临床与医学基因组学杂志

Iron is a micronutrient essential for fundamental cellular processes. Iron deficiency has been proven to be the leading course of some blood diseases. Though essential, iron overload may contribute to the generation of free radicals capable for cell damaging. As such, the maintenance and control of iron homeostasis is critical to prevent either iron deficiency or iron overload toxicity. Iron homeostasis is largely coordinated by a family of Iron Regulatory Proteins (IRP) that functions to control iron uptake, storage, transport, and utilization. More recently, iron metabolism has also been implicated in the modulation of microRNA (miRNA), a class of small non-coding RNA recognized as the major regulation mechanism for gene expression at post-transcriptional level. Vice versa, miRNAs have been demonstrated to regulate the expression of genes associated with iron acquisition (transferrin receptor and divalent metal transporter), iron export (ferroportin), iron storage (ferritin), iron utilization (ISCU), and coordination of systemic iron homeostasis (HFE and hemojevelin), bridging the crosstalk between miRNAs regulation and iron homeostasis. Herein we briefly summarize recent advances in the inter-regulation between miRNAs and maintenance of iron homeostasis. It will enhance our understanding of mechanisms by which cells respond to changes in iron demand and/or iron availability to control cellular iron homeostasis, and how miRNAs regulate iron homeostasis.

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) can cause skeletal muscle toxicity; the risk of toxicity is elevated by drug interactions and pharmacogenetic factors that increase the concentration of statins in plasma.

The genetic basis of statin-related muscle disorders is largely unknown. Statins are substrates for several membrane transporters that may mediate drug interactions. Potent inhibitors of cytochrome P450 (CYP450) especially CYP3A4, can significantly increase the plasma concentrations of the active forms of atorvastatin, lovastatin and simvastatin. Fluvastatin, which is metabolized by CYP2C9, is less prone to pharmacokinetic interactions, while pravastatin and rosuvastatin are not susceptible to any CYP inhibition. OATP1B1 can decrease the hepatic uptake of many statins, as well as the therapeutic index of these agents. Polymorphisms of CYP450 enzymes, SLCO1B1, ABCB1, and COQ2 gene, can induce statin intolerance. This review summarized the principal relations known between statin myotoxicity and genetic risk factors.

Nucleic acids-based technology is emerging as a valuable field that integrates research from science and technology to create novel nanodevices and nanostructures with various applicationsin modern nanotechnology. Nowadays, applicationsof RNA-based technologyare employed in biomedical and pharmaceutical research, biosensoring, nanopharmaceutics and others. It has been proven that RNA isa very suitable medium for selfassembly of diverse nanostructures, catalytic nanodevices and cell delivery systems.At the same time, genomics is becoming increasingly valuable for modern medicine due to the advancements made by second generation sequencing technologies. In this review, I discuss various applications of designer ribozymes and diverse RNAbased approaches to medical genomics. The areas discussed include RNA-based approaches for molecular sensoring and diagnostics, antibacterial drug discovery, exogenous control of gene expression, and gene silencing. These approaches havebecomepossible due to the advancement of various methods for engineering functional RNAsas well asthe discoveries made in RNA biology. Furthermore, different RNA-based antisense technologies are reviewed together with methods for nucleic acid delivery to the cell. The research that has been done so far in the field of RNA engineering hasa far-reaching impact on medical genomics, which isthe main focus of this review.