• Journal of Veterinary Science
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• v.25 no.2
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• pp.23.1-23.15
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• 2024

The widespread use of antimicrobials causes antibiotic resistance in bacteria. The use of butyric acid and its derivatives is an alternative tactic. This review summarizes the literature on the role of butyric acid in the body and provides further prospects for the clinical use of its derivatives and delivery methods to the animal body. Thus far, there is evidence confirming the vital role of butyric acid in the body and the effectiveness of its derivatives when used as animal medicines and growth stimulants. Butyric acid salts stimulate immunomodulatory activity by reducing microbial colonization of the intestine and suppressing inflammation. Extraintestinal effects occur against the background of hemoglobinopathy, hypercholesterolemia, insulin resistance, and cerebral ischemia. Butyric acid derivatives inhibit histone deacetylase. Aberrant histone deacetylase activity is associated with the development of certain types of cancer in humans. Feed additives containing butyric acid salts or tributyrin are used widely in animal husbandry. They improve the functional status of the intestine and accelerate animal growth and development. On the other hand, high concentrations of butyric acid stimulate the apoptosis of epithelial cells and disrupt the intestinal barrier function. This review highlights the biological activity and the mechanism of action of butyric acid, its salts, and esters, revealing their role in the treatment of various animal and human diseases. This paper also discussed the possibility of using butyric acid and its derivatives as surface modifiers of enterosorbents to obtain new drugs with bifunctional action.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.435-446
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• 2022

The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

• Biomedical Science Letters
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• v.30 no.2
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• pp.37-48
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• 2024

Liposomes are one of the most actively studied and promising drug delivery systems for the treatment of various diseases. In this study, an aptamer-conjugated liposome called "aptamosome" was used, in which an anti-PD-L1 aptamer targeting cancer cells was conjugated to the liposome. These aptamosomes showed remarkable cellular uptake and efficient delivery to Lewis lung carcinoma 2 (LL/2) cancer cells. In addition, suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), was delivered through this aptamer to induce a strong anticancer immunotherapeutic effect. The results of this study showed that when LL/2 cells were treated with SAHA-entrapped aptamosome [SAHA] and liposome [SAHA] and free SAHA, aptamosome [SAHA] improved cell death compared with that of liposomes [SAHA] or free SAHA, and it has demonstrated anticancer efficacy. Moreover, aptamosome [SAHA] induce the secretion of chemokines that promote the migration of activated T cells into tumor tissues. Finally, in vivo experiments showed that aptamosome [SAHA] significantly inhibited the growth rate of LL/2 tumors. Therefore, liposomes combined with an anti-PD-L1 aptamer for efficient SAHA delivery are suggested as an excellent model for drug delivery systems suitable for targeting cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4663-4670
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• 2014

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferation and apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylation alteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate of cell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Compared to control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to induce genome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylation level of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that many genes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation. Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally, we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNA methylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although many unreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers to new biomarkers and therapeutic strategies in the treatment of NPC should be stressed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3397-3401
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• 2014

Determining cell quantity is a common problem in cytology research and anti-tumor drug development. A simple and low-cost method was developed to determine monolayer and adherent-growth cell quantities. The cell nucleus is located in the cytoplasm, and is independent. Thus, the nucleus cannot make contact even if the cell density is heavy. This phenomenon is the foundation of accurate cell-nucleus recognition. The cell nucleus is easily recognizable in images after fluorescent staining because it is independent. A one-to-one relationship exists between the nucleus and the cell; therefore, this method can be used to determine the quantity of proliferating cells. Results indicated that the activity of the histone deacetylase inhibitor Z1 was effective after this method was used. The nude-mouse xenograft model also revealed the potent anti-tumor activity of Z1. This research presents a new anti-tumor-drug evaluation method.

• Horticultural Science & Technology
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• v.35 no.3
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• pp.323-332
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• 2017

Homology-specific transcriptional and post-transcriptional silencing, an intrinsic mechanism of gene regulation in most eukaryotes, can be induced by anti-sense, co-suppression, or hairpin-based double-stranded RNA. Hairpin-based RNA interference (RNAi) has been applied to analyze gene function and genetically modify crops. However, RNAi vector construction usually requires high-cost cloning steps and large amounts of time, or involves methods that are protected by intellectual property rights. We describe a more effective method for generating intron-spliced RNAi constructs. To produce intron-spliced hairpin RNA, an RNAi cassette was ligated with the first intron and splicing sequences of the Brassica rapa ssp. pekinensis histone deacetylase 1 gene. This method requires a single ligation of the PCR-amplified target gene to SpeI-NcoI and SacI-BglII enzyme sites to create a gene-specific silencing construct. We named the resulting binary vector system pKHi and verified its functionality by constructing a vector to silence DIHYDROFLAVONOL 4-REDUCTASE (DFR), transforming it into tobacco plants, and confirming DFR gene-silencing via PCR, RT-qPCR, and analysis of the accumulation of small interfering RNAs. Reduction of anthocyanin biosynthesis was also confirmed by analyzing flower color of the transgenic tobacco plants. This study demonstrates that small interfering RNAs generated through the pKHi vector system can efficiently silence target genes and could be used in developing genetically modified crops.

• KSBB Journal
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• v.26 no.2
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• pp.107-111
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• 2011

The essential operating parameters in virus vaccine production are multiplicity of infection (MOI), harvest time, and infection time. Stimulating agents also can be applied in order to improve vaccine productivity further. We investigated the optimum operating conditions in porcine transmissible gastroenteritis virus (TGEV) vaccine production and the applicability of sodium butyrate (NaBu) as a stimulating agents for the improvement of vaccine productivity. The optimum MOI, infection time, and harvest time for high production of TGEV by swine testicle (ST) cells were found to be 0.0001 pfu/cell, 3 day after cell inoculation, and 24 hpi, respectively. NaBu is known as a histone deacetylase inhibitor that has been widely used for the high expression of recombinant protein using mammalian cells and for the enhancement of virus propagation. So we tried to examine the potential of NaBu as a stimulating agent and to determine the optimum concentration by comparing TGEV titers with different range of NaBu concentration. TGEV titer with 5 mM NaBu was 1.5 times higher than control. Therefore, we concluded that NaBu can be a promising agent for stimulating various vaccine production including TGEV and the optimum NaBu concentration for TGEV production was determined to be 5 mM.

• Journal of Life Science
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• v.27 no.4
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• pp.482-499
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• 2017

Allergic diseases have increased over the past several decade worldwide including developing countries. Allergic inflammatory responses are caused by Th (T helper)2 immune responses, triggered by allergen ingestion by antigen presenting cells such as dendritic cells (DCs). Intestinal microorganisms control the metabolism and physiological functions of the host, contribute to early immune system maturation during the early life, and homeostasis and epithelial integrity during life. Bifidobacteria have strain-specific immunostimulatory properties in the Th1/Th2 balance, inhibit TSLP (thymic stromal lymphopoietin) and IgE expression, and promote Flg (Filaggrin) and FoxP3 (Treg) expression to alleviate allergies. In addition, unmethylated CpG motif ODN (oligodeoxynucleotides) is recognized by TLR (toll-like receptors)9 of B cells and plasmacytoid dendritic cells (pDCs) to induce innate and adaptive immune responses, while the butyrate produced by Clostridium butyricum activates the GPR (G-protein coupled receptors)109a signaling pathway to induce the expression of anti-inflammatory gene of pDCs, and directly stimulates the proliferation of thymically derived regulatory T (tTreg) cells through the activation of GPR43 or inhibits the activity of HADC (histone deacetylase) to differentiate naive $CD4^+$ T cells into pTreg cells through the histone H3 acetylation of Foxp3 gene intronic enhancer.

• Journal of Life Science
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• v.13 no.1
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• pp.128-135
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• 2003

102 ESTs (Expressed Sequence Tags) were obtained by sequencing clones from a library of rainbow trout kidney cDNAs. Of the sequences generated, 55.8% of the ESTs were represented by 37 known genes. The 45 clones of unknown gene products potentially represent 40 novel genes. The genes involved in structural function (14.5%) and transcription/translation (11.6%) account for the major gene expression activities in the kidney Microarray experiment was conducted to compare gene expression of the unique ESTs in young and adult rainbow trout kidneys. While mitochondrion, cytochrome b, rho G, spastin protein, and three unknown genes were down-regulated in the mature fish kidney, calponin 1, calcium binding protein, histone deacetylase 1, and an unknown gene were up-regulated in the mature fish kidney. This research demonstrates the feasibility and power of functional genomics in rainbow trout.

• Oncology Letters
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• v.41 no.6
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• pp.3464-3474
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• 2019

The EF-hand calcium binding protein tescalcin (TESC) is highly expressed in various human and mouse cancer tissues and is therefore considered a potential oncogene. However, the underlying mechanism that governs TESC expression remains unclear. Emerging evidence suggests that TESC expression is under epigenetic regulation. In the present study, the relationship between the epigenetic modification and gene expression of TESC in gastric cancer was investigated. To evaluate the relationship between the methylation and expression of TESC in gastric cancer, the methylation status of CpG sites in the TESC promoter was analyzed using microarray with the Illumina Human Methylation27 BeadChip (HumanMethylation27_270596_v.1.2), gene profiles from the NCBI Dataset that revealed demethylated status were acquired, and real-time methylation-specific PCR (MSP) in gastric cancer cells was conducted. In the present study, it was demonstrated that the hypermethylation of TESC led to the downregulation of TESC mRNA/protein expression. In addition, 5-aza-2c-deoxycytidine (5'-aza-dC) restored TESC expression in the tested gastric cancer cells except for SNU-620 cells. ChIP assay further revealed that the methylation of the TESC promoter was associated with methyl-CpG binding domain protein (MBD)1, histone deacetylase (HDAC)2, and Oct-1 and that treatment with 5'-aza-dC facilitated the dissociation of MBD1, HDAC2, and Oct-1 from the promoter of TESC. Moreover, silencing of TESC increased MBD1 expression and decreased the H3K4me2/3 level, thereby causing transcriptional repression and suppression of cell survival in NCI-N87 cells; conversely, overexpression of TESC downregulated MBD1 expression and upregulated the H3K4me2 level associated with active transcription in SNU-638 cells. These results indicated that the differential expression of TESC via the modification status of the promoter and histone methylation controled cell survival in gastric cancer cells. Overall, the present study provided a novel therapeutic strategy for gastric cancer.