Kynurenic acid, a key L-tryptophan-derived metabolite, protects the heart from an ischemic damage.

Background: Renal injury induces major changes in plasma and cardiac metabolites. Using a small- animal in vivo model, we sought to identify a key metabolite whose levels are significantly modified following an acute kidney injury (AKI) and to analyze whether this agent could offer cardiac protection once an ischemic event has occurred.

Methods And Results: Metabolomics profiling of cardiac lysates and plasma samples derived from rats that underwent AKI 1 or 7 days earlier by 5/6 nephrectomy versus sham-operated controls was performed.

The antipsychotropic drug Duloxetine rescues PAX6 haploinsufficiency of mutant limbal stem cells through inhibition of the MEK/ERK signaling pathway.

Aniridia is a panocular disease causing progressive severe visual impairment and blindness due to PAX-6 haploinsufficiency. One of the most disabling ocular symptoms is aniridia-related keratopathy (ARK), a progressive corneal opacification due to epithelial impairment, vascular and conjunctival pathologies. There is currently no available treatment to prevent progressive visual loss.

Ritanserin, a potent serotonin 2A receptor antagonist, represses MEK/ERK signalling pathway to restore PAX6 production and function in aniridia-like cellular model.

Aniridia is a panocular inherited rare eye disease linked to heterozygous mutations on the PAX6 gene, which fail to properly produce sufficient protein essential for normal eye development and function. Most of the patients suffer from aniridia-related keratopathy, a progressive opacification of the cornea. There is no effective treatment for this blinding disease.

Continuous Inflammatory Stimulation Leads via Metabolic Plasticity to a Prometastatic Phenotype in Triple-Negative Breast Cancer Cells.

Chronic inflammation promotes cancer progression by affecting the tumor cells and their microenvironment. Here, we demonstrate that a continuous stimulation (~6 weeks) of triple-negative breast tumor cells (TNBC) by the proinflammatory cytokines tumor necrosis factor α (TNFα) + interleukin 1β (IL-1β) changed the expression of hundreds of genes, skewing the cells towards a proinflammatory phenotype. While not affecting stemness, the continuous TNFα + IL-1β stimulation has increased tumor cell dispersion and has induced a hybrid metabolic phenotype in TNBC cells; this phenotype was indicated by a transcription-independent elevation in glycolytic activity and by increased mitochondrial respiratory potential (OXPHOS) of TNBC cells, accompanied by elevated transcription of mitochondria-encoded OXPHOS genes and of active mitochondria area.

Persistent Inflammatory Stimulation Drives the Conversion of MSCs to Inflammatory CAFs That Promote Pro-Metastatic Characteristics in Breast Cancer Cells.

The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo conversion at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity.

Mutated in its Ortholog Recapitulates Neuronopathic Gaucher Disease.

Gaucher disease (GD) results from mutations in the gene, which encodes lysosomal glucocerebrosidase (GCase). The large number of mutations known to date in the gene lead to a heterogeneous disorder, which is divided into a non-neuronopathic, type 1 GD, and two neurological, type 2 and type 3, forms. We studied the two fly orthologs, and .

Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles.

Azole antifungals inhibit the biosynthesis of ergosterol, the fungal equivalent of cholesterol in mammalian cells. Here we report an investigation of the activity of coumarin-substituted azole antifungals. Screening against a panel of Candida pathogens, including a mutant lacking CYP51, the target of antifungal azoles, revealed that this enzyme is inhibited by triazole-based antifungals, whereas imidazole-based derivatives have more than one mode of action.

Correction: Past1 Modulates Drosophila Eye Development.

[This corrects the article DOI: 10.1371/journal.pone.

Past1 Modulates Drosophila Eye Development.

Endocytosis is a multi-step process involving a large number of proteins, both general factors, such as clathrin and adaptor protein complexes, and unique proteins, which modulate specialized endocytic processes, like the EHD proteins. EHDs are a family of Eps15 Homology Domain containing proteins that consists of four mammalian homologs, one C. elegans, one Drosophila melanogaster and two plants orthologs.