In-Sun Yu

Phenylketonuria (PKU) is an inherited disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene that result in the amino acid phenylalanine (Phe) building up in the blood. Current therapies suggest low-Phe dietary management and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH₄) therapy, which are limited in efficacy and require lifelong treatment. Recent advances in gene therapy, including gene editing and viral-mediated gene delivery, produce therapeutic effects. Advancements in gene editing technologies, notably adenine base editors (ABEs) and CRISPR-based systems, in conjunction with enhanced delivery methods such as lipid nanoparticles (LNPs) and recombinant viruses, have demonstrated substantial promise in preclinical studies. This review details the pathophysiology of PKU treatment, and progress in preclinical and clinical gene therapy strategies. Emphasis is on adenine base editing using LNPs, recombinant adeno-associated virus (rAAV)-mediated gene transfer, and the translational challenges associated with these technologies. We also discuss future directions for therapeutic reach and ensuring long-term safety and efficacy.

Olfactory receptors (ORs), which are primarily responsible for olfactory sensation in the nasal epithelium, constitute the largest family of genes in the human genome. The majority of ORs are orphan receptors with unknown ligands; however, recent studies have revealed their expression in non-olfactory tissues, implying that ORs may be involved in various physiological processes beyond olfaction. This review highlights recent findings on the roles of ORs in cancers, including prostate, breast, and lung cancer, as well as their involvement in other diseases, such as atherosclerosis, Alzheimer's disease, and viral infections. Additionally, we explore emerging knowledge about the role of ORs in metabolic regulation, focusing on their effect on triglyceride metabolism, glucagon-like peptide-1 secretion, and lipid accumulation. Advancements in technology, such as structural analysis, have accelerated research on OR ligands and their functions, potentially positioning ORs as novel therapeutic targets for various diseases. This review highlights the need for further research into the non-olfactory roles of ORs and their potential as targets for future therapeutic interventions.

The principles of myogenesis play crucial roles in the production of cultured meat, and identifying protein stimulators associated with myogenesis holds great potential to enhance the efficiency of this process. In this study, we used surface plasmon resonance (SPR)-based screening of a natural product library to discover ligands for Pax7 and MyoD, key regulators of satellite cells (SCs), and performed cell-based assays on Hanwoo SCs (HWSCs) to identify substances that promote cell proliferation and/or differentiation. Through an SPR analysis, we found that six chemicals, including one Pax7+/MyoD− chemical, four Pax7+/MyoD+ chemicals, and one Pax7−/MyoD+ chemical, bound to Pax7 and/or MyoD proteins. Among four Pax7+/MyoD+ chemicals, parthenolide (0.5 and 1 µM) and rutin (100 and 200 µM) stimulated cell proliferation in the medium with 10% FBS similar to the medium with 20% FBS, without affecting differentiation. Adenosine, a Pax7−/MyoD+ chemical, accelerated differentiation. These chemicals could be potential additives to reduce the reliance of FBS required for HWSC proliferation and differentiation in cultured meat production.

Food Science of Animal Resources (Food Sci. Anim. Resour.) is an international, peer-reviewed bimonthly journal publishing original research and reviews on basic and applied aspects of the use of animal resources including the meat, egg, dairy, and edible insect/worm products. Food Sci. Anim. Resour. is published and distributed by the Korean Society for Food Science of Animal Resources.

In-sun Yu, Sang Yoon Choi, Jungseok Choi, Mina K. Kim, and Min Jung Kim. Journal of the Korean Society of Food Science and Nutrition 2022;51:1036-47. https://doi.org/10.3746/jkfn.2022.51.10.1036

In age-related macular degeneration, N-retinylidene-N-retinylethanolamine (A2E) accumulates in retinal pigment epithelium (RPE) cells and generates oxidative stress, which further induces cell death. Polyphenols are well known for their antioxidant and beneficial effects on vision. Chrysanthemum boreale Makino (CB) flowers, which contain flavonoids, have antioxidant activity. We hypothesized that polyphenols in ethanolic extracts of CB (CBE) and its fractions suppressed A2E-mediated ARPE-19 cell damage, a human RPE cell line. CBE is rich in polyphenols, shows antioxidant activity, and suppresses intracellular accumulation of A2E and cell death induced by A2E. Among the five fractions, the polyphenol content and antioxidant effect were in the order of the ethyl acetate fraction (EtOAc) > butanol fraction (BuOH) > hexane fraction (Hex) > dichloromethane fraction (CH₂Cl₂) > water fraction (H₂O). In contrast, the inhibitory ability of A2E accumulation and A2E-induced cell death was highest in H₂O, followed by BuOH. In the correlation analysis, polyphenols in the H₂O and BuOH fractions had a significant positive correlation with antioxidant effects, but no significant correlation with cell damage caused by A2E. Our findings suggest that substances other than polyphenols present in CBE can suppress the effects of A2E, and further research is needed.