• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.1
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• pp.1-14
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• 2019

Objectives: This study was designed to investigate the effect of Bombycis corpus on reproductive dysfunction caused by aging. Methods: The experimental group was divided into three groups: a control group consisting of 8-week-old male ICR mice without any treatment, An aging-elicited group (AE group) consisting of 50-week-old ICR male mice without any treatment, and a Bombycis corpus treatment group (BC group) consisting of 50-week-old ICR male mice with treatment Bombycis corpus extract (0.78 g/kg/day) for 6 months. After 6 months, histochemistry and immunohistochemistry of the testis were performed to investigate the effects of Bombycis corpus on the reproductive dysfunction caused by aging. Results: In the first step, Bombycis corpus increased spermatogenesis and distribution of sertoli cells in the seminiferous tubule, increased BrdU positive reaction in the spermatogonium at the basal part of the seminiferous tubule, and decreased the apoptosis of Sertoli cells in the seminiferous tubule. In addition, Bombycis corpus increased AR positive in Sertoli cells and $17{\beta}-HSD$ positive in leydig cells. Finally, Bombycis corpus decreased 8-OHdG positivite reaction in the spermatids of the seminiferous lumen, caspase-3 positivity in leydig cells, and HDAC1 positivite reaction in sertoli cells. Conclusions: These results suggest that Bombycis corpus increases spermatogenesis, decreases apoptosis of leydig cells and Sertoli cells, increases the production and action of testosterone in the testis, and inhibits DNA damages and DNA transcripts decrease in the testis, Thereby improving reproductive dysfunction caused by aging.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.184-194
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• 2021

Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

• Journal of Medicine and Life Science
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• v.18 no.3
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• pp.41-48
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• 2021

The prevalence of attention deficit hyperactivity disorder (ADHD), a developmental neuropsychiatric disorder, is high among children and adolescents. The pathogenesis of ADHD is mediated with genetic, biological, and environmental factors. Most therapeutic drugs for ADHD have so far targeted biological causes, primarily by regulating catecholaminergic neurotransmitters. However, ADHD drugs that are clinically treated have various problems in their addictiveness and drug stability; thus, it is recommended that efficacy and safety should be secured through simultaneous prescription of multiple drugs rather than a single drug treatment. Accordingly, it is necessary to develop drugs that newly target pathogenic mechanisms of ADHD. In this study, we attempt to confirm the possibility of developing new drugs by reviewing dopamine-related developmental mechanisms of neurons and their correlation with ADHD. Histone deacetylase inhibitors (HDACi) can regulate the concentration of intracellular dopamine in neurons by expressing vesicular monoamine transporter 2 and inducing the exocytosis of neurotransmitters to the synaptic cleft, thereby promoting the development of neurons and signal transmission. This cellular modulation of HDACi is expected to treat ADHD by regulating endogenous catecholamines such as dopamine. Although studies are still in the preclinical stage, HDAC inhibitors clearly have potential as a therapeutic agent with low addictiveness and high efficacy for ADHD treatment.

• Food Science of Animal Resources
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• v.43 no.4
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• pp.703-711
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• 2023

As an initial study to elucidate the molecular mechanism of how probiotics modulate macrophage activity, we monitored mRNA expression patterns in peritoneal macrophages (PMs) treated with two different strains of probiotics. After treatment with either Weissella cibaria WIKIM28 or Latilactobacillus sakei WIKIM50, total RNAs from PMs were isolated and subjected into gene chip analyses. As controls, mRNAs from vehicle (phosphate-buffered saline, PBS)-treated PMs were also subjected to gene chip analysis. Compared to vehicle (PBS)-treated PMs, WIKIM28-treated and WIKIM50-treated PMs exhibited a total of 889 and 432 differentially expressed genes with expression differences of at least 4 folds, respectively. Compared to WIKIM28-treated PMs, WIKIM50-treated PMs showed 25 up-regulated genes and 21 down-regulated genes with expression differences of more than 2 folds. Interestingly, mRNA transcripts of M2 macrophage polarization marker such as anxa1, mafb, and sepp1 were increased in WIKIM50-treated PMs comparing to those in WIKIM28-treated PMs. Reversely, mRNA transcripts of M1 macrophage polarization marker such as hdac9, ptgs2, and socs3 were decreased in WIKIM50-treated PMs comparing to those in WIKIM28-treated PMs. In agreement with these observations, mRNA expression levels of tumor necrosis factor-α and interleukin-1α were significantly reduced in WIKIM50-treated macrophages compared to those in WIKIM28-treated macrophages. These results may indicate that probiotics can be classified as two different types depending on their ability to convert macrophages into M1 or M2 polarization.

• Genomics & Informatics
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• v.21 no.3
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• pp.31.1-31.8
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• 2023

Multiple myeloma (MM) is a hematological malignancy. It is widely believed that genetic factors play a significant role in the development of MM, as investigated in numerous studies. However, the application of genomic information for clinical purposes, including diagnostic and prognostic biomarkers, remains largely confined to research. In this study, we utilized genetic information from the Genomic-Driven Clinical Implementation for Multiple Myeloma database, which is dedicated to clinical trial studies on MM. This genetic information was sourced from the genome-wide association studies catalog database. We prioritized genes with the potential to cause MM based on established annotations, as well as biological risk genes for MM, as potential drug target candidates. The DrugBank database was employed to identify drug candidates targeting these genes. Our research led to the discovery of 14 MM biological risk genes and the identification of 10 drugs that target three of these genes. Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1437-1447
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• 2023

A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.138-141
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• 2004

Purpose : We have previously reported that human glioblastoma cells are sensitized to radiation-induced death after their exposure to trichostatin A (TSA), a histone deacetylase inhibitor (HDAC-1), prior to the irradiation. We aimed to measure the magnitude of the radiosensitizing effect of TSA in human head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines, HN-3 and HN-9, were exposed to 0, 50, 100, and 200 nM TSA for 18 hr prior to irradiation. Then, the TSA-treated cells were irradiated with 0, 2, 4, 6, and 8 Gy, and cell survival was measured by clonogenic assay. Results : Pre-irradiation exposure to TSA was found to radiosensitize HN-3 and HN-9 cell lines. In HN-9 cells, the fraction surviving after 2 Gy (SF2) was significantly reduced by treatment of TSA at concentration as low as 50 nM. However, a treatment with 200 nM TSA was required to significantly decrease SF2 in the HN-3 cell line. SER of pre-irradiation treatment with 200 nM TSA was 1.84 in HN-3 and 7.24 in HN-9, respectively. Conclusions : Our results clearly showed that human head and neck cancer cell lines can be sensitized to ionizing radiation by pre-irradiation inhibition of histone deacetylase (HDAC) using TSA, and that this potentiation might well be a general phenomenon.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.116-122
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• 2005

Purpose: Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components of anticancer therapy and their radiosensitizing effects have become evident. Specific HDAS are now available that preferentially inhibit specific HDAC classes; TSA inhibits Class I and II HDACs, and SK7041 inhibits Class I HDACs. Materials and methods: We tested the differential radiosensitization induced by two different classes of HDIs in HeLa cells. We next tested the hypothesis that p53 expression in cancer cells may influence the susceptibility to HDIs by using pharmacologic modification of the p53 status under an isogenic background. Results: It is interesting that p53 expression in the HeLa cells clearly increased the degree of radio-sensitization by TSA compared to that of the class I specific inhibitor SK7041. This suggests that p53 may, in part, be responsible for the mechanistic role for the greater radiosensitization induced by Class I & II inhibitors compared to that of the class I specific inhibitors. Thus, these studies are useful in distinguishing between events mediated solely by the Class I HDACS versus those events involving the other classes of HDACS as well. Conclusion: The anticancer efficacy of targeting Class I and II HDACS, in conjunction with radiation therapy, may be further enhanced by the restoration of p53 expression.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.3
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• pp.302-309
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• 2008

Epigenetic is usually referring to heritable traits that do not involve changes to the underlying DNA sequence. DNA methylation is known to serve as cellular memory. and is one of the most important mechanism of epigenetic. DNA methylation is a covalent modification in which the target molecules for methylation in mammalian DNA are cytosine bases in CpG dinucleotides. The 5' position of cytosine is methylated in a reaction catalyzed by DNA methyltransferases; DNMTl, DNMT3a, and DNMT3b. There are two different regions in the context of DNA methylation: CpG poor regions and CpG islands. The intergenic and the intronic region is considered to be CpG poor, and CpG islands are discrete CpG-rich regions which are often found in promoter regions. Normally, CpG poor regions are usually methylated whereas CpG islands are generally hypomethylated. DNA methylation is involved in various biological processes such as tissue-specific gene expression, genomic imprinting, and X chromosome inactivation. In general. cancer cells are characterized by global genomic hypomethylation and focal hypermethylation of CpG islands, which are generally unmethylated in normal cells. Gene silencing by CpG hypermethylation at the promotors of tumor suppressor genes is probably the most common mechanism of tumor suppressor inactivation in cancer.

• Journal of Life Science
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• v.30 no.1
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• pp.96-105
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• 2020

Sirtuin inhibitors are pharmaceutically and therapeutically valuable compounds that inhibit sirtuin, a type III histone deacetylase. Synthetic sirtuin inhibitors were discovered and characterized using cell-based screens in yeast (Saccharomyces cerevisiae) and have been used in the study of aging, carcinogenesis, and diabetes, all of which are related to sirtuin function. For medical applications, synthetic inhibitors have been further developed for increased potency and specificity, including compounds containing nicotinamide, thioacetyl lysine, β-naphthol, and indole derivatives. Suramin, tenovin, and their analogues were developed as a result. Sirtuin inhibitors were found to affect organic development and have been used to genetically modify plants, although a sirtinol-resistant mutation in the biosynthesis of a molybdopterin cofactor for an aldehyde oxidase has been identified. Some natural flavonoids, and catechin and quercetin derivatives also act as sirtuin inhibitors have been studied to identify a more potent inhibitor for therapeutic purposes. In this review, sirtuin is introduced and the therapeutic inhibitors that have been developed are presented, particularly sirtinol which has been used for genetic modification in plants though it was not designed to be so. Sirtuin inhibitors with greater potency and selectivity are required and those developed in pharmaceutics should be used in plant research to identify more authentic sirtuins in plants.