• Animal Bioscience
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• v.36 no.1
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• pp.29-42
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• 2023

Objective: Pigs, an ideal biomedical model for human diseases, suffer from about 50% early embryonic and fetal death, a major cause of fertility loss worldwide. However, identifying the causal variant remains a huge challenge. This study aimed to detect single nucleotide polymorphisms (SNPs) and candidate genes for the number of mummified (NM) piglets using the imputed whole-genome sequence (WGS) and validate the potential candidate genes. Methods: The imputed WGS was introduced from genotyping-by-sequencing (GBS) using a multi-breed reference population. We performed genome-wide association studies (GWAS) for NM piglets at birth from a Landrace pig populatiGWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase on. A total of 300 Landrace pigs were genotyped by GBS. The whole-genome variants were imputed, and 4,252,858 SNPs were obtained. Various molecular experiments were conducted to determine how the genes affected NM in pigs. Results: A strong GWAS peak located on SSC11: 0.10 to 7.11 Mbp (Top SNP, SSC11:1,889,658 bp; p = 9.98E-13) was identified in cyclin dependent kinase 8 (CDK8) gene, which plays a crucial role in embryonic retardation and lethality. Based on the molecular experiments, we found that Y-box binding protein 1 (YBX1) was a crucial transcription factor for CDK8, which mediated the effect of CDK8 in the proliferation of porcine ovarian granulosa cells via transforming growth factor beta/small mother against decapentaplegic signaling pathway, and, as a consequence, affected embryo quality, indicating that this pathway may be contributing to mummified fetal in pigs. Conclusion: A powerful imputation-based association study was performed to identify genes associated with NM in pigs. CDK8 was suggested as a functional gene for the proliferation of porcine ovarian granulosa cells, but further studies are required to determine causative mutations and the effect of loci on NM in pigs.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.1
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• pp.94-110
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• 2010

Objective : This study was performed to evaluate the effect of immune reaction inductive substances such as phorbol-myristate-acetate(PMA), lipopolysaccharide(LPS), dermato-phagoides pteronyssus crude extract(DPE), dinitrochloro-benzene(DNCB) and Cryptotympana pustulata(CP), the Cryptotympana pustulata extracting substance at simultaneously on the translocation of nuclear factor-kappa B(NF-${\kappa}B$) towards to the nucleus and the mRNA expression patterns of various cytokine genes in Human acute monocytic leukemia cell line(THP-1 cells), monocytes of human. Experiment : To analyze cytokine genes expression patterns, the RT-PCR method was used, measuring tumor necrosis factor(TNF)-$\alpha$ that had been secreted during cell culture in the ELISA method. The morphological change in the cell observed during THP-1 cell culture was observed using a scanning electron microscope (SEM) and the quantitative distribution in the cell NF-${\kappa}B$ was analyzed through immunocytochemistry and a confocal microscopy. Result : CP showed different influences onto the mRNA expression patterns of cytokine genes with PMA, LPS. DPE and DNCB according to the types of immune inductive substances in the THP-1 cells. The expressions of inter-leukin(IL)-10, interferon(INF)-$\gamma$, TNF-$\alpha$ and monocyte chemoattractantant protein(MCP)-1 induced by PMA were suppressed by CP while the expression of transforming growth factor(TGF)-$\beta$ was promoted. Regarding the secretion pattern of TNF-$\alpha$ according to PMA processing, its secretion amount was increased by CP concurrent processing, in case of processing CP onto PMA and LPS, We discovered that the secretion amount of TNF-$\alpha$ was increased. Upon processing PMA and LPS on the THP-1 cell strain at the same time or either additionally processing CP thereon, the movement increase towards the nucleus from the NF-${\kappa}B$ cell cytoplasm, a transcription factor was able to be observed. Conclusion : In this study, Cryptotympana pustulata extracting substance was confirmed that it had an influence on expression patterns of cytokine genes according to the actions of a variety kinds of immune reaction inductive substances processed on the monocyte THP-1 cell of humans. Therefore, additional studies as for the immune adjusting function of Cryptotympana pustulata are considered to be able to offer important materials for curing immune abnormal diseases such as atopy dermatitis afterward.

• Food Science of Animal Resources
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• v.32 no.3
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• pp.339-345
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• 2012

This experiment was carried out in order to separate bovine colostral whey protein from Imsil province and to test the effect of immunological activity on RAW 264.7 cells. The colostral whey protein contained TGF-${\beta}$ 7, 475 pg/g in total. We first tested the effect of the colostral whey protein on the proliferation of RAW 264.7 cells and it demonstrated cytotoxicity at concentrations greater than 20 mg/mL. Therefore, the immunological activities of colostral whey protein were investigated in maximum concentration of 10 mg/mL on LPS-induced RAW 264.7 cells. Results indicated that colostral whey protein inhibited the LPS-induced nitric oxide (NO) production in a dose-dependent manner. The colostral whey protein also suppressed the productions of proinflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in a dose-dependent manner. In addition to the immunological activity, colostral whey protein led to the expression of heme oxygenase-1 (HO-1) in RAW 264.7 cells. In conclusion, colostral whey protein containing TGF-${\beta}$ inhibited the production of NO, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 via expression of HO-1.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.425-434
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• 2013

UV irradiation is the main factor contributing to skin damages that are associated with an excessive production of matrix-degrading metalloproteinase (MMP)-1 and a deficient expression of collagens. To date, red ginseng has been revealed to possess many biomedical effects, such as anti-aging, anti-oxidation, and anti-inflammatory. In this study, we prepared the Korean Red Ginseng extracts treated with enzyme (KRGE) and investigated the effects of dietary KRGE on the formation of wrinkles generated by UVB irradiation in hairless mice. It was found that KRGE inhibited the UVB-induced formation of wrinkles, epidermal thickness, and skin dryness in hairless mice. Further results also showed that KRGE attenuated UVB-induced MMP-${\beta}$1 level, while accelerated procollagen type I, transforming growth factor-${\beta}$1 secretion. Interestingly, the expression of profilaggrin and filaggrin in both the epidermis and dermis were decreased due to UVB exposure and reversed by KRGE. The KRGE 0.06% was prior to KRGE 0.24%. In view of these results, which indicated that KRGE protected skin from UVB-induced photodamages, which may not only mediated by regulating of MMP-1 and procollagen type I, but also by increasing the production of profilaggrin and filaggrin. In conclusion, our results suggest that KRGE may be a promising agent for the treatment of skin photodamages. The challenge of KRGE will be expected as cosmeceuticals and nutraceuticals in order to intervene in aging-related degenerative skin changes.

• Archives of Craniofacial Surgery
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• v.18 no.1
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• pp.9-15
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• 2017

Background: Relaxin is a transforming growth factor ${\beta}1$ antagonist. To determine the effects of relaxin on scar reduction, we investigated the scar remodeling process by injecting relaxin-expressing adenoviruses using a pig scar model. Methods: Scars with full thickness were generated on the backs of Yorkshire pigs. Scars were divided into two groups (relaxin [RLX] and Control). Adenoviruses were injected into the RLX (expressing relaxin) and Control (not expressing relaxin) groups. Changes in the surface areas, color index and pliability of scars were compared. Results: Fifty days after treatment, the surface areas of scars decreased, the color of scars was normalized, and the pliability of scars increased in RLX group. Conclusion: Relaxin-expressing adenoviruses improved the surface area, color, and pliability of scars. The mechanism of therapeutic effects on scar formation should be further investigated.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.552-561
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• 2023

The endocrinology of type 2 diabetes (T2D) and its predisposing factors have been studied extensively while its skeletal effects have received negligible research despite this being a global disease. The cellular and molecular association between proximal humeral fractures and T2D has not been fully elucidated. We aimed to study bone cell quantities and immunolabel osteogenic and antiosteogenic cytokines. The study used 12-week-old rats (23 males) consisting of 8 Sprague Dawley (SD) and 15 Zucker Diabetic Sprague Dawley (ZDSD). Weekly mass measurements were taken while fasting blood glucose levels were recorded every 2 weeks with oral glucose tolerance tests conducted once every 4 weeks. Upon termination at the age of 28 weeks, humeri were fixed in 10% buffered formalin, prior to decalcification in ethylenediaminetetraacetic acid. The bone samples were then processed in ascending grades of alcohol using an automatic processor before embedding in paraffin wax. Sections were cut at 5 ㎛ thickness in a series for Haematoxylin and Eosin stain, and immunohistochemistry was performed with the anti-tartrate-resistant acid phosphatase (TRAP), anti-alkaline phosphatase (ALP), anti-bone morphogenetic protein 3 (BMP3), anti-transforming growth factor beta 1 (TGFβ1), anti-aged glycation end product (AGE) antibodies in the sequence. ZDSD rats had more adipocytes, BMP3 and AGEs expression with higher numbers of TRAP positive osteocytes and fewer ALP cells although no differences were found in TGFβ1 immunopositivity. We also found that T2D increases the number of AGEs immuno-positive cells, as well as its extracellular expression, thus providing a conducive environment for the interaction of the osteogenic cytokine and its antagonist to suppress osteoblastogenesis. ZDSD groups had higher adipocyte numbers therefore increased marrow adiposity in T2D.

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.1-14
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• 2003

Objective : The aim of the study was to investigate the preventive effect of Acanthopanax senticosus(AS) aqua-acupuncture into Sinsu(BL23) of the multiple low-does strepozotocin(STZ)-induced diabetic rats. Methods : The experimental animals were divided into 4 groups : normal group of rats, control group of multiple low-does STZ-induced diabetic rats, NSAA group with 0.4ml normal saline(NS) aqua-acupunctured subcutaneously into Sinsu in multiple low-does STZ-induced diabetic rats, and ASAA group with 0.4ml of 20% AS aqua-acupunctured subcutaneously into Sinsu in multiple low-does STZ-induced diabetic rats. Each of AS and NS aqua-acupuncture was done subcutaneously into both loci of Sinsu taking turns everyday for 3 weeks. Thereafter the levels of serum glucose, body weight, index of kidney hypertrophy, urine glucose, urinary albumin excretion, creatinine clearance, mesangial cell and TGF-${\beta}1$ expression in glomeruli and tubular cells were measured on the determined day. Conclusions : 1. Both ASAA and NSAA groups decreased the serum glucose levels in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group showed more significant decreases than NSAA group. 2. Both ASAA and NSAA groups prevented the development of diabetes in multiple low-dose STZ-induced diabetic rats as compared to the control group, and ASAA group prevented more markedly the development of diabetes than NSAA group. 3. Both ASAA and NSAA groups prevented the reduction of body weight in multiple low-dose STZ-induced diabetic rats as compared to the control group, and ASAA group showed the same as the normal group. 4. Both ASAA and NSAA groups did not show any changes of the creatinine clearance in multiple low-does STZ-induced diabetic rats. 5. Both ASAA and NSAA groups prevented the excretion of urinary glucose and albumin in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group showed more significant prevention than NSAA group. 6. Both ASAA and NSAA groups prevented the expansion of glomerular cells and the protein expression of transforming growth factor-${\beta}1$ in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group prevented more significantly than NSAA group.

• Journal of Veterinary Science
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• v.22 no.2
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• pp.16.1-16.13
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• 2021

Background: Preconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells. Objectives: This study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ). Methods: To assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs. Results: Pretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factor-beta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E₂ (PGE₂) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE₂ levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ. Conclusions: IFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE₂, which induces macrophage polarization and increases regulatory T-cell numbers.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.15-23
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• 2017

Objectives : It is well known that Sibjotang (Shizaotang), traditional herbal medicine formula, regulates the body fluid blood pressure homeostasis. This study is to investigate whether Sibjotang improves diabetic renal dysfunction in type II diabetes mellitus animal model, db/db mice. Methods : The animals model were divided into three groups at the age of 8 weeks; control group (C57BLKS/J-db/m mice), diabetic group [(C57BLKS/J+Lepr)-db/db mice], and Sibjotang group [(C57BLKS/J+Lepr)-db/db mice + Sibjotang 100 mg/kg/day]. During 8 weeks of treatment, blood glucose and urinary albumin excretion were checked in metabolic chamber at 8, 12, and 16 weeks of age, respectively. Results : Body weight and food intake of diabetic group were significantly higher than control group after 8 weeks administration. However, there were not significant different between the diabetic group and Sibjotang group. Urinary albumin excretion was significantly decreased in the Sibjotang group than the diabetic group. In addition, supplementation with Sibjotang significantly lowered levels of blood glucose, insulin, and homeostatic model assessment-insulin resistance (HOMA-IR), suggesting reduced insulin resistance. The ratio of mesangial matrix/glomerular area was markedly larger in diabetic group than control group, whereas Sibjotang significantly reduced this expansion. Moreover, immunohistological study revealed that Sibjotang attenuated the increase of transforming growth $factor(TGF)-{\beta}$ expression in kidney. Conclusion : Sibjotang ameliorates diabetes-associated renal injury through the improvement of the blood glucose and insulin sensitivity, and inhibiting the $TGF-{\beta}1$ expression. Therefore, Sibjotang may be a new therapeutic formula for the treatment of diabetic-associated renal dysfunction.