Cancer is a multifactorial pathology and it represents the second leading cause of death worldwide. In the recent years, numerous studies highlighted the dual role of the gut microbiota in preserving host’s health. Gut resident bacteria are able to produce a number of metabolites and bioproducts necessary to protect host’s and gut’s homeostasis. Conversely, several microbiota subpopulations may expand during pathological dysbiosis and therefore produce high levels of toxins capable, in turn, to trigger both inflammation and tumorigenesis. Importantly, gut microbiota can interact with the host either modulating directly the gut epithelium or the immune system. Numerous gut populating bacteria, called probiotics, have been identified as protective against the genesis of tumors. Given their capability of preserving gut homeostasis, probiotics are currently tested to help to fight dysbiosis in cancer patients subjected to chemotherapy and radiotherapy. Most recently, three independent studies show that specific gut resident species may potentiate the positive outcome of anti-cancer immunotherapy. The highly significant studies, uncovering the tight association between gut microbiota and tumorigenesis, as well as gut microbiota and anti-cancer therapy, are here described. The role of the Lactobacillus rhamnosus GG (LGG), as the most studied probiotic model in cancer, is also reported. Overall, according to the findings here summarized, novel strategies integrating probiotics, such as LGG, with conventional anti-cancer therapies are strongly encouraged.

Parkinson’s disease (PD) is the most prevalent central nervous system (CNS) movement disorder and the second most common neurodegenerative disease overall. PD is characterized by the progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) within the midbrain, accumulation of alpha-synuclein (α-SYN) in Lewy bodies and neurites and excessive neuroinflammation. The neurodegenerative processes typically begin decades before the appearance of clinical symptoms. Therefore, the diagnosis is achievable only when the majority of the relevant DAergic neurons have already died and for that reason available treatments are only palliative at best. The causes and mechanism(s) of this devastating disease are ill-defined but complex interactions between genetic susceptibility and environmental factors are considered major contributors to the etiology of PD. In addition to the role of classical gene mutations in PD, the importance of regulatory elements modulating gene expression has been increasingly recognized. One example is the critical role played by microRNAs (miRNAs) in the development and homeostasis of distinct populations of neurons within the CNS and, in particular, in the context of PD. Recent reports demonstrate how distinct miRNAs are involved in the regulation of PD genes, whereas profiling approaches are unveiling variations in the abundance of certain miRNAs possibly relevant either to the onset or to the progression of the disease. In this review, we provide an overview of the miRNAs recently found to be implicated in PD etiology, with particular focus on their potential relevance as PD biomarkers, as well as their possible use in PD targeted therapy.

Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD) physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA) neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors. Notably, with age, microglia may adopt a potent neurotoxic, pro-inflammatory “primed” (M1) phenotype when challenged with inflammatory or neurotoxic stimuli that hamper brain's own restorative potential and inhibit endogenous neurorepair mechanisms. In the last decade we have provided evidence for a major role of microglial crosstalk with astrocytes, mDA neurons and neural stem progenitor cells (NSCs) in the MPTP- (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-) mouse model of PD, and identified Wnt/β-catenin signaling, a pivotal morphogen for mDA neurodevelopment, neuroprotection, and neuroinflammatory modulation, as a critical actor in glia-neuron and glia-NSCs crosstalk. With age however, Wnt signaling and glia-NSC-neuron crosstalk become dysfunctional with harmful consequences for mDA neuron plasticity and repair. These findings are of importance given the deregulation of Wnt signaling in PD and the emerging link between most PD related genes, Wnt signaling and inflammation. Especially, in light of the expanding field of microRNAs and inflammatory PD-related genes as modulators of microglial-proinflammatory status, uncovering the complex molecular circuitry linking PD and neuroinflammation will permit the identification of new druggable targets for the cure of the disease. Here we summarize recent findings unveiling major microglial inflammatory and oxidative stress pathways converging in the regulation of Wnt/β-catenin signaling, and reciprocally, the ability of Wnt signaling pathways to modulate microglial activation in PD. Unraveling the key factors and conditons promoting the switch of the proinflammatory M1 microglia status into a neuroprotective and regenerative M2 phenotype will have important consequences for neuroimmune interactions and neuronal outcome under inflammatory and/or neurodegenerative conditions.

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.

Export of mRNA from the nucleus is linked to proper processing and packaging into ribonucleoprotein complexes. Although several observations indicate a coupling between mRNA 3 end formation and export, it is not known how these two processes are mechanistically connected. Here, we show that a subunit of the mammalian pre-mRNA 3 end processing complex, CF I m 68, stimulates mRNA export. CF I m 68 shuttles between the nucleus and the cytoplasm in a transcription-dependent manner and interacts with the mRNA export receptor NXF1/TAP. Consistent with the idea that CF I m 68 may act as a novel adaptor for NXF1/TAP, we show that CF I m 68 promotes the export of a reporter mRNA as well as of endogenous mRNAs, whereas silencing by RNAi results in the accumulation of mRNAs in the nucleus. Moreover, CF I m 68 associates with 80S ribosomes but not polysomes, suggesting that it is part of the mRNP that is remodeled in the cytoplasm during the initial stages of translation. These results reveal a novel function for the pre-mRNA 3 end processing factor CF I m 68 in mRNA export. INTRODUCTIONThe removal of introns by splicing as well as cleavage and polyadenylation at the 3Ј end of RNA polymerase II primary transcripts (pre-mRNAs) are usually required before they can be exported from the nucleus as mature mRNAs (Erkmann and Kutay, 2004). This observation has suggested that transport factors interact with the RNA during premRNA processing. Indeed, recent discoveries have lent support to this hypothesis. The splicing reaction deposits on the mRNA a specific subset of proteins called the exon junction complex (EJC, for review see Tange et al., 2004). REF, a component of the EJC, facilitates mRNA export by interacting with the mRNA export factor NXF1 (also called TAP, for review, see Reed and Hurt, 2002). NXF1 was originally identified as the export receptor for type D retroviral RNAs that associate with NXF1 through a sequence-specific interaction with the constitutive transport element (CTE). However, NXF1 recruitment on cellular mRNAs requires adaptor proteins such as Aly/REF (hereafter named REF). In yeast Mex67 (the homolog of NXF1) is recruited by Yra1 (homolog of REF), which is also essential for the export of poly(A) RNA in Saccharomyces cerevisiae. In contrast in metazoans, REF is dispensable for bulk mRNA export. This raises the possibility that multiple and partially redundant adaptor proteins may be responsible for the recruitment of NXF1. Indeed, spliceosomal proteins, including U2AF35 (Zolotukhin et al., 2002) and some members of the SR family of splicing factors, were shown to interact with NXF1 and act as adaptors for NXF1-dependent export of poly(A) mRNAs (Huang and Steitz, 2001;Huang et al., 2003;Lai and Tarn, 2004;Hargous et al., 2006;Tintaru et al., 2007).Several observations have linked 3Ј end cleavage and polyadenylation to mRNA export (for review see Zhao et al., 1999). For example, RNA polymerase II reporter transcripts lacking a polyadenylation signal are retained in the nucleus of yeast cells. Positioning a...