Explore the vast range of titles available.

Inflammatory and oncogenic signaling converge in disease evolution of BCR–ABL-negative myeloproliferative neoplasms, clonal hematopoietic stem cell disorders characterized by gain-of-function mutation in JAK2 kinase (JAK2V617F), with highest prevalence in patients with polycythemia vera (PV). Despite the high risk, DNA-damaging inflammatory microenvironment, PV progenitors tend to preserve their genomic stability over decades until their progression to post-PV myelofibrosis/acute myeloid leukemia. Using induced pluripotent stem cells-derived CD34 + progenitor-enriched cultures from JAK2V617F + PV patient and from JAK2 wild-type healthy control, CRISPR-modified HEL cells and patients’ bone marrow sections from different disease stages, we demonstrate that JAK2V617F induces an intrinsic IFNγ- and NF-κB-associated inflammatory program, while suppressing inflammation-evoked DNA damage both in vitro and in vivo. We show that cells with JAK2V617F tightly regulate levels of inflammatory cytokines-induced reactive oxygen species, do not fully activate the ATM/p53/p21waf1 checkpoint and p38/JNK MAPK stress pathway signaling when exposed to inflammatory cytokines, suppress DNA single-strand break repair genes’ expression yet overexpress the dual-specificity phosphatase (DUSP) 1. RNAi-mediated knock-down and pharmacological inhibition of DUSP1, involved in p38/JNK deactivation, in HEL cells reveals growth addiction to DUSP1, consistent with enhanced DNA damage response and apoptosis in DUSP1-inhibited parental JAK2V617F + cells, but not in CRISPR-modified JAK2 wild-type cells. Our results indicate that the JAK2V617F + PV progenitors utilize DUSP1 activity as a protection mechanism against DNA damage accumulation, promoting their proliferation and survival in the inflammatory microenvironment, identifying DUSP1 as a potential therapeutic target in PV.

Sodium chloride is widely used in aquaculture due to its antiparasitic effects and its ability to reduce stress during fish transport and manipulation. The aim of this study was to assess the safety of short-term exposure to sodium chloride for the common carp ( ). In our experiment, fish were placed into a sodium chloride bath (c = 30 g l ; T = 30 min; t = 20 °C) and the effects of the treatment were assessed immediately after the bath (T0) and 24, 48 and 240 h later (T24, T48 and T240, respectively), with non-treated fish serving as control groups. Though significant differences compared to the controls were observed in the treated fish sampled at T0, T24 and T48, these effects were only temporary and all the affected parameters (i.e., haemoglobin, haematocrit, plasmatic lactate, cholesterol, alanine aminotransferase, albumin, phosphorus and ceruloplasmin) had completely recovered within 10 days of exposure, suggesting that the treatment of carp with a sodium chloride bath represents a safe approach suitable for therapy of parasitic infections.