Glycogen synthase kinase-3 beta (GSK3β) is principally is a glycogen synthase phosphorylating enzyme that is well known for its role in muscle metabolism. GSK3β is a serine/threonine protein Kinase, which is responsible for several essential roles in mammalian cells. This enzyme is implicated in the pathophysiology of many conditions involved in homeostasis and cellular immigration. GSK3β is involved in several pathways leading to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Increasing evidence has shown the potential importance of GSK3β in ischemic heart disease and ischemia-reperfusion pathologies. Reperfusion injury may occur in tissues after prolonged ischemia following reperfusion. Reperfusion injury can be life threatening. Reperfusion injury occurs due to a change in ionic homeostasis, excess free radical production, mitochondrial damage and cell death. There are however clear, cardiac-protective signals; although the molecular pathophysiology is not clearly understood. In normal physiology, GSK3β has a critical role in the cytoprotective pathway. However, it`s controversial role in ischemia and ischemia-reperfusion is a topic of current interest. In this review, we have opted to focus on GSK3β interactions with mitochondria in ischemic heart disease and expand on the therapeutic interventions.
Today, nano-medicine promotes new therapeutics and diagnostics tools, including sensing of biomolecules as a biosensor, cancer chemotherapy and drug or gene delivery. Because of small size and biocompatibility of gold nanoparticles (GNPs), they become a good candidate for biological application. Also, thanks to their biological and chemical properties, they can mimic function of some enzymes including super oxide dismutase (SOD), esterase, etc. Also, biomaterials and bioengineering have grown so fast since the last decade for many therapeutic applications such as tissue regeneration. Among these cutting edge technology, nanomaterials find the way to becoming a very powerful tool for using in many fields of researchers including biosensing, gene therapy and chemotherapy. In this review, we focused on some biological applications of GNPs in biology and medicine.
Purpose: Cardiovascular gene therapy is a sophisticated approach, thanks to the safety of vectors, stable transgene expression, delivery method, and different layers of the heart. To date, numerous expression vectors have been introduced in biotechnology and biopharmacy industries in relation to genetic manipulation. Despite the rapid growth of these modalities, they must be intelligently designed, addressing the cardiac-specific transgene expression and less side effects. Herein, we conducted a pilot project aiming to design a cardiac-specific hypoxia-inducible expression cassette.Methods: We explored a new approach to design an expression cassette containing cardiac specific enhancer, hypoxia response elements (HRE), cardiac specific promoter, internal ribosome entry site (IRES), and beta globin poly A sequence to elicit specific and inducible expression of the gene of interest. Enhanced green fluorescent protein (eGFP) was sub-cloned by BglII and NotI into the cassette. The specificity and inducible expression of the cassette was determined in both mouse myoblast C2C12 and mammary glandular tumor 4T1 as ‘twin’ cells. eGFP expression was evaluated by immunofluorescence microscope and flow cytometry at 520 nm emission peak.Results: Our data revealed that the designed expression cassette provided tissue specific and hypoxia inducible (O2<1%) transgene expression.Conclusion: It is suggested that cardiac-specific enhancer combined with cardiac-specific promoter are efficient for myoblast specific gene expression. As well, this is for the first time that HRE are derived from three well known hypoxia-regulated promoters. Therefore, there is no longer need to overlap PCR process for one repeated sequence just in one promoter.
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