Identifying appropriate preclinical cancer models remains a major challenge in increasing the efficiency of drug development. A potential strategy to improve patient outcomes could be selecting the ‘right’ treatment in preclinical studies performed in patient-derived xenografts (PDXs) obtained by direct implants of surgically resected tumours in mice. These models maintain morphological similarities and recapitulate molecular profiling of the original tumours, thus representing a useful tool in evaluating anticancer drug response. In this review, we will present the state-of-art use of PDXs as a reliable strategy to predict clinical findings. The main advantages and limitations will also be discussed.

Aging is a multi-faceted process caused by the accumulation of cellular damage over time, associated with a gradual reduction of physiological activities in cells and organs. This degeneration results in a reduced ability to adapt to homeostasis perturbations and an increased incidence of illnesses such as cognitive decline, neurodegenerative and cardiovascular diseases, cancer, diabetes, and skeletal muscle pathologies. Key features of aging include a chronic low-grade inflammation state and a decrease of the autophagic process. The Mediterranean diet has been associated with longevity and ability to counteract the onset of age-related disorders. Extra virgin olive oil, a fundamental component of this diet, contains bioactive polyphenolic compounds as hydroxytyrosol (HTyr) and oleuropein (OLE), known for their antioxidant, anti-inflammatory, and neuroprotective properties. This review is focused on brain, skeletal muscle, and gut microbiota, as these systems are known to interact at several levels. After the description of the chemistry and pharmacokinetics of HTyr and OLE, we summarize studies reporting their effects in in vivo and in vitro models of neurodegenerative diseases of the central/peripheral nervous system, adult neurogenesis and depression, senescence and lifespan, and age-related skeletal muscle disorders, as well as their impact on the composition of the gut microbiota.

Resistance conferred by biotrophic pathogens often requires salicylic acid (SA) signaling, whereas necrotrophic pathogens or wounding mainly activate the jasmonate/ethylene (JA/ET)-dependent pathway. Crosstalk connections between these two independent signaling pathways may lead to synergistic or antagonistic behavior. In order to shed some light on the crosstalk between these two hormones in Arabidopsis plants, a proteomic approach combined with a transcriptomic analysis has been used to identify molecules differentially expressed upon single or simultaneous treatment with both phytohormones. Twenty-five nonredundant differential proteins were revealed upon treatment with SA or JA alone or in combination, which are involved in general metabolic processes as well as in response to stress, in developmental processes, in protein metabolism and transport. Interestingly, gene expression study, carried out on genes involved in oxidative stress and in biotic and/or abiotic stress, highlighted the correspondence between proteomic and transcriptomic approaches, performed here by RT-PCR. Our data clearly demonstrate that almost all genes/proteins involved in oxidative stress as well as in biotic and/or abiotic stress are mainly induced upon JA treatment and only a few of them are overexpressed upon SA treatment. Moreover, we found that a substantially negative crosstalk is established upon the combined action of the two hormones and that generally SA exerts a negative crosstalk compared to the JA pathway. Our study corroborates the hypothesis that the combination of both phytohormones induces reprogramming of the plant transcriptome, but at the same time highlights the presence of a complex network of signaling that is far to be completely elucidated.

In plant defense, priming is a physiological process by which a plant prepares to more quickly or aggressively respond to a future biotic or abiotic stress. This unique physiological state can be induced by beneficial microbes or by treatment with natural or synthetic compounds. Priming has been described copiously, mainly in dicots, but the study on the molecular mechanisms regulating the phenomenon is still at its infancy. A fascinating possibility is that epigenetic changes may be the main actors on priming establishment. A more accessible chromatin structure, due to DNA methylation and/or histone modifications, could facilitate a quicker and more potent gene response to a subsequent attack. Here, we investigated the impact of methyl jasmonate (MeJA)-induced priming on the response efficacy to mechanical wounding of a monocot (Oryza sativa). In particular, we showed that MeJA primes plants for increased expression of defense-related genes, such as OsBBPI and OsPOX, upon wounding. Finally, we provided evidence that MeJA modulates histone modifications in the promoter region of OsBBPI, as well as changes at genome-wide DNA methylation level. Together these studies corroborate the importance of priming in strengthening plant defense and support the growing evidence that epigenetic regulation plays a pivotal role in priming onset.

The role of jasmonates in defense priming has been widely recognized. Priming is a physiological process by which a plant exposed to low doses of biotic or abiotic elicitors activates faster and/or stronger defense responses when subsequently challenged by a stress. In this work, we investigated the impact of MeJA-induced defense responses to mechanical wounding in rice (Oryza sativa). The proteome reprogramming of plants treated with MeJA, wounding or MeJA+wounding has been in-depth analyzed by using a combination of high throughput profiling techniques and bioinformatics tools. Gene Ontology analysis identified protein classes as defense/immunity proteins, hydrolases and oxidoreductases differentially enriched by the three treatments, although with different amplitude. Remarkably, proteins involved in photosynthesis or oxidative stress were significantly affected upon wounding in MeJA-primed plants. Although these identified proteins had been previously shown to play a role in defense responses, our study revealed that they are specifically associated with MeJA-priming. Additionally, we also showed that at the phenotypic level MeJA protects plants from oxidative stress and photosynthetic damage induced by wounding. Taken together, our results add novel insight into the molecular actors and physiological mechanisms orchestrated by MeJA in enhancing rice plants defenses after wounding.