Distinct Regulation of EZH2 and its Repressive H3K27me3 Mark in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is an aggressive skin cancer for which Merkel cell polyomavirus integration and expression of viral oncogenes small T and Large T have been identified as major oncogenic determinants. Recently, a component of the PRC2 complex, the histone methyltransferase enhancer of zeste homolog 2 (EZH2) that induces H3K27 trimethylation as a repressive mark has been proposed as a potential therapeutic target in MCC. Because divergent results have been reported for the levels of EZH2 and trimethylation of lysine 27 on histone 3, we analyzed these factors in a large MCC cohort to identify the molecular determinants of EZH2 activity in MCC and to establish MCC cell lines' sensitivity to EZH2 inhibitors.

Leprosy as immune reconstitution inflammatory syndrome in patients living with HIV: Description of French Guiana's cases over 20 years and systematic review of the literature.

Background: HIV infection is highly prevalent in French Guiana, a territory where leprosy is also endemic. Since the introduction of Highly Active Antiretroviral Treatment (HAART) in the management of HIV, leprosy has been reported as part of the immune reconstitution inflammatory syndrome (IRIS).

Methodology/principal Findings: We aimed to present a general description of these forms of leprosy as IRIS, highlighting clinical and therapeutic specificities.

ELA/APELA precursor cleaved by furin displays tumor suppressor function in renal cell carcinoma through mTORC1 activation.

Apelin is a well-established mediator of survival and mitogenic signaling through the apelin receptor (Aplnr) and has been implicated in various cancers; however, little is known regarding Elabela (ELA/APELA) signaling, also mediated by Aplnr, and its role and the role of the conversion of its precursor proELA into mature ELA in cancer are unknown. Here, we identified a function of mTORC1 signaling as an essential mediator of ELA that repressed kidney tumor cell growth, migration, and survival. Moreover, sunitinib and ELA showed a synergistic effect in repressing tumor growth and angiogenesis in mice.

Inactivation of Proprotein Convertases in T Cells Inhibits PD-1 Expression and Creates a Favorable Immune Microenvironment in Colorectal Cancer.

Proprotein convertases (PC) activate precursor proteins that play crucial roles in various cancers. In this study, we investigated whether PC enzyme activity is required for expression of the checkpoint protein programmed cell death protein 1 (PD-1) on cytotoxic T lymphocytes (CTL) in colon cancer. Although altered expression of the PC secretory pathway was observed in human colon cancers, only furin showed highly diffuse expression throughout the tumors.

ApoE-fragment/Aβ heteromers in the brain of patients with Alzheimer's disease.

Identification of endogenous pathological amyloid β peptides (Aβ) forms in the brains of patients with Alzheimer's disease (AD) is still unclear. In healthy brain, Aβ can associate with Apolipoprotein E (ApoE) which is involved in its metabolism and clearance. In the brain of patients with AD, ApoE is cleaved and produces ApoE fragments.

Glial markers and emotional memory in rats following acute cerebral radiofrequency exposures.

The widespread mobile phone use raises concerns on the possible cerebral effects of radiofrequency electromagnetic fields (RF EMF). Reactive astrogliosis was reported in neuroanatomical structures of adaptive behaviors after a single RF EMF exposure at high specific absorption rate (SAR, 6 W/kg). Here, we aimed to assess if neuronal injury and functional impairments were related to high SAR-induced astrogliosis.