The bad and the good of mesenchymal stem cells in cancer: Boosters of tumor growth and vehicles for targeted delivery of anticancer agents

In cancer biology,mesenchymal stem cells(MSCs)display aspects that can appear contradictory.On one hand,these cells possess several features which give them the ability to specifically target and then sustain cancer cells in their ability to survive the multifaceted host response against cancer.On the other hand,due to this excellent aptitude to home-in on tumor tissues,regardless their location in the host’s body,MSCs are considered to be extremely selective vehicles to reach cancer cells specifically.Recently,MSC sustainment of cancer cell growth is a hot research topic.Indeed,these cells are known to sustain tumor angiogenesis and metastasis formation,to create a microenvironment favorable for cancer cell growth and to down-modulate the immune system capabilities in the host organism.On the other hand,since scientists became able to take advantage of their extremely selective capability to target cancer cells,MSCs are now also thought of in a different light.Indeed,MSCs are now considered a promising vehicle for local expression or delivery of even particularly toxic anticancer agents,ranging from Herpes Simplex Virus to locally-acting antineoplastic drugs.On this basis,investigation is now focused on how to impair the pro-neoplastic features of MSCs on one hand whilst taking advantage of their specific tropism toward cancer cells,on the other.As with the two faces of Janus,this review will concisely explore the research activity in these two apparently conflicting fields.

Targeting Enhancer of Zeste Homolog 2 as a promising strategy for cancer treatment

Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.

Role of exercise in the brain:focus on oligodendrocytes and remyelination

The phrase“Mens sana in corpore sano”taken from Juvenal's Satires(127 a.C.)represents one of the best-known and most used sentences of all time,whose meaning in the modern age refers to the importance of physical activity for mental health and wellbeing.Robust literature demonstrated the positive role of exercise in counteracting several diseases,such as diabetes,cardiovascular diseases,neurodegenerative diseases,cancers and age-related disorders including muscle atrophy,the reduction of aerobic capacity,bone and cartilage loss.

The emerging role of probiotics in neurodegenerative diseases:new hope for Parkinson’s disease?

Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are involved.Altered components of the gut could play a key role in the gut-brain axis,which is a bidirectional system between the central nervous system and the enteric nervous system.Variations in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic,autoimmune,cancer,and,notably,neurodegenerative disorders.Diet can alter the microbiota composition,affecting the gutbrain axis function.Different nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions,including the use of probiotics.Preclinical and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry,modulating different pathways.This review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy,confirming that gut microbiota modulation influences different pro-survival pathways.Future investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.

Novel findings about management of gastric cancer: A summary from 10^(th) IGCC

The Tenth International Gastric Cancer Congress(IGCC) was held in Verona, Italy, from June 19 to 22, 2013. The meeting enclosed various aspects of stomach tumor management, including both tightly clinical approaches, and topics more related to basic research. Moreover, an overview on gastrointestinal stromal tumors was provided too, although here not discussed. Here we will discuss some topics related to molecular biology of gastric cancer(GC), inherent to prognostic, diagnostic and therapeutic tools shown at the conference. Results about well known subjects, such as E-cadherin loss of expression/function, were presented. They revealed that other mutations of the gene were identified, showing a continuous research to improve diagnosis and prognosis of stomach tumor. Simultaneously, new possible molecular markers with an established role for other neoplasms, were discussed, such as mesothelin, stomatin-like protein 2 and Notch-1. Hence, a wide overview including both old and new diagnostic/prognostic tools was offered. Great attention was also dedicated to possible drugs to be used against GC. They included monoclonal antibodies, such as MS57-2.1, drugs used in other pathologies, such as maraviroc, and natural extracts from plants such as biflorin. We would like to contribute to summarize the most impressive studies presented at the IGCC, concerning novel findings about molecular biology of gastric cancer. Although further investigations will be necessary, it can be inferred that more and more tools were developed, so as to better face stomach neoplasms.

Migratory Phenomenons, Bioethics and Vaccinations

The evolution of the HIV following migratory phenomenons is reported in an interesting study carried on for 15 years. Polymerase Chain Reaction (PCR) is a technique in molecular biology that amplifies a specific region of deoxyribonucleic acid (DNA), and has been useful in the molecular characterization of viruses as poxviruses. In many countries, such as?Italy,the vaccinations are included in the so-called sanitary obliged not coercive treatments. This means that the obligation is anticipated for all the subjects belonging to one determined range of age to undergo some vaccinations, but these are not subministrated by force in case of refusal. The legitimacy of the obligatory vaccination against the smallpox, with all the risks connected,?stated that such “risks were too much reduced to be seriously taken in consideration for the benefits produced on the collectivity”.?To ratify this obligation brings, however, to the reimbursement of the?incidental?damages produced by the vaccination. Nevertheless, mass vaccination against smallpox continues to be a leading initiative in western countries to guard against bioterrorist attack.

Molecular network of neuronal autophagy in the pathophysiology and treatment of depression

Major depressive disorder （MDD） is a complicated multifactorial induced disease, characterized by depressed mood, anhedonia, fatigue, and altered cognitive function. Recently, many studies have shown that antidepressants regulate autophagy. In fact, autophagy, a conserved lysosomal degradation pathway, is essential for the central nervous system. Dysregulation of autophagic pathways, such as the mammalian target of rapamycin （mTOR） signaling pathway and the beclin pathway, has been studied in neurodegenerative diseases. However, autophagy in MDD has not been fully studied. Here, we discuss whether the dysregulation of autophagy contributes to the pathophysiology and treatment of MDD and summarize the current evidence that shows the involvement of autophagy in MDD.