• Journal of Life Science
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• v.31 no.2
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• pp.248-255
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• 2021

Mammary gland tumors are one of the most common cancers in female dogs, and there are various types of cells depending on the tumor type. Complex carcinoma consists of a combination of luminal epithelial and myoepithelial cells with intra-tumoral heterogeneity. However, the origins of these tumor cells and their effects on the malignancies of tumors have not been identified. Recently, it has been reported that cancer stem cells, identified in several types of human tumors, are involved in tumor heterogeneity and may also contribute to malignancies such as tumor recurrence and metastasis. Interestingly, cancer stem cells share several abilities of self-renewal and cell differentiation into multiple types of cancer cells, but they have abnormal genetic mutation and signal transduction pathways to regulate the maintenance of stem cell characters. Moreover, it is known that these cell populations contribute to cell metastasis as well as cell resistance against chemo- and radio-therapeutics that promote tumor recurrence. The existence of cancer stem cells might explain the intra-tumoral heterogeneity and cancer aggressiveness during tumorigenesis in canine mammary gland tumors. This review summarizes the characteristics and types of canine mammary gland tumors, the definition of tumor stem cells, methods of isolation, and clinical significance.

• Journal of Practical Agriculture & Fisheries Research
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• v.23 no.1
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• pp.117-128
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• 2021

The skeletal muscle development of Hanwoo steer has been processed in the prenatal and postnatal periods. Bovine satellite cell located in perimysium of muscle tissues has differentially distributed in peripheral tissues. The study of postnatal development of satellite cells can help understand the genetic and functional regulation of meat characteristics. Factors affecting muscle size increase are related to the accumulation of DNA or synthesis of RNA proteins. In this study, we observed muscle development and differentiation after culturing bovine satellite cells derived from longissimus dorsi and semimembranosus regions of Hanwoo muscle tissue. In addition, RNA sequencing data were analyzed for differentially expressed genes (DEG) involved in intracellular muscle development and growth. The DEG of the two muscle tissues were compared according to 1day, 2day, 4day, and 7day. The overall gene expression level was confirmed by the heat map. Gene Ontology (GO) classification method was used to compare the expression level of gene groups affecting LD and SM development. The histology of GO was consistent with the time-cause change of LD and SM cell morphology. SM showed more active skeletal muscle development than LD. Even within the same time, SM expressed more genes than LD, thus synthesizing more muscle fibers

• Korean Journal of Ichthyology
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• v.32 no.4
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• pp.199-209
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• 2020

In order to clarify the taxonomic status of the Korean Macroramphosus species, which were previously confused, we investigated morphological and molecular variations of Macroramphosus (18 individuals) from Korea, and Macroramphosus (35 individuals) from Japan and Taiwan, and compared with those of M. scolopax from type locality (Mediterranean Sea). Although the Korean and Japanese specimens of Macroramphosus were clearly divided into two types in the first dorsal spine length (22.8~32.1% in A-type vs. 15.6~21.4% in B-type), distance between the first dorsal fin and second dorsal fin (6.4~9.7% vs. 8.6~13.3%), and body depth (20.0~28.0% vs. 17.3~22.6%), no genetic differences among all individuals of longspine snipefish between them were found at the specific level [d=0.0~3.3% in control region (CR); 0.0~1.3% in cytochrome b (cytb); 0.0~0.5% in cytochrome c oxidase subunit I (COI)]. Whereas, they were well distinguished in genetics (9.9~11.5% in CR; 3.8~4.6% in cytb; 1.2~3.6% in COI) from those of M. scolopax in Mediterranean Sea. It needs the scientific name of the longspine snipefish (M. scolopax) in Korea be changed as M. japonicus (and/or M. sagifue). However, our results could not find evidence of consistency between morphological and mitochondrial DNA variations which suggests that their differentiation event may occur fairly recently. Further studies using more sensitive markers such as microsatellite are needed to clarify the degree of gene flow between the two types.

• Journal of Life Science
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• v.31 no.12
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• pp.1120-1127
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• 2021

Depression has a negative impact on social functioning due to its high prevalence and increased suicide rate, and is a disease with a high economic burden. Depression is related to diverse brain-related phenomena, such as neuroinflammation, synaptic dysfunction, and cognitive deficit. As antidepressant drugs used in clinical trials have shown poor therapeutic effects, antidepressant drugs that show rapid efficacy urgently need to be developed. Although studies on various genes, proteins, and signaling pathways related to depression have been conducted, the pathogenesis of depression has not been clearly elucidated. Sirtuin 1 is a nicotinamide-adenine dinucleotide- (NAD+-) dependent histone deacetylase and is involved in cell differentiation, apoptosis, autophagy, and cancer metabolism. Recent genetic studies found that sirtuin 1 is a potential target gene for depression. In addition, preclinical studies reported that sirtuin 1 signaling affects depression-like behavior. In this review, we attempt to present up-to-date knowledge of depression and sirtuin 1. We describe the various roles of sirtuin 1 in the regulation of glial activation, circadian rhythm, neurogenesis, and cognitive function and the effects of its expression on depression. Further, we discuss the effect of sirtuin 1 on the impairment of neural plasticity, one of the key mechanisms of depression, and the associated mechanisms of sirtuin 1.

• Journal of Mushroom
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• v.20 no.4
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• pp.218-226
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• 2022

Flammulina velutipes, known as winter mushroom in the family of Physalacriaceae, is the main edible and export mushroom with the third highest production after oyster and king oyster mushroom in Korea. However, as normal consumers regard F. velutipes as a simple subsidiary material, there is a limitation to increasing mushroom demand. In order to overcome the consumption limit and increase the differentiation of new varieties, it is necessary to breed varieties with enhanced functionality in consideration of consumer preferences. Therefore, the study was performed to analyze nutrient components and several useful functional substances with 26 genetic resources of F. velutipes. Analyses of inorganic compound(Ca, K, Mg) and 15 amino acids revealed that Strain 4148 had the highest content among the 26 strains. Beta-glucan, which increases immune activity and polyphenol, which exert antioxidant effects were higher in non-white strains than in white strains with a small number of exceptions. Among the five fatty acids, linoleic acid(an omega-6 fatty acid) and α-linolenic acid(an omega-3 fatty acid), were detected in six mushroom strains. α-linolenic acid, which was not found in five major mushrooms including oyster mushrooms, was identified in F. velutipes. The results of HPLC analysis showed that 'Auram' (Strain 4232) and 'Baekseung'(Strain 4230) had the highest content of the stabilizing neurotransmitter GABA(15.38 ㎍/ml and 20.56 ㎍/ml, respectively) among non-white and white strains, respectively. Our findings provide useful information for breeding F. velutipes to obtain strains with enhanced functionality.

• Journal of Life Science
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• v.32 no.6
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• pp.476-481
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• 2022

Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1206-1212
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• 2023

The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N⁶-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

• Korean Journal of Plant Resources
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• v.36 no.5
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• pp.527-539
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• 2023

Pepper (Capsicum annuum L.) is an important vegetable and spice crop that has been cultivated worldwide. Pepper fruits have unique taste and aroma, providing a variety of antioxidants and compounds important for human health, which makes a high economic value. In addition, there is a high demand for new pepper varieties, according to consumer's preference. However, pepper is a recalcitrant plant for in vitro tissue and organ differentiation and plant regeneration, which makes it difficult to develop demanded varieties using newly developed technologies such as genetic engineering and gene editing. In this study, tissue culture and regeneration conditions were investigated using seven pepper varieties that were obtained from the core-collection of Seoul National University. We observed callus and bud induction and shoot formation using several media composition composed of different cytokinins and auxin concentrations. As a result, it was found that there were differences in callus induction and shoot formation of each variety depending on the hormone composition, and the highest regeneration was shown when the medium containing Zeatin Riboside and the petioles of seedlings were used. In particular, out of seven pepper varieties, CMV980 exhibited a higher regeneration efficiency (approximately 48%) than other varieties, followed by Yuwolcho. Therefore, this study provides CMV980 and Yuwolcho as good candidates that can be used for pepper transformation, which might contribute to the development of various varieties through gene editing technology in the future.

• Korean Journal of Clinical Laboratory Science
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• v.56 no.3
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• pp.207-216
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• 2024

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by both genetic and environmental factors. Fludarabine is a selective inhibitor of signal transducer and activator of transcription 1 (STAT1). Recently, STAT1 inhibitors have been considered potential treatments for SLE, due to the relationship between its pathogenesis and STAT1 pathway-mediated cytokines such as interferons. In the current study, we evaluated the therapeutic effects of fludarabine in an SLE animal model and explored its effects on T cell responses. 12-week-old C57BL/6 mice with topically administered R848 exhibited lupus-like phenotypes. Disease activity, such as proteinuria, autoantibody levels, immunoglobulin titers, the histological score, and C3 deposition, greatly improved with fludarabine treatment. In addition, fludarabine inhibited CD4⁺ T cells and T helper 1 (Th1) cells in the spleen and significantly decreased the differentiation of Th1 cells in vitro. These results indicate that Th1 cells play a critical role in the pathogenesis of lupus nephritis (LN). Thus, fludarabine exerted therapeutic effects on lupus animal models by suppressing Th1 cells via STAT1 inhibition. We propose that targeting STAT1 signaling using fludarabine could be an effective therapy for treating LN.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.