• The Korean Journal of Physiology and Pharmacology
• /
• 제19권4호
• /
• pp.365-372
• /
• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• Archives of Plastic Surgery
• /
• 제37권4호
• /
• pp.469-472
• /
• 2010

Purpose: Aplasia Cutis Congenita (ACC) is a rare disease characterized by the focal defect of the skin at birth, frequently involving scalp, but it may affect any region of the body. There are no etiology known but some conditions such as intrauterine vascular ischemia, amniotic adherences and viral infections are associated. The ideal treatment for the ACC is not known. Superficial and relatively small sized defects (< $3{\times}5\;cm$) may heal spontaneously and large defects related with risks of infection and bleeding may require aggressive surgical treatment. Hyalomatrix$^{(R)}$ is a bilayer of an esterified hyaluronan scaffold beneath a silicone membrane. It has been used as a temporary dermal substitute to cover deep thickness skin defect and has physiological functions derive from the structural role in extracellular matrix and interaction with cell surface receptor. This material has been used for the wound bed pre-treatment for skin graft to follow and especially in uncooperative patient, like a newborn, this could be a efficient and aseptic way of promoting granulation without daily irritative wound care. For this reason, using Hyalomatrix$^{(R)}$ for the treatment of ACC was preferred in this paper. Methods: We report a case of a newborn with ACC of the vertex scalp and non-ossified partial skull defect. The large sized skin and skull defect ($6{\times}6\;cm$) was found with intact dura mater. No other complications such as bleeding or abnormal neurologic sign were accompanied. Escharectomy was performed and Hyalomatrix$^{(R)}$ was applied for the protection and the induction of acute wound healing for 3 months before the split-thickness skin graft. During the 3 months period, the dressing was renewed in aseptic technique for every 3 weeks. The skin graft was achieved on the healthy granulation bed. Results: The operative procedure was uneventful without necessity of blood transfusion. Postoperative physical examination revealed no additional abnormalities. Regular wound management was performed in out-patient clinic and the grafted skin was taken completely. No other problems developed during follow-up. Conclusion: Hyalomatrix$^{(R)}$ provides protective and favorable environment for wound healing. The combination of the use of Hyalomatrix$^{(R)}$ and the skin graft will be a good alternative for the ACC patients with relatively large defect on vertex.

• 동의생리병리학회지
• /
• 제21권3호
• /
• pp.700-704
• /
• 2007

In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Here we investigated the role of the extract of Anethi Fructus in the expression of inflammatory mediators, surface molecule, and related receptors in vitro. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Anethi Fructus increased the production of secretary tumor necrosis factor (TNF)-a and Nitric oxide (NO), and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. The water extract of Anethi Fructus increased the production of interferon (IFN)-g from splenocytes. Also, water extract of Anethi Fructus increased ConA-induced cell proliferation. These results suggest that water extract of Anethi Fructus may enhance the immune response through immune modulation of macrophage and lymphocytes.

• 한국식품위생안전성학회지
• /
• 제21권4호
• /
• pp.197-203
• /
• 2006

Parabens are most wildly used in food, cosmetics and pharmaceutic products as preservatives caused of safety and cheap. we had examined that paraben had estrogenic activity through the in vivo and in vitro experiments in last year. We demonstrated that most of parabens(ethyl, butyl, propyl, isobutyl, isopropyl) increased significantly uterus weight as well as induced proliferation of MCF-7 cell and binding of estrogen receptor as endocrine disrupter compounds. In this study, we evaluated that whether parabens have effect on male reproductive system or not. the male rats were administrated parabens by oral injection then examined separation of preputial day for $PND23\simPND52$. As the results, most parabens delayed pubertal development compare to control group. The separation of preputial day of Butyl and Propyl parabens at high concentration were PND 44 days and PND 45days compared to control group as PND 40 days. Even though, parabens as endocrine disrupter wildly spread in food, cosmetics and pharmaceutic products, we didn't have the safe guideline. In abroad, they are re-evaluating safety assessment for parabens. In conclusion, parabens delayed pubertal development in juvenile parabens are consider as endocrine disrupter chemicals.

• 대한치과마취과학회지
• /
• 제14권2호
• /
• pp.101-106
• /
• 2014

Background: Remifentanil, an ultra-short-acting mu-opioid receptor agonist, is unique from other opioids because of its esterase-based metabolism, minimal accumulation, and very rapid onset and offset of clinical action. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. However, the effects of remifentanil on human keratinocyte and autophagy have yet to be fully elucidated during hypoxia-reoxygenation. Here we investigated whether remifentanil confers protective effect against hypoxia-reoxygenation in human keratinocyte and, if so, whether autophagy mediates this effect. Methods: The human keratinocytes were cultured under 1% oxygen tension. The cells were gassed with 94% $N_2$, and 5% $CO_2$ and incubated for 24 h at $37^{\circ}C$. To determine whether the administration of affects human keratinocytes hypoxia-reoxygenation injury, cells were then exposed to various concentrations of remifentanil (0.01, 0.1, 0.5 and 1 ng/ml) for 2 h. After remifentanil treatment, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. Control group did not receive remifentanil treatment. Normoxia group did not receive hypoxia and remifentanil treatment for 36 h. 3-MA group was treated 3-methyladenine (3-MA) for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with MTT, showing the mitochondrial activity of living cells. Cells were stained with fluorescence and analyzed with Western blot analysis to find out any relations with activation of autophagy. Results: Prominent accumulation of autophagic specific staining MDC was observed around the nuclei in RPT group HaCaT cells. Similarly, AO staining, red fluorescent spots appeared in RPT group HaCaT cells, while the Normoxia, control and 3-MA groups showed mainly green cytoplasmic fluorescence. We here examined activation of autophagy related protein under H/R-induced cells by Western blotting analysis. Atg5, Beclin-1, LC3-II (microtubule-associated protein 1 light chain 3 form II) and p62 was elevated in RPT group cells. But they were decreased when autophagy was suppressed by 3-MA (Fig. 5). Conclusions: Although the findings of this study are limited to an in vitro interpretation, we suggest that remifentanil may have a beneficial effect in the recovery of wound from hypoxia-reoxygenation injury.

• 한국키틴키토산학회지
• /
• 제23권4호
• /
• pp.277-284
• /
• 2018

본 연구에서는 제주 자생해조류인 감태로부터 제조한 ethyl acetate 분획물의 비만 세포에 대한 항알러지 활성에 관한 연구를 수행하였다. IgE/BSA로 활성화시킨 비만 세포에서 EC-EtoAc는 세포 독성 없이 비만 세포의 탈과립 지표로 사용되는 ${\beta}$-hexosaminidase의 분비 뿐만 아니라 알러지 유발성 케모카인(TARC)과 사이토카인(IL-$1{\beta}$, IL-4, IL-6, IL-10, IL-13, IFN-${\gamma}$ 및 TNF-${\alpha}$)의 mRNA 발현을 억제하였다. 또한, EC-EtoAc는 비만 세포의 표면 리셉터인 $Fc{\varepsilon}RI$의 발현 및 IgE와 $Fc{\varepsilon}RI$의 결합능을 감소시켰다. 이 모든 결과로부터, 감태 유래 분획물인 EC-EtoAc가 활성화된 비만 세포에서 $Fc{\varepsilon}RI$의 발현 및 IgE와 $Fc{\varepsilon}RI$의 결합능을 감소시킴으로써 알러지 유발성 매개 인자들의 분비와 발현 등을 감소시켜 항알러지 효능을 가진다는 것을 알 수 있었다. 또한, 이 연구 결과는 EC-EtoAc가 항알러지 효능을 보이는 천연 소재로서 이용가치가 있다는 것을 제시한다.

• 생명과학회지
• /
• 제31권10호
• /
• pp.873-884
• /
• 2021

본 연구에서는 다양한 인체 암포주를 대상으로 NSAID의 항암 효과를 증강시키는 artesunate (ART)의 역할과 이에 대한 분자적 기전을 연구하였다. 다양한 타입의 암세포주를 대상으로 암세포 성장 억제 활성을 조사한 결과, ART는 NSAID인 celecoxib (CCB) 또는 dimethyl-CCB (DMC)와의 병용 효과를 나타내었다. ART 처리로 ATF4/CHOP의 발현 증강과 함께 오토파지 유도 표식인 p62 감소의 결과로서, ATF4/CHOP 경로가 ART의 오토파지 유도 활성에 관여할 것으로 예상되었으며, ART의 오토파지 활성과 관련하여 NRF2 및 암 줄기 세포 관련 단백질인 CD44, CD133, ALDH1, Oct4, mutated p53 (mutp53) 및 c-Myc의 발현이 감소되었다. 또한 DMC 단독처리 보다 ART와 DMC의 병용으로 ATF4/CHOP의 발현 증강과 p62의 감소가 더욱 촉진되고, NRF2 및 암 줄기 세포 관련 단백질 발현 감소도 현저히 촉진되면서 궁극적으로 PARP 활성화에 의해 apoptosis가 유도됨을 알 수 있었다. 이러한 결과는 ART/DMC 병용 처리가 각 물질 단독 처리보다 암세포의 성장 억제 및 apoptosis 유도에 더욱 효과적이고, ART 및 DMC 의 오토파지 유도 활성은 암 줄기 세포 관련 단백질의 분해를 촉진함으로써, 암 줄기 세포가 제거될 수 있음을 시사하였다. 이와 같이 ART는 NSAID 뿐만 아니라 imatinib의 항암 효과를 증강시키는 활성으로, chemosensitizer로서 중요한 후보 물질이 될 수 있음을 밝혔다.

• 한국가금학회지
• /
• 제48권3호
• /
• pp.111-122
• /
• 2021

최근에 IL-34가 MCSFR에 대한 두 번째 기능적 리간드로 확인되었으며, M-CSFR에 대한 결합을 통해 IL-34는 M-CSF와 유사한 기능을 공유한다. 지금까지 닭의 IL-34에 대한 실험적 연구가 아닌 예측된 서열로만 보고되었으며, 닭의 IL-34 기능에 대한 정보는 아직 부족하다. 닭 IL-34의 잠재적 생물학적 기능을 구명하기 위하여, 다양한 품종의 닭, 세포주에 대한 괴사성 장염, 살모넬라 및 E. coli 유래의 LPS 등을 처리하여 관찰하였다. 또한 닭의 IL-34와 M-CSF 재조합 단백질 생산 및 이를 이용한 전염증성 사이토카인 유도를 위하여 클로닝 및 재조합 단백질을 발현 및 정제하였다. 특히 관절이상 육계(unknown cause)에 대한 IL-34, M-CSF, 그리고 M-CSFR 유전자의 발현이 대조구보다 유의하게 증가하였으나, 병원균 자극 조직의 경우 많은 조직에서 감소함을 보였다. M-CSFR의 발현은 in vitro에서 IL-34와 M-CSF 재조합 단백질에 의해 증가함을 보였으며, IFN-γ은 재조합 단백질 M-CSF을 제외한 IL-34에 의해 증가하였다. 하지만, IL-12 발현은 유의적인 차이가 없었으며, IL-1β의 경우는 감소하였다. 이 결과는 IL-34와 M-CSF가 고전적인 대식세포와 대체 대식세포 모두에서 역할을 한다고 할 수 있다. 결론적으로, in vitro와 in vivo 실험을 통하여 병원균 처리 시 닭의 IL-34 발현을 관찰하였으며, IL-34 재조합 단백질이 대식세포에서와 전염증성과 항염증성 반응에 중요한 역할을 함을 증명하였다. 추후에 IL-34의 사이토카인, 케모카인 그리고 염증반응 경로 등에 대한 추가 연구가 필요하다고 판단된다.

• Journal of Animal Science and Technology
• /
• 제63권4호
• /
• pp.934-953
• /
• 2021

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

• 생명과학회지
• /
• 제29권4호
• /
• pp.447-454
• /
• 2019

비만은 에너지의 불균형으로 인하여 체내 지방조직에 지방이 축적되는 대사성질환으로 심혈관계 질환, 고혈압, 2형 당뇨, 고지혈증 및 각종 암의 발생 빈도를 증가시키는 요인이다. 지방의 축적은 지방전구세포가 지방세포로 분화하는 과정을 의미하는 adipogenesis라는 과정을 거쳐서 일어난다. 지방세포로의 분화는 다양한 호르몬과 전사인자들의 상호작용에 의해서 일어난다. 본 연구에서는 팔각회향이 항비만 소재로 활용 가능한지 확인하기 위해, 팔각회향 물 추출물을 분획하여 지방축적 억제 활성이 좋은 dichloromethane층을 선정하였다. 3T3-L1 지방전구세포가 성숙한 지방세포로 분화할 때 팔각회향 dichloromethane 층이 어떠한 기전으로 분화를 조절하는지 확인한 결과, 지방세포 분화에서 중요한 전사인자인 C/EBP family, $PPAR{\gamma}$의 발현이 억제되었고, 지방세포 최종 분화 마커로 알려져 있는 FAS 및 LPL의 발현 또한 감소되었다. 또한 G1기에서의 세포주기 정지를 통해 지방세포 분화 단계에서 필수적인 mitotic clonal expansion 단계를 억제한다는 결과를 얻었다. 이러한 연구 결과는 팔각회향이 항비만 효과를 가지는 천연물 소재로의 활용가능성을 보여주는 기초 자료가 될 것으로 사료된다.