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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.

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

Taurine (2-aminoethanesulfonic acid) contributes to homeostasis, mainly through its antioxidant and osmoregulatory properties. Taurine's influx and efflux are mainly mediated through the ubiquitous expression of the sodium/chloride-dependent taurine transporter, located on the plasma membrane. The significance of the taurine transporter has been shown in various organ malfunctions in taurine-transporter-null mice. The taurine transporter differentially responds to various cellular stimuli including ionic environment, electrochemical charge, and pH changes. The renal system has been used as a model to evaluate the factors that significantly determine the regulation of taurine transporter regulation. Contents 1. Taurine synthesis 2. Taurine transport 3. regulation of TauT transporter 4. Volume-insensitive and-sensitive taurine transport 5. Taurine deficient conditions 6. Taurine Transporter deficient mice (TauT KO) 7. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MelaS) syndrome 8. conclusions

The structure of synthetic mRNAs as used in vaccination against cancer and infectious diseases contain specifically designed caps followed by sequences of the 5′ untranslated repeats of β-globin gene. The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins. However, the cellular homeostasis is finely balanced and obeys to specific laws of thermodynamics conferring balance between complexity and growth rate in evolution. An overwhelming and forced translation even under alarming conditions of the cell during a concurrent viral infection, or when molecular pathways are trying to circumvent precursor events that lead to autoimmunity and cancer, may cause the recipient cells to ignore their differential sensitivities which are essential for keeping normal conditions. The elF4E which is a powerful RNA regulon and a potent oncogene governing cell cycle progression and proliferation at a post-transcriptional level, may then be a great contributor to disease development. The mechanistic target of rapamycin (mTOR) axis manly inhibits the elF4E to proceed with mRNA translation but disturbance in fine balances between mTOR and elF4E action may provide a premature step towards oncogenesis, ignite pre-causal mechanisms of immune deregulation and cause maturation (aging) defects.

The mRNA SARS-CoV-2 vaccines were brought to market in response to the widely perceived public health crises of Covid-19. The utilization of mRNA vaccines in the context of infectious disease had no precedent, but desperate times seemed to call for desperate measures. The mRNA vaccines utilize genetically modified mRNA encoding spike proteins. These alterations hide the mRNA from cellular defenses, promote a longer biological half-life for the proteins, and provoke higher overall spike protein production. However, both experimental and observational evidence reveals a very different immune response to the vaccines compared to the response to infection with SARS-CoV-2. As we will show, the genetic modifications introduced by the vaccine are likely the source of these differential responses. In this paper, we present the evidence that vaccination, unlike natural infection, induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. We explain the mechanism by which immune cells release into the circulation large quantities of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances are shown to have a potentially direct causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell’s palsy, liver disease, impaired adaptive immunity, increased tumorigenesis, and DNA damage. We show evidence from adverse event reports in the VAERS database supporting our hypothesis. We believe a comprehensive risk/benefit assessment of the mRNA vaccines excludes them as positive contributors to public health, even in the context of the Covid-19 pandemic.

For one century, taurine is considered as an end product of sulfur metabolism. In this review, we discuss the beneficial effect of taurine, its haloamines and taurine upregulated gene 1 (TUG1) long non-coding RNA (lncRNA) in both cancer and inflammation. We outline how taurine or its haloamines (N-Bromotaurine or N-Chlorotaurine) can induce robust and efficient responses against inflammatory diseases, providing insight into their molecular mechanisms. We also provide information about the use of taurine as a therapeutic approach to cancer. Taurine can be combined with other chemotherapeutic drugs, not only mediating durable responses in various malignancies, but also circumventing the limitations met from chemotherapeutic drugs, thus improving the therapeutic outcome. Interestingly, the lncRNA TUG1 is regarded as a promising therapeutic approach, which can overcome acquired resistance of cancer cells to selected strategies. In this regard, we can translate basic knowledge about taurine and its TUG1 lncRNA into potential therapeutic options directed against specific oncogenic signaling targets, thereby bridging the gap between bench and bedside. Contents 1. The role of taurine in inflammation 2. Formation of taurine haloamines 3. Anti-microbial properties of taurine haloamines 4. Anti-inflammatory and anti-oxidant properties of taurine haloamines 5. Therapeutic perspectives and clinical studies 6. Significance of lncRNA TUG1 lncRNA in cancer 7. The association of lncRNA TUG1 and chemoresistance 8. The role of taurine or lncRNA TUG1 as a prognostic marker 9. Conclusions