastatic niches display opposite and critical effects, both crucial to cancer progression.

DNA ligase I (LIG1), an essential enzyme implicated in DNA recombination and DNA repair, is modulated by the oncoprotein SRSF1. In non-small cell lung cancer (NSCLC) cells, LIG1 inhibition is associated with reduced proliferation and increased apoptosis. LIG1 expression is therefore a poor prognosis factor in NSCLC.

Cellular senescence induced by replication and an AKT inhibitor in ex-vivo spheroid leiomyomas was examined in this work. Several dysregulated genes in the ROS, hypoxic and AKT pathways were identified, including WIPI1 and SLITKR4. Induced senescence in spheroids can be reversed by ABT263, a BH3 mimetic, which may be therapeutic modality for treatment of leiomyoma.

In normal rats and a human hepatic cell line, the authors demonstrate that remifentanil upregulates IL-18BP expression in hepatocytes, and that the underlying mechanism involves activation of the transcription factors STAT1 and C/EBP β. These findings expand our understanding of the pharmacological effects of remifentanil and suggest its potential treatment benefits for IL-18 dysfunction-mediated hepatic diseases.

S3I-201, a chemical inhibitor of the transcription factor STAT3, suppresses liver fibrogenesis and angiogenesis through multiple mechanisms both in vitro and in vivo. Moreover, S3I-201 and sorafenib, an FDA-approved multikinase inhibitor, function synergistically in suppressing fibrogenesis and angiogenesis of human hepatic stellate cells, indicating high potential for liver fibrosis treatment.

Iso-alpha-acids (IAAs) are hops-derived compounds. In this study, the authors show that IAAs inhibit development of non-alcoholic fatty liver disease. They found that IAAs reduced expression of PPAR-γ and key enzymes of lipid synthesis as well as increased expression of PPAR-α, indicative of increased lipid metabolism. IAAs also reduced oxidative stress and JNK-activation, inhibited hepatic stellate cell activation and reduced proliferation and pro-fibrogenic gene expression.

As a central regulator of self-renewal and pluripotency maintenance in normal and neoplastic stem cells, transcription factor SOX2 expression is tightly controlled. The authors found that the histone-lysine N-methyltransferase MLL1/WDR5 complex methylates SOX2 at K42 and promotes its degradation. Conversely, the protein PHF20L1 recognizes methylated SOX2 through its MBT domain and blocks the degradation of SOX2.

Tumor cell-endothelial adhesion is one of the key steps for invasion and metastasis. The authors show that Gal-3 promotes cancer cell adhesion to vascular endothelial cells by increasing the expression of N-cadherin and CD44 via an increase of β-catenin nuclear accumulation. This new molecular mechanism of Gal-3-mediated cell adhesion may aid in the development of new strategies to prevent metastasis.

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.