Recently it was discovered that a transient activation of transcription factor NF-κB can give cells properties essential for invasiveness and cancer initiating potential. In contrast, most oncogenes to date were characterized on the basis of mutations or by their constitutive overexpression. Study of NF-κB actually leads to a far more dynamic perspective on cancer: tumors caused by diverse oncogenes apparently evolve into cancer after loss of feedback regulation for NF-κB. This event alters the cellular phenotype and the expression of hormonal mediators, modifying signals between diverse cell types in a tissue. The result is a disruption of stem cell hierarchy in the tissue, and pervasive changes in the microenvironment and immune response to the malignant cells.

Taurine is a fundamental mediator of homeostasis that exerts multiple roles to confer protection against oxidant stress. The development of hypertension, muscle/neuroassociated disorders, hepatic cirrhosis, cardiac dysfunction and ischemia/reperfusion are examples of some injuries that are linked with oxidative stress. The present review gives a comprehensive description of all the underlying mechanisms of taurine, with the aim to explain its anti-oxidant actions. Taurine is regarded as a cytoprotective molecule due to its ability to sustain normal electron transport chain, maintain glutathione stores, upregulate anti-oxidant responses, increase membrane stability, eliminate inflammation and prevent calcium accumulation. In parallel, the synergistic effect of taurine with other potential therapeutic modalities in multiple disorders are highlighted. Apart from the results derived from research findings, the current review bridges the gap between bench and bedside, providing mechanistic insights into the biological activity of taurine that supports its potential therapeutic efficacy in clinic. In the future, further clinical studies are required to support the ameliorative effect of taurine against oxidative stress. Contents1. Introduction 2. The role of taurine in homeostasis 3. The role of taurine against oxidative stress and its underlying molecular mechanisms 4. The beneficial effect of taurine against neuro-associated disorders 5. The anti-oxidant efficacy of taurine against cardiacassociated oxidative stress 6. The regulatory importance of taurine in ischemia and reperfusion 7. The anti-oxidant efficacy of taurine against muscle-associated disorders 8. The anti-oxidant efficacy of taurine against hepatic-associated stress 9. The anti-oxidant properties of taurine in various toxicmediated insults 10. Conclusions

One of the fundamental discoveries in the field of biology is the ability to modulate the genome and to monitor the functional outputs derived from genomic alterations. In order to unravel new therapeutic options, scientists had initially focused on inducing genetic alterations in primary cells, in established cancer cell lines and mouse models using either RNA interference or cDNA overexpression or various programmable nucleases [zinc finger nucleases (ZNF), transcription activator-like effector nucleases (TALEN)]. Even though a huge volume of data was produced, its use was neither cheap nor accurate. Therefore, the clustered regularly interspaced short palindromic repeats (CRISPR) system was evidenced to be the next step in genome engineering tools. CRISPR-associated protein 9 (Cas9)-mediated genetic perturbation is simple, precise and highly efficient, empowering researchers to apply this method to immortalized cancerous cell lines, primary cells derived from mouse and human origins, xenografts, induced pluripotent stem cells, organoid cultures, as well as the generation of genetically engineered animal models. In this review, we assess the development of the CRISPR system and its therapeutic applications to a wide range of complex diseases (particularly distinct tumors), aiming at personalized therapy. Special emphasis is given to organoids and CRISPR screens in the design of innovative therapeutic approaches. Overall, the CRISPR system is regarded as an eminent genome engineering tool in therapeutics. We envision a new era in cancer biology during which the CRISPR-based genome engineering toolbox will serve as the fundamental conduit between the bench and the bedside; nonetheless, certain obstacles need to be addressed, such as the eradication of side-effects, maximization of efficiency, the assurance of delivery and the elimination of immunogenicity.

No abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with associated malaise, headaches, sleep disturbance, and cognitive impairment, which severely impacts quality of life. A significant percentage of ME/CFS patients remain undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers. ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown, preventing the development of effective treatments. The ME/CFS phenotype has been associated with abnormalities in energy metabolism, which are apparently due to mitochondrial dysfunction in the absence of mitochondrial diseases, resulting in reduced oxidative metabolism. Such mitochondria may be further contributing to the ME/CFS symptomatology by extracellular secretion of mitochondrial DNA, which could act as an innate pathogen and create an autoinflammatory state in the hypothalamus. We propose that stimulation of hypothalamic mast cells by environmental, neuroimmune, pathogenic and stress triggers activates microglia, leading to focal inflammation in the brain and disturbed homeostasis. This process could be targeted for the development of novel effective treatments.