• Journal of Korean Neurosurgical Society
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• 제65권5호
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• pp.680-687
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• 2022

Objective : The influence of moderate-to-severe traumatic brain injury (TBI) on acute pulmonary injury is well established, but the association between acute pulmonary injury and mild TBI has not been well studied. Here, we evaluated the histological changes and fluctuations in inflammatory markers in the lungs to determine whether an acute pulmonary inflammatory response occurred after mild TBI. Methods : Mouse models of mild TBI (n=24) were induced via open-head injuries using a stereotaxic impactor. The brain and lungs were examined 6, 24, and 72 hours after injury and compared to sham-operated controls (n=24). Fluoro-Jade B staining and Astra blue and hematoxylin staining were performed to assess cerebral neuronal degeneration and pulmonary histological architecture. Quantitative real-time polymerase chain reaction analysis was done to measure inflammatory cytokines. Results : Increased neuronal degeneration and the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were observed after mild TBI. The IL-6, TNF-α, and TGF-β levels in mice with mild TBI were significantly different compared to those of sham-operated mice 24 hours after injury, and this was more pronounced at 72 hours. Mild TBI induced acute pulmonary interstitial edema with cell infiltration and alveolar morphological changes. In particular, a significant infiltration of mast cells was observed. Among the inflammatory cytokines, TNF-α was significantly increased in the lungs at 6 hours, but there was no significant difference 24 and 72 hours after injury. Conclusion : Mild TBI induced acute pulmonary interstitial inflammation and alveolar structural changes, which are likely to worsen the patient's prognosis.

• Journal of Microbiology and Biotechnology
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• 제33권3호
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• pp.339-347
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• 2023

Transforming growth factor-β is a key factor in regulating adhesion formation during tendon healing. We investigated the effectiveness of SMAD family members, SMAD7 and SMAD3, in the TGF-β/Smad signaling during flexor tendon repair. Mouse flexor toe deep tendon rupture anastomosis models were made. On days 3, 7, 14, 21, and 28, the expressions of smad7 and smad3 in flexor tendon tissues were detected by RT-qPCR and western blot. Furthermore, postoperative intraperitoneal injections of SMAD7 agonists or SMAD3 antagonists were given. The degree of tendon healing was evaluated by adhesion testing and biomechanical experiments. Hematoxylin and eosin (HE) staining was used to observe the pathological changes. Immunohistochemistry was used to evaluate the expressions of collagen III, SMAD3, and SMAD7. The mRNA levels of matrix metalloproteinases, Mmp2 and Mmp9, and scleraxis (SCX) in flexor tendon tissue were detected by RT-qPCR. Smad3 expression increased and Smad7 expression decreased in flexor tendon tissue after injury. In addition, the SMAD7 agonist blocked SMAD3 phosphorylation. SMAD7 agonist and SMAD3 antagonist both improved adhesion formation during flexor tendon healing, and decreased the expressions of collagen III, Mmp9, and SCX, while increasing Mmp2 expression. This study provides a possible theoretical basis for the SMAD7-SMAD3 signal cascade during flexor tendon adhesion healing.

• Nutrition Research and Practice
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• 제17권2호
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• pp.206-217
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• 2023

BACKGROUND/OBJECTIVES: The immunomodulatory effect of Platycodon grandiflorum (PG) has been reported, but studies on its mechanism are still lacking. This study was undertaken to confirm whether the hydrolyzed and fermented PG extract (HFPGE) obtained by adding hydrolysis and fermentation to the extraction process has an immune-enhancing effect in the in vivo system. MATERIALS/METHODS: Five-week-old BALB/c mice were divided into 4 groups: normal control group (NOR), control group (CON), 150 mg/kg body weight (BW)/day HFPGE-treated group (T150), and 300 mg/kg BW/day HFPGE-treated group (T300). The mice were administered HFPGE for 4 weeks and intraperitoneally injected with cyclophosphamide (CPA, 80 mg/kg BW/day) on day 6, 7, and 8, respectively, to induce immunosuppression. The levels of immunoglobulins (Igs) and cytokines were measured in the serum. In splenocytes, proliferation and cytokine levels were measured. RESULTS: Serum IgA, IgG, and IgM levels were observed to decrease after CPA treatment, which was recovered by HFPGE administration. The levels of serum interleukin (IL)-12, tumor necrosis factor (TNF)-α, IL-8, and transforming growth factor (TGF)-β were also decreased after exposure to CPA but increased after HFPGE administration. Decreased splenocyte proliferation was seen in CPA-treated mice, but was observed to increase in the T150 and T300 groups as compared to the NOR group. Compared to the CON group, splenocyte proliferation stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the HFPGE-treated groups was significantly increased. The cytokines secreted by ConA-stimulated splenocytes (IL-2, IL-12, interferon-γ, TNF-α) were increased in the T150 and T300 groups, and cytokines secreted by LPS-stimulated splenocytes (IL-4, IL-8, TGF-β) were also increased by HFPGE administration. CONCLUSION: These results suggest that HFPGE stimulates the immunity in immunosuppressed conditions, thereby enhancing the immune response. Therefore, it is expected that HFPGE has the potential to be used as functional food and medicine for immune recovery in various immunocompromised situations.

• Fisheries and Aquatic Sciences
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• 제26권6호
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• pp.406-422
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• 2023

Sarcopenia is an age-related, progressive skeletal muscle disorder involving the loss of muscle mass and strength. Previous studies have shown that γ-aminobutyric acid (GABA) from fermented oysters aids in regulatory T cells (Tregs) cell expansion and function by enhancing autophagy, and concomitantly mediate muscle regeneration by modulating muscle inflammation and satellite cell function. The fermentation process of oysters not only increases the GABA content but also enhances the content of branched amino acids and free amino acids that aid the level of protein absorption and muscle strength, mass, and repair. In this study, the effect of GABA-enriched fermented sarco oyster extract (FSO) on reduced muscle mass and functions via Treg modulation and enhanced autophagy in aged mice was investigated. Results showed that FSO enhanced the expression of autophagy markers (autophagy-related gene 5 [ATG5] and GABA receptor-associated protein [GABARAP]), forkhead box protein 3 (FoxP3) expression, and levels of anti-inflammatory cytokines (interleukin [IL]-10 and transforming growth factor [TGF]-β) secreted by Tregs while reducing pro-inflammatory cytokine levels (IL-17A and interferon [IFN]-γ). Furthermore, FSO increased the expression of IL-33 and its receptor IL-1 receptor-like 1 (ST2); well-known signaling pathways that increase amphiregulin (Areg) secretion and expression of myogenesis markers (myogenic factor 5, myoblast determination protein 1, and myogenin). Muscle mass and function were also enhanced via FSO. Overall, the current study suggests that FSO increased autophagy, which enhanced Treg accumulation and function, decreased muscle inflammation, and increased satellite cell function for muscle regeneration and therefore could decrease the loss of muscle mass and function with aging.

• 한국어류학회지
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• 제26권3호
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• pp.171-178
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• 2014

로즈마리의 주요 성분인 carnosic acid는 carnosol, rosmarinic acid, ursolic acid 등과 같은 폴리페놀의 한 성분으로 다양한 생리활성 기능이 보고되어 있다. 본 연구에서는 로즈마리 유래 폴리페놀인 carnosic acid가 제브라피쉬 근육성장에 미치는 영향을 근육 내 주사와 사료를 통해서 확인해 보았다. 근육 내 주사 실험을 통해서 CA는 제브라 피쉬의 근육 내 단백질 함량을 증가시키고 중성지방의 함량을 감소시켰다. 또한 조직학적 분석 결과 근섬유의 평균 면적이 커지는 근섬유의 과비대 효과를 나타내었다. 사료 실험 결과 근육 내 단백질 및 중성지방의 함량에는 영향을 미치지 않았으며 조직학적 분석 결과 근육 내 주사 실험에서와 마찬가지로 근 섬유의 과비대를 유도하였다.

• Journal of Oral Medicine and Pain
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• 제40권3호
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• pp.110-114
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• 2015

Purpose: Growth and differentiation factor (GDF)-11 is a transforming growth factor-${\beta}$ family member that plays important regulatory roles in development of multiple tissues which include axial skeletal patterning, palatal closure, and tooth formation. Proteins that have been identified as GDF-11 inhibitors include GDF-associated serum protein (GASP)-1 and GASP-2. Recently, we found that mice genetically engineered to lack both Gasp1 and Gdf11 have an increased frequency of cleft palate. The goal of this study was to investigate the roles of GDF-11 and its inhibitors, GASP-1 and GASP-2, during dental and craniofacial development and growth. Methods: Mouse genetic studies were used in this study. Homozygous knockout mice for Gasp1 ($Gasp1^{-/-}$) and Gasp2 ($Gasp2^{-/-}$) were viable and fertile, but Gdf11 homozygous knockout ($Gdf11^{-/-}$) mice died within 24 hours after birth. The effect of either Gasp1 or Gasp2 deletion in $Gdf11^{-/-}$ mice during embryogenesis was evaluated in $Gasp1^{-/-}$;$Gdf11^{-/-}$ and $Gasp2^{-/-}$;$Gdf11^{-/-}$ mouse embryos at 18.5 days post-coitum (E18.5). For the analysis of adult tissues, we used $Gasp1^{-/-}$;$Gdf11^{+/-}$ and $Gasp2^{-/-}$;$Gdf11^{+/-}$ mice to evaluate the potential haploinsufficiency of Gdf11 in $Gasp1^{-/-}$ and $Gasp2^{-/-}$ mice. Results: Although Gasp2 expression decreased after E10.5, Gasp1 expression was readily detected in various ectodermal tissues at E17.5, including hair follicles, epithelium in nasal cavity, retina, and developing tooth buds. Interestingly, $Gasp1^{-/-}$;$Gdf11^{-/-}$ mice had abnormal formation of lower incisors: tooth buds for lower incisors were under-developed or missing. Although $Gdf11^{+/-}$ mice were viable and had mild transformations of the axial skeleton, no specific defects in the craniofacial development have been observed in $Gdf11^{+/-}$ mice. However, loss of Gasp1 in $Gdf11^{+/-}$ mice occasionally resulted in small and abnormally shaped auricles. Conclusions: These findings suggest that both GASP-1 and GDF-11 play important roles in dental and craniofacial development both during embryogenesis and in adult tissues.

• 한국식품영양과학회지
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• 제43권3호
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• pp.374-380
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• 2014

본 연구에서는 야관문 추출물의 마우스 대식세포에 대한 항염증 활성과 창상유발 동물실험 모델을 통한 창상치유 효과를 조사하였다. RAW264.7 세포에서 야관문 추출물은 0.2 mg/mL 이하 농도에서 세포생존에 영향을 주지 않았으며, 염증반응이 활성화된 대식세포에 대해 농도 의존적으로 유의적인 NO 생성 감소를 나타내었다. 창상유발 동물실험 모델에서 야관문 추출물을 함유한 화장품 조성물의 창상치유효과에 대해 육안적으로 관찰한 결과, SCO군과 CCO군보다 야관문 추출물을 함유한 SSP군에서 약 20~30% 빠른 상처면적 감소 효과를 나타내었으며, 반흔 크기 역시 약 12% 작게 형성되었다. 또한 SSP군 조직의 외피와 진피 재생회복속도가 빨라진 것을 Masson's trichrome 염색을 통해 확인할 수 있었으며, VEGF 및 TGF-${\beta}1$ 유전자 발현이 SCO군과 비교 시 각각 감소 및 증가하였다. 이러한 결과는 야관문 추출물이 항염증 및 교원질 생성 유도를 통한 조직재생 활성에 기여하여 창상치유 속도를 가속화하고 반흔 면적을 감소시킬 수 있는 피부 창상치유와 관련한 코스메슈티컬 소재로써 산업적 활용이 가능함을 보여준다.

• Journal of Periodontal and Implant Science
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• 제31권4호
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• pp.787-801
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• 2001

The molecular mechanisms control the function of PDL(periodonta1 ligament) cells and/or fibroblasts remain unclear. PDLsl7, PDL-specific gene, had previousely　identified the cDNA for a novel protein from cultured　PDL fibroblasts using subtraction hybridization between gingival fibroblasts and　PDL fibroblasts. The purpose　of this study was to determine the regulation by growth factors and cytokines on　PDLsl7 gene expression in　cultured human periodontal ligament cells and observe the immunohistochemical　localization of PDLsl7 protein in various tissues of mouse. Primary PDL fibroblasts isolated by scraping the root of the extracted human mandibular third molars. The cells were incubated with various concentration of human recombinant $IL-1{\beta}$, PDGF-BB and TGF\;${\beta}$ for 48h nd 2 weeks. At each time point total RNA was extracted and the levels of transcription ere assessed by reverse transcription-polymerase chain reaction (RT-PCR assay). polyclonal antiserum raised against PDLsl7 peptides, CLSVSYNRSYQINE and SEAVHETDLHDGC, were made, and stained the tooth, periodontium, developing bone, bone marrow and mid-palatal suture of the mouse. The results were as follows. 1. PDLsl7 mRNA levels were increased in response to PDGF (10ng/ml) and $TGF\;{\beta}$(20ng/ml) after treatment of the $IL-1{\beta}$, PDGF-BB and $TGF{\beta}$for 48 h. 2. PDLsl7 was up-regulated only by $TGF{\beta}$(20 ng/ml) after treatment of the $IL-1{\beta}$, PDGF-BB and $TGF\;{\beta}$ for 2 weeks and unchanged by the other stimulants. 3. PDLsl7 was a novel protein coding the 142 amino acid peptides in the ORF and the nucleotide sequences of the obtained cDNA from RT-PCR was exactly same as the nucleotides of the database. 4. Immunohistochemical analysis showed that PDLsl7 is preferentially expressed in the PDL, differentiating osteoblast-like cells and stromal cells of the bone marrow in the adult mouse. 5. The expression of PDLsl7 protein was barely detectable in gingival fibroblasts, hematopoetic cells of the bone marrow and mature osteocytes of the alveolar bone. These results suggest that PDLsl7 might upregulated by PDGF-BB or $TGF{\beta}$ and acts at the initial stage of differentiation when the undifferentiated mesenchymal cells in the bone marrow and PDL differentiate into multiple cell types. However, more research needs to be performed to gain a better understanding of the exact function of PDLsl7 during the differentiation of bone marrow mesenchymal and PDL cells.

• Journal of Korean Neurosurgical Society
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• 제47권1호
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• pp.30-35
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• 2010

Objective: The purpose of this study is to explain the effect and reciprocal action among tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor-$\beta1$ (TGF-$\beta1$) on degeneration of human intervertebral disc (IVD). Methods: Human intervertebral disc tissues and cells were cultured with Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DMEM/F-12) media in $37^{\circ}C$, 5% $CO_2$ incubator. When IVD tissues were cultured with TWEAK, Fn14 that is an antagonistic receptor for TWEAK and TGF-$\beta1$, the level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay and sex determining region Y (SRY)-box 9 (Sox9) and versican messenger ribonucleic acid (mRNA) levels were estimated by reverse transcriptase polymerase chain reaction (RT-PCR). Results: When human IVD tissue was cultured for nine days, the sGAG content was elevated in proportion to culture duration. The sGAG was decreased significantly by TWEAK 100 ng/mL, however, Fn14 500 ng/mL did not change the sGAG production of IVD tissue. The Fn14 increased versican and Sox9 mRNA levels decreased with TWEAK in IVD tissue TGF-$\beta1$ 20 ng/mL elevated the sGAG concentration 40% more than control. The sGAG amount decreased with TWEAK was increased with Fn14 or TGF-$\beta1$ but the result was insignificant statistically. TGF-$\beta1$ increased the Sox9 mRNA expression to 180% compared to control group in IVD tissue. Sox9 and versican mRNA levels decreased by TWEAK were increased with TGF-$\beta1$ in primary cultured IVD cells, however, Fn14 did not show increasing effect on Sox9 and versican. Conclusion: This study suggests that TWEAK would act a role in intervertebral disc degeneration through decreasing sGAG and the mRNA level of versican and Sox9.

• Journal of Veterinary Science
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• 제22권2호
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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.