Palmiro Poltronieri

This descriptive review summarizes the most recent findings on the induction and distribution of viable non-culturable (VBNC) Listeria monocytogenes in food production conditions and food. The aim was to obtain information on the factors that favor the transition to the VBNC state in L. monocytogenes; its resuscitation capacity; and, according to scientific articles published since 2020, how food contamination by the bacterium in a VBNC state can be prevented. The methods used for VBNC L. monocytogenes detection were also reviewed. A few studies reported the presence of VBNC L. monocytogenes in food, in which fresh produce and chicken meat were considered. Different physicochemical stresses such as exposure to disinfectants with diverse actions and essential oils, desiccation, low temperatures, absence of nutrients, high NaCl and iron concentrations, and low pH adjusted with acetic acid were reported to induce the VBNC state in L. monocytogenes. The VBNC forms of L. monocytogenes were able to regain growth and virulence. This could pose a safety risk that cannot be revealed by the standard culture-dependent methods recommended for L. monocytogenes detection. Therefore, the presence in food and food production plants of VBNC L. monocytogenes should be prevented by the appropriate use of hurdles and cleaning/disinfection procedures. The opportunity to harmonize VBNC cell detection methods for regular use in food safety evaluation also emerged.

This descriptive review summarizes the most recent findings on the induction and distribution of viable non-culturable (VBNC) Listeria monocytogenes in food production conditions and food. The aim was to obtain information on the factors that favor the transition to the VBNC state in L. monocytogenes, its resuscitation capacity, and, according to scientific articles published since 2020, how food contamination by the bacterium in VBNC state can be prevented. The methods used for VBNC L. monocytogenes detection were also reviewed. A few studies reported the presence of VBNC L. monocytogenes in food, in which fresh produce and chicken meat were considered. Different physicochemical stresses such as exposure to disinfectants with diverse actions and essential oils, desiccation, low temperatures, absence of nutrients, high NaCl and iron concentrations, and low pH adjusted with acetic acid were reported to induce the VBNC state in L. monocytogenes. The VBNC forms of L. monocytogenes were able to regain growth and virulence. This could pose a safety risk that cannot be revealed by the standard culture-dependent methods recommended for L. mono-cytogenes detection. Therefore, the presence in food and food production plants of VBNC L. mon-ocytogenes should be prevented by appropriate use of hurdles and cleaning/disinfection proce-dures. The opportunity to harmonize VBNC cell detection methods for regular use in food safety evaluation also emerged.

Biomolecular condensates (BCs), RNA–protein complexes, have emerged as potential therapeutic targets for various cellular pathologies, including cancer. The mechanisms underlying liquid–liquid phase separation rely on the properties of proteins with intrinsically disordered regions and prion-like domains, which drive phase separation in conjunction with their RNA partners. These ribonucleoprotein complexes are distinct in their localization, compartmentalization, epigenetic regulation, and dynamics. BCs are categorized as either nuclear—such as promyelocytic leukemia nuclear bodies, speckles, paraspeckles, and Cajal bodies—or cytosolic, including stress granules (SGs), P bodies, and U bodies. Regulatory RNAs, assembled with protein partners through phase separation, exhibit oncogenic properties and perform key biological functions, including gene transcription, euchromatin/heterochromatin formation, mRNA splicing, mRNA translation, protein compartmentalization, and degradation. Epitranscriptome-modifying enzymes regulate the stability and oncogenic potential of noncoding RNAs (ncRNAs). These RNAs, along with their associated epitranscriptomic and protein modifications, play critical roles in the functioning and dissolution of condensates. Recent advancements in cancer therapy have focused on developing drugs targeting the epitranscriptomic machinery, including the writers, readers, and erasers of RNA modifications. Therapeutic strategies aim to target oncogenic RNAs, tumor-promoting proteins, and RNA–protein interaction domains. Several cancer therapeutic compounds have been developed using the PROTAC and RIBOTAC approaches. Moreover, small molecules targeting protein–RNA interactions and antisense oligonucleotides have been developed. Promising avenues in cancer therapeutics involve the inhibition of ncRNAs and their associated protein complexes, modulation of BCs, regulation of SGs and paraspeckles, and development of small molecule compounds with potential applications across various cancer types.

Biomolecular condensates (BCs), including membraneless organelles, are basically Ribonucleic acid (RNA)-protein complexes that are emerging as a potential candidate because of its paramount significance in revealing fundamentals of cell biology and pathology including cancer. Aiming to understand its importance, scientists are dealing with it in an interdisciplinary manner—from polymer chemistry to genetics. Over time the mechanism of liquid-liquid phase separation (LLPS) and the model of ‘Stickers and Spacers’ have widened our understanding and broadened our scope of approaches to get insights into these molecular entities. RNA molecules and its specific partner proteins, certain ribonucleoproteins (RNPs), play pivotal roles in different trajectories of BCs, i.e., in localization, compartmentalization, epigenetic regulation, and dynamics. However, several aspects need to be made clearer to tackle human diseases including cancer. In addition to the RNAs, in this review specific aspects of the BCs are presented in the context of neurodegenerative diseases, viral infections and cancer, and their link with stress granules (SG), P bodies, paraspeckles, and host encoded and viral encoded non-coding RNAs, discussing cancer associated proteins, tumour suppressors and repressors, dysregulation of cancer signals, and role of super enhancers. A special focus is reserved to oncolytic viruses and epidemic viruses, through the intervention on stress granule protein partners, virus-formed intracellular condensates, and viral RNAs. The review covers not only the basics of BCs but also encompasses the emerging context of condensate-targeted drug discovery and cancer therapeutics by means of Proteolysis-targeting chimera (PROTAC), Ribonuclease-targeting chimera (RIBOTAC), small molecule inhibitors of protein-RNA interactions, Antisense oligonucleotides (ASO) and compounds targeting non-coding RNA (ncRNA) triple helix, determining RNA degradation.

Recently, new data have been added to the interaction between non-coding RNAs (ncRNAs) and epigenetic machinery. Epigenetics includes enzymes involved in DNA methylation, histone modifications, and RNA modifications, and mechanisms underlying chromatin structure, repressive states, and active states operating in transcription. The main focus is on long ncRNAs (lncRNAs) acting as scaffolds to assemble protein complexes. This review does not cover RNA’s role in sponging microRNAs, or decoy functions. Several lncRNAs were shown to regulate chromatin activation and repression by interacting with Polycomb repressive complexes and mixed-lineage leukemia (MLL) activating complexes. Various groups reported on enhancer of zeste homolog 2 (EZH2) interactions with regulatory RNAs. Knowledge of the function of these complexes opens the perspective to develop new therapeutics for cancer treatment. Lastly, the interplay between lncRNAs and epitranscriptomic modifications in cancers paves the way for new targets in cancer therapy. The approach to inhibit lncRNAs interaction with protein complexes and perspective to regulate epitrascriptomics-regulated RNAs may bring new compounds as therapeuticals in various types of cancer.

Editorial: Latest perspective on microbes detection: from laboratory to on-spot sensor

Neuroprotection is one of the hot topics in medicine. Alzheimer’s disease, amyotrophic lateral sclerosis, retinal pigment epithelial (RPE) degeneration, and axonal degeneration have been studied for the involvement of NAD depletion. Localized NAD+ depletion could lead to overactivation and crowding of local NAD+ salvage pathways. It has been stated that NAD+ depletion caused by PARPs and PAR cycling has been related to metabolic diseases and cancer. Additionally, it is now acknowledged that SARM1 dependent NAD+ depletion causes axon degeneration. New targeted therapeutics, such as SARM1 inhibitors, and NAD+ salvage drugs will help alleviate the dysfunctions affecting cell life and death in neurodegeneration as well as in metabolic diseases and cancer.

Ventricina del Vastese is a traditional dry fermented sausage from Central Italy not yet characterized for the occurrence, identity and safety of coagulase-negative staphylococci (CNS), a bacterial group technologically important for this kind of product. Therefore, in this study, 98 CNS isolates from four manufacturers were differentiated using repetitive element palindromic PCR (Rep-PCR) and identified using 16S rRNA gene sequencing. These were examined for genes encoding biogenic amine (BA) production, resistance to aminoglycosides, β-lactams, tetracyclines and staphylococcal enterotoxins (SEs). Staphylococcus succinus (55%) predominated, followed by S. xylosus (30%), S. epidermidis (7.4%), S. equorum (3.1%), S. saprophyticus (3.1%) and S. warneri (1%). One S. succinus subsp. casei isolate was slightly β-hemolytic. SEs and the histidine decarboxylase gene hdcA were not detected, whereas the tyrosine decarboxylase gene tdcA was detected in four S. xylosus isolates. The blaZ beta-lactamase gene in an S. equorum isolate, tetracycline resistance genes tetK in six S. succinus isolates and tetA in one S. succinus isolate also bearing tetK were found. The product examined is characterized by a peculiar CNS species ratio and a low occurrence and diversity of AR transferable genes than found in other studies, as a probable consequence of production only with meat from animals raised in small farms with extensive rearing systems in which antibiotic usage is infrequent.