• Reproductive and Developmental Biology
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• v.42 no.2
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• pp.7-12
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• 2018

In this review, we have tried to summarize the evidence and molecular characterization indicating that $20{\alpha}$-hydroxysteroid dehydrogenase ($20{\alpha}$-HSD) is a group of the aldo-keto reductase (AKR) family, and it plays roles in the modulation and regulation of steroid hormones. This enzyme plays a critical role in the regulation of luteal function in female mammals. We have studied the molecular expression and regulation of $20{\alpha}$-HSD in cows, pigs, deer, and monkeys. The specific antibody against bovine $20{\alpha}$-HSD was generated in a rabbit immunized with the purified recombinant protein. The mRNA expression levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. The mRNA was also specifically detected in the placental and ovarian tissues during pregnancy. The $20{\alpha}$-HSD protein was intensively localized in the large luteal cells and placental cytotrophoblast villus, glandular epithelial cells of the endometrium, syncytiotrophoblast of the placenta, the isthmus cells of the oviduct, and the basal part of the primary chorionic villi and chorionic stem villus of the placenta and large luteal cells of the CL in many mammalian species. Further studies are needed to determine the functional significance of the $20{\alpha}$-HSD molecule during ovulation, pregnancy, and parturition. This article will review how fundamental information of these enzymes can be exploited for a better understanding of the reproductive organs during ovulation and pregnancy.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.368-379
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• 2022

Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

• Journal of Plant Biotechnology
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• v.50
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• pp.1-10
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• 2023

Sweet potato (Ipomoea batatas L. Lam) is an economically important root crop and a valuable source of nutrients, processed foods, animal feeds, and pigment materials. However, during post-harvest storage, storage roots of sweet potatoes are susceptible to decay caused by various microorganisms and diseases. Post-harvest curing is the most effective means of healing wounds and preventing spoilage by microorganisms during storage. In this study, we aimed to identify proteins involved in the molecular mechanisms related to curing and study proteomic changes during the post-curing storage period. For this purpose, changes in protein spots were analyzed through 2D-electrophoresis after treatment at 33℃ (curing) and 15℃ (control) for three days, followed by a storage period of eight weeks. As a result, we observed 31 differentially expressed protein spots between curing and control groups, among which 15 were identified. Among the identified proteins, the expression level of 'alpha-amylase (spot 1)' increased only after the curing treatment, whereas the expression levels of 'probable aldo-keto reductase 2-like (spot 3)' and 'hypothetical protein CHGG_01724 (spot 4)' increased in both the curing and control groups. However, the expression level of 'sporamin A (spot 10)' decreased in both the curing and control treatments. In the control treatment, the expression level of 'enolase (spot 14)' increased, but the expression levels of 'chain A of actinidin-E-64 complex+ (spot 19)', 'ascorbate peroxidase (spot 22)', and several 'sporamin proteins (spot 20, 21, 23, 24, 27, 29, 30, and 31)' decreased. These results are expected to help identify proteins related to the curing process in sweet potato storage roots, understand the mechanisms related to disease resistance during post-harvest storage, and derive candidate genes to develop new varieties with improved low-temperature storage capabilities in the future.