From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy.

In the past decades, Chimeric Antigen Receptor (CAR)-T cell therapy has achieved remarkable success, leading to the approval of six therapeutic products for haematological malignancies. Recently, the therapeutic potential of this therapy has also been demonstrated in non-tumoral diseases. Currently, the manufacturing process to produce clinical-grade CAR-T cells is complex, time-consuming, and highly expensive.

RNA Editing in Cancer Progression.

Coding and noncoding RNA molecules play their roles in ensuring cell function and tissue homeostasis in an ordered and systematic fashion. RNA chemical modifications can occur both at bases and ribose sugar, and, similarly to DNA and histone modifications, can be written, erased, and recognized by the corresponding enzymes, thus modulating RNA activities and fine-tuning gene expression programs. RNA editing is one of the most prevalent and abundant forms of post-transcriptional RNA modification in normal physiological processes.

IL-1α and IL-36 Family Cytokines Can Undergo Processing and Activation by Diverse Allergen-Associated Proteases.

Inflammation driven by environmental allergens is an important source of morbidity in diseases such as asthma and eczema. How common allergens promote inflammation is still poorly understood, but previous studies have implicated the protease activity associated with many allergens as an important component of the pro-inflammatory properties of these agents. The IL-1 family cytokine, IL-33, has recently been shown to undergo processing and activation by proteases associated with multiple common allergens.

IL-1 family cytokines serve as 'activity recognition receptors' for aberrant protease activity indicative of danger.

Members of the extended IL-1 cytokine family play key roles as instigators of inflammation in numerous infectious and sterile injury contexts and are highly enriched at barrier surfaces such as the skin, lungs and intestinal mucosa. Because IL-1 family cytokines do not possess conventional ER-golgi trafficking and secretory signals, these cytokines are typically released into the extracellular space due to tissue damage resulting in necrosis, or pathogen detection resulting in pyroptosis. The latter feature, in combination with other factors, suggests that IL-1 family cytokines serve as canonical damage-associated molecular patterns (DAMPs), which instigate inflammation in response to tissue damage.

DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells.

Vaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in many cancer types and its correlation with poor prognosis has been determined, showing VRK1 as a new therapeutic target in oncology. Using in vitro selection, high-affinity DNA aptamers to VRK1 were selected from a library of ssDNA.

The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells.

The role of Src family kinases (SFKs) in human tumors has been always associated with tyrosine kinase activity and much less attention has been given to the SH2 and SH3 adapter domains. Here, we studied the role of the c-Src-SH2 domain in triple-negative breast cancer (TNBC). To this end, SUM159PT and MDA-MB-231 human cell lines were employed as model systems.

DNA aptamers targeting Leishmania infantum H3 protein as potential diagnostic tools.

Leishmaniasis is a disease caused by a parasite of the genus Leishmania that affects millions of people worldwide. These parasites are characterized by the presence of a DNA-containing granule, the kinetoplastid, located in the single mitochondrion at the base of the cell's flagellum. Interestingly, these flagellates do not condense chromatin during mitosis, possibly due to the specific molecular features of their histones.

Dissecting the transcriptional regulatory networks of promoter-associated noncoding RNAs in development and cancer.

In-depth analysis of global RNA sequencing has enabled a comprehensive overview of cellular transcriptomes and revealed the pervasive transcription of divergent RNAs from promoter regions across eukaryotic genomes. These studies disclosed that genomes encode a vast repertoire of RNAs beyond the well-known protein-coding messenger RNAs. Furthermore, they have provided novel insights into the regulation of eukaryotic epigenomes, and transcriptomes, including the identification of novel classes of noncoding transcripts, such as the promoter-associated noncoding RNAs (pancRNAs).

ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma.

Accumulating evidence has proved that deregulation of ΔNp63 expression plays an oncogenic role in head and neck squamous cell carcinomas (HNSCCs). Besides p63, the type 1-insulin-like growth factor (IGF) signalling pathway has been implicated in HNSCC development and progression. Most insulin/IGF1 signalling converges intracellularly onto the protein adaptor insulin receptor substrate-1 (IRS-1) that transmits signals from the receptor to downstream effectors, including the PI3K/AKT and the MAPK kinase pathways, which, ultimately, promote proliferation, invasion, and cell survival.

Spiculosiphon oceana (Foraminifera) a new bio-indicator of acidic environments related to fluid emissions of the Zannone Hydrothermal Field (central Tyrrhenian Sea).

The new record of a shallow-water submarine hydrothermal field (<150 m w.d.) in the western Mediterranean Sea (Tyrrhenian Sea, Italy) allows us to study CO fluid impact on benthic foraminifers.

p63 Sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling.

The predominant p63 isoform, ΔNp63, is a master regulator of normal epithelial stem cell (SC) maintenance. However, in vivo evidence of the regulation of cancer stem cell (CSC) properties by p63 is still limited. Here, we exploit the transgenic MMTV-ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) mouse model of carcinogenesis to dissect the role of p63 in the regulation of mammary CSC self-renewal and breast tumorigenesis.

Caspase 3 in molluscan tissues: localization and possible function.

The presence and localization of caspase 3, a master enzyme in apoptosis, have been analyzed in tissues of four species of Molluscs: the Bivalves Callista chione and Adamussium colbecki and the Gastropods Helix pomatia and Neobuccinum eatoni. Western blotting and immunocytochemical analyses show that a 32 kDa caspase 3 is present in guts, in gill lamellae and in digestive glands during digestion but not in heart tissue or in resting digestive glands. The enzyme is also found in gonads of both sexes but there are significant differences between Bivalves and Gastropods and between male and female germ cells, especially in late stages of differentiation.

Benthic foraminifera from two coastal lakes of southern Latium (Italy). Preliminary evaluation of environmental quality.

Benthic foraminifera and sediment texture were studied on a total of 37 samples, collected from two brackish-water coastal basins: Fogliano Lake and Lungo Lake (central Italy). The research was performed as a preliminary low-cost survey to highlight the degree of the environmental stress and to recognize a possible anthropogenic disturbance. The sedimentological and foraminiferal data were processed by bivariate and multivariate statistical analysis.

Oogenesis at subzero temperatures: a comparative study of the oocyte morphology in nine species of Notothenioids.

Oogenesis was examined in nine species of Antarctic fish to verify the existence of morphological peculiarities. The analyses were carried out on specimens belonging to three different families of Notothenioids (Nototheniidae, Channichthyidae and Bathydraconidae), all captured in the Ross Sea, in front of the Italian Station of Terra Nova Bay. Following dissection, the ovaries were processed and examined at the light and electron microscopes to determine the oocyte gross and fine morphology.