Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties.

Ribosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from caudex, which has been named heterophyllin.

New Insights on Saporin Resistance to Chemical Derivatization with Heterobifunctional Reagents.

Saporin is a type 1 ribosome-inactivating protein widely used as toxic payload in the construction of targeted toxins, chimeric molecules formed by a toxic portion linked to a carrier moiety. Among the most used carriers, there are large molecules (mainly antibodies) and small molecules (such as neurotransmitters, growth factors and peptides). Some saporin-containing targeted toxins have been used for the experimental treatment of several diseases, giving very promising results.

Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering?

Immune checkpoint mechanisms are important molecular cell systems that maintain tolerance toward autoantigens in order to prevent immunity-mediated accidental damage. It is well known that cancer cells may exploit these molecular and cellular mechanisms to escape recognition and elimination by immune cells. Programmed cell death protein-1 (PD-1) and its natural ligand programmed cell death ligand-1 (PD-L1) form the PD-L1/PD-1 axis, a well-known immune checkpoint mechanism, which is considered an interesting target in cancer immunotherapy.

Valproate selectively suppresses adolescent anabolic/androgenic steroid-induced aggressive behavior: implications for a role of hypothalamic γ-aminobutyric acid neural signaling.

Pubertal male Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids (AASs) during adolescence (P27-P56) display a highly intense aggressive phenotype that shares many behavioral similarities with pathological aggression in youth. Anticonvulsant drugs like valproate that enhance the activity of the γ-aminobutyric acid (GABA) neural system in the brain have recently gained acceptance as a primary treatment for pathological aggression. This study examined whether valproate would selectively suppress adolescent AAS-induced aggressive behavior and whether GABA neural signaling through GABAA subtype receptors in the latero-anterior hypothalamus (LAH; an area of convergence for developmental and neuroplastic changes that underlie aggression in hamsters) modulate the aggression-suppressing effect of this anticonvulsant medication.

Heart failure impairs the mechanotransduction properties of human cardiac pericytes.

The prominent impact that coronary microcirculation disease (CMD) exerts on heart failure symptoms and prognosis, even in the presence of macrovascular atherosclerosis, has been recently acknowledged. Experimental delivery of pericytes in non-revascularized myocardial infarction improves cardiac function by stimulating angiogenesis and myocardial perfusion. Aim of this work is to verify if pericytes (Pc) residing in ischemic failing human hearts display altered mechano-transduction properties and to assess which alterations of the mechano-sensing machinery are associated with the observed impaired response to mechanical cues.

Cortical ChAT neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner.

The mouse cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT neurons and their synaptic connectivity are unknown. We show that the nearly all cortical ChAT neurons in mice are specialized VIP interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and other VIP/ChAT interneurons.

IL-10-producing B cells are characterized by a specific methylation signature.

Among the family of regulatory B cells, the subset able to produce interleukin-10 (IL-10) is the most studied, yet its biology is still a matter of investigation. The DNA methylation profiling of the il-10 gene locus revealed a novel epigenetic signature characterizing murine B cells ready to respond through IL-10 synthesis: a demethylated region located 4.5 kb from the transcription starting site (TSS), that we named early IL10 regulatory region (eIL10rr).

Extracellular Vesicles: How Drug and Pathology Interfere With Their Biogenesis and Function.

Extracellular vesicles (EV) are at the center of an intense activity of investigation, both for their possible employment as biomarkers of ongoing pathologic processes and for their broad range of biological activities. EV can promote tissue repair in very different pathologic settings, including hindlimb and myocardial ischemia. Importantly, the exact mode of action of EV is still partly understood, since they may act by modulating growth factors and cytokines, signaling pathways, and by transferring non-coding RNAs to target cells.

BET proteins regulate homologous recombination-mediated DNA repair: BRCAness and implications for cancer therapy.

Bromodomain and Extra-Terminal (BET) proteins are historically involved in regulating gene expression and BRD4 was recently found to be involved in DNA damage regulation. Aims of our study were to assess BRD4 regulation in homologous recombination-mediated DNA repair and to explore novel clinical strategies through the combinations of the pharmacological induction of epigenetic BRCAness in BRCA1 wild-type triple negative breast cancer (TNBC) cells by means of BET inhibitors and compounds already available in clinic. Performing a dual approach (chromatin immunoprecipitation and RNA interference), the direct relationship between BRD4 and BRCA1/RAD51 expression was confirmed in TNBC cells.

Assessment of the Mutational Status of NSCLC Using Hypermetabolic Circulating Tumor Cells.

Molecular characterization is currently a key step in NSCLC therapy selection. Circulating tumor cells (CTC) are excellent candidates for downstream analysis, but technology is still lagging behind. In this work, we show that the mutational status of NSCLC can be assessed on hypermetabolic CTC, detected by their increased glucose uptake.

An NF-κB signature predicts low-grade glioma prognosis: a precision medicine approach based on patient-derived stem cells.

Background: While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and representative of the glioma microenvironment.

Methods: By next-generation sequencing, we analyzed the transcriptional profile of GASC derived from patients who underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery.

Functional expression of aryl hydrocarbon receptor on mast cells populating human endometriotic tissues.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The aryl hydrocarbon receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs.