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.

There is recent evidence to indicate the existence of an inverse association between the incidence of neurological disorders and cancer development. Concurrently, the transcriptional pathways responsible for the onset of glioblastoma multiforme (GBM) and Alzheimer's disease (AD) have been found to be mutually exclusive between the two pathologies. Despite advancements being made concerning the knowledge of the molecular mechanisms responsible for the development of GBM and AD, little is known about the identity of the microRNA (miRNAs or miRs) involved in the development and progression of these two pathologies and their possible inverse expression patterns. On these bases, the aim of the present study was to identify a set of miRNAs significantly de‑regulated in both GBM and AD, and hence to determine whether the identified miRNAs exhibit an inverse association within the two pathologies. For this purpose, miRNA expression profiling datasets derived from the Gene Expression Omnibus (GEO) DataSets and relative to GBM and AD were used. Once the miRNAs significantly de‑regulated in both pathologies were identified, DIANA‑mirPath pathway prediction and STRING Gene Ontology enrichment analyses were performed to establish their functional roles in each of the pathologies. The results allowed the identification of a set of miRNAs found de‑regulated in both GBM and AD, whose expression levels were inversely associated in the two pathologies. In particular, a strong negative association was observed between the expression levels of miRNAs in GBM compared to AD, suggesting that although the molecular pathways behind the development of these two pathologies are the same, they appear to be inversely regulated by miRNAs. Despite the identification of this set of miRNAs which may be used for diagnostic, prognostic and therapeutic purposes, further functional in vitro and in vivo evaluations are warranted in order to validate the diagnostic and therapeutic potential of the identified miRNAs, as well as their involvement in the development of GBM and AD.

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.

The severe acute respiratory syndrome associated coronavirus‑2 (SARS‑CoV‑2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID‑19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off‑label for the treatment of COVID‑19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune‑checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death‑1 (PD‑1)/PD ligand-1 (PD‑L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID‑19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T‑cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti‑tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T‑cell exhaustion, which is also observed following SARS‑CoV‑2 infection. Importantly, when treated with anti‑PD‑1 and anti‑PD‑L1 antibodies, they restore their T‑cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti‑PD‑1 antibody administration to both cancer and non‑cancer individuals affected by COVID‑19. The results may prove the hypothesis that restoring exhausted T‑cells may be a winning strategy to beat SARS‑CoV‑2 infection.