• Biomolecules & Therapeutics
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• 제28권1호
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• pp.98-103
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• 2020

Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 (Fbn1) gene, has vascular manifestations including aortic aneurysm, dissection, and rupture. Its vascular pathogenesis is assumed to be attributed to increased transforming growth factor β (TGFβ) signaling and blockade of excessive TGFβ signaling has been thought to prevent dissection and aneurysm formation. Here, we investigated whether galunisertib, a potent small-molecule inhibitor of TGFβ receptor I (TβRI), attenuates aneurysmal disease in a murine model of MFS (Fbn1^C1039G/+) and compared the impact of galuninsertib on the MFS-related vascular pathogenesis with that of losartan, a prophylactic agent routinely used for patients with MFS. Fbn1^C1039G/+ mice were administered galunisertib or losartan for 8 weeks, and their ascending aortas were assessed for histopathological changes and phosphorylation of Smad2 and extracellular signal-regulated kinase 1/2 (Erk1/2). Mice treated with galunisertib or losartan barely exhibited phosphorylated Smad2, suggesting that both drugs effectively blocked overactivated canonical TGFβ signaling in Fbn1^C1039G/+ mice. However, galunisertib treatment did not attenuate disrupted medial wall architecture and only partially decreased Erk1/2 phosphorylation, whereas losartan significantly inhibited MFS-associated aortopathy and markedly decreased Erk1/2 phosphorylation in Fbn1^C1039G/+ mice. These data unexpectedly revealed that galunisertib, a TβRI inhibitor, showed no benefits in aneurysmal disease in MFS mice although it completely blocked Smad2 phosphorylation. The significant losartan-induced inhibition of both aortic vascular pathogenesis and Smad2 phosphorylation implied that canonical TGFβ signaling might not prominently drive aneurysmal diseases in MFS mice.

• 한국어병학회지
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• 제21권2호
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• pp.119-127
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• 2008

Oxytetracycline (OTC) has been widely used in eel culture as a therapeutic and prophylactic agent because of its broad-spectrum activity against gram-positive and -negative bacteria. The oral treatment dosage of OTC approved for the treatment of edwardsiellosis, furunculosis and vibriosis in eel is 50 mg/kg/day for 3-7 days in Korea. To determine new optimum dose of OTC in eel, the pharmacokinetics of OTC after single oral administration (100 mg/kg B.W., 200 mg/kg B.W.) in cultured eel, Anguilla japonica was examined. In oral dosage of 100 and 200 mg/kg body weight, the highest plasma concentrations of OTC were 1.19±0.42 ㎍/㎖ and 2.69±0.57 ㎍/㎖, respectively. Plasma concentrations of OTC were not detected after 720 h post-dose in all experiments. The kinetic profile of absorption, distribution and elimination of OTC in plasma wwas calculated fitting to a 1- and 2-compartment model by WinNonlin program. The following parameters were obtained for a single dosage of 100 and 200 mg/kg respectively: 1-compartment model, AUC= 82.48 and 432.68 ㎍*h/㎖, Tmax= 3.93 and 14.24 hr, Cmax= 0.94 and 2.34 ㎕/㎖; 2-compartment model, AUC= 448.73 and 530.65 ㎍*h/㎖, Tmax= 6.37 and 8.96 hr, Cmax= 0.90 and 3.21 ㎕/㎖.

• 대한한의학방제학회지
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• 제29권4호
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• pp.191-203
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• 2021

Objectives : In this study, we investigate the anti-allergic effects of Ullmus macrocarpa Hance (Ulmus) on RBL-2H3 mast cell (basophilic leukemia cell line), which are mediated by FcεRIs. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in IgE-antigen-mediated RBL-2H3 cells. Cell toxicity was determined by MTT assay and the markers of degranulation such as beta-hexosaminidase, histamine, PGD2, TNF-α, IL-4, IL-6 production of inflammatory mediators and FcεRI-mediated protein expression by western blot. Results : Ulmus inhibited degranulation and production of allergic mediators (e.g., TNF-α, IL-4, and IL-6) in them. Ulmus reduced histamine levels, expression of FcεRI signaling-related genes such as Lyn, Syk, and Fyn, and extracellular signal-regulated kinase phosphorylation in mast cells. Also, Ulmus reduced PGD2 release and cyclooxygenase-2 expression, and cytosolic phospholipase A2 phosphorylation in FcεRI-mediated RBL-2H3 mast cells. Conclusions : These results indicate that Ulmus exhibits anti-allergic activity through inhibition of degranulation and inflammatory mediators and cytokine release. These findings suggest that Ulmus may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

• Ocean and Polar Research
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• 제44권1호
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• pp.61-67
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• 2022

In this study, in order to evaluate the anti-obesity effect of sargassum horneri extract, the effects of the extract on lipase activity and preadipocyte differentiation in 3T3-L1 cells were investigated. S. horneri extract between 0.0 and 1.0 mg/mL showed no cytotoxicity and inhibited lipase activity by 68.1%. When S. horneri extract was utilized at levels of 0.25, 0.5, and 1.0 mg/mL in 3T3-L1 cells, preadipocytes differentiation decreased by 11.4, 19.7, and 25.6%, respectively, showing anti-obesity effects. In addition, after treatment with 1.0 mg/mL S. horneri extract, the mRNA expression levels of sterol regulatory element binding proteins-1c (SREBP-1c), peroxisome proliferator activated receptor-γ (PPAR-γ), CCAAT enhancer binding protein-α (CEBP-α), fatty acid synthase (FAS), and stearoyl-CoA desaturase1 (SCD1) in 3T3-L1 cells were significantly decreased (p < 0.05) by 65.2, 54.9, 50.0, 33.8, and 33.8% respectively. These results showed that S. horneri extract suppresses lipase activity and prophylactic preadipocyte differentiation in 3T3-L1, and thus can be used as an anti-obesity agent in functional foods and medicines.

• 대한본초학회지
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• 제28권6호
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• pp.135-143
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• 2013

Objectives : The purpose of this study was to determine whether the methanol extract of Cassia mimosoides var. nomame Makino, a naturally growing plant in Korea, could prevent the renal-ischemia/reperfusion injury in a rat model or not. Methods : The radical scavenging activities of the extracts, and ascorbic acid as a positive control, were measured in vitro. At one hour after an intraperitoneal injection of the extract (400 mg/kg), renal ischemia/reperfusion injury was generated by 40 min clamping of the left renal artery in rats. After renal ischemia/reperfusion and 24 hr restoration of blood circulation, the serum creatinine concentration was measured. And the extent of epithelial cell injury and apoptosis was assessed by various staining technologies. The Bax/Bcl-2 ratio and activated caspase-3 were assessed by immunohistochemistry. Results : The extract showed a slightly lower level of radical scavenging activity than that of ascorbic acid. Compared to those of the vehicle-treated group, the extract-treated group displayed a significantly smaller tubular epithelial cell injury of 54% reduction in the outer medulla region and a lower serum creatinine concentration of 50% reduction. It seems that the reduction in cellular injury is due to the attenuation of the Bax/Bcl-2 ratio, and the inhibition of caspase-3 activation by the extract of Cassia mimosoides. Conclusions : Cassia mimosoides var. nomame Makino could be a good candidate for a prophylactic agent against the ischemia/reperfusion/induced kidney injury.

• Journal of Ginseng Research
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• 제47권6호
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• pp.706-713
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• 2023

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B₂ secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP₃R). In the presence of G-Rk3, dense tubular system Ca²⁺ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β₃ and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA₂. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

• 대한한의학방제학회지
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• 제31권4호
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• pp.315-325
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• 2023

Objectives : Recently, research has been actively conducted on the efficacy of complexes based on oriental medicine prescriptions for improving immune activity and allergies. In this study, In this study, we aimed to examine the effect of Angelica gigas Nakai and Corni fructus extract (AC), medicinal herbs, among candidate drugs derived through preliminary experiments with various components of oriental medicine prescriptions for allergies, on allergies in RBL-2H3 cells. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in anti-DNP-IgE activated DNP-HSA in RBL-2H3 cells. Cell toxicity was determined by WST-1 assay and the markers of degranulation such as beta-hexosaminidase, histamine, TNF-α and IL-6 production of inflammatory mediators and FcεRI-mediated expression. Results : The results showed that treatment with AC extract (20, 40 and 80㎍/㎖) noncytotoxic levels and significantly inhibited the release of β-hexosaminidase, histamine and the production of TNF-α and IL-6 in RBL-2H3 by the antigen stimulation. Conclusions : These results indicate that AC extract exhibits anti-allergic activity through inhibition of degranulation and inhibition of inflammatory mediators and cytokine release. These findings suggest that AC extract may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.221-226
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• 2023

혈소판의 적절한 활성화와 응집이 필요하지만 과도하거나 비정상적인 응집은 뇌졸중, 혈전증, 동맥경화증과 같은 심혈관 질환을 유발할 수 있다. 따라서 이러한 질병을 예방하고 치료하기 위해서는 혈소판 응집을 조절하거나 억제할 수 있는 물질을 찾는 것이 중요하다. 여러 연구에서 Panax 인삼의 특정 ginsenoside 화합물이 혈소판 응집을 억제할 수 있음이 알려져 있다. 이들 화합물 중 Panax ginseng의 Rk3 (G-Rk3)는 혈소판 응집 억제의 기전이 불확실 하기에 이를 밝히기 위한 연구가 필요하다. G-Rk3는 cAMP의 양을 강하게 증가시켰고 cAMP 의존성 kinase의 기질인 VASP 및 IP3R의 인산화를 유도했다. 또한, G-Rk3의 효과는 PI3K/Akt 인산화의 억제를 일으켜 세포 내 과립의 분비를 감소시켰다. 궁극적으로 G-Rk3는 혈소판 응집을 효과적으로 억제하였다. 따라서 우리는 과도한 혈소판 응집으로 인한 심혈관 질환의 예방 또는 치료제로서의 G-Rk3의 가능성을 제안한다.

• 대한본초학회지
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• 제29권3호
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• pp.11-17
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• 2014

Objective : Portulaca oleracea (PO) has been used as an important traditional medicine for inflammatory and bacterial diseases in East Asia. However, the protective effects of PO on acute pancreatitis (AP) is not well-known. Therefore, this study was performed to identify the anti-inflammatory and prophylactic effects of PO on cerulein-induced AP. Methods : AP was induced in mice via intraperitoneal injection of supramaximal concentrations of the stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) given every hour for 6 times. Water extracts of PO (100, 300, or 500 mg/kg) was administrated intra-peritoneally 1 h prior to the first injection of cerulein. The mice were killed at 6 h after the final cerulein injection. Pancreas and lung were rapidly removed for morphologic and histochemical examination, myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activities. Results : Administration of PO significantly inhibited pancreatic weight/body weight ratio, pancreas and lung histological injury. And MPO activity which indicates neutrophil infiltration was inhibited by PO extracts on cerulein-induced pancreatitis. In addition, PO administration inhibited digestive enzymes such as serum amylase and lipase activity on cerulein-induced pancreatitis. Conclusion : Our results could suggest that pre-treatment of PO reduces the severity of cerulein-induced AP, thereby, PO could be used as a protective agent against AP. Also, this study could give a clinical basis that PO could be a drug or agent to prevent AP.

• Pediatric Infection and Vaccine
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• 제7권2호
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• pp.225-232
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• 2000

목 적 : 올바른 항생제의 사용을 위해서는 우선 항생제 사용 실태의 파악과 함께 검사실의 확충, 의료진의 협조 등 다양한 노력과 보완이 요구된다. 본 연구는 적절한 항생제 사용의 기반을 마련하고자 현재 시행되고 있는 항생제 사용 실태를 조사하였다. 방 법 : 전북대학교병원에 입원한 환자 총 1,833명을 대상으로 의무기록을 통하여 항생제의 사용 여부, 종류, 사용 기간, 용량, 항생제의 투약 시작 시기 및 투여 목적을 조사하였다. 결 과 : 전체 조사 대상 환자 1,833명 중 입원 기간 중 항생제를 사용한 환자는 1,231명으로 67.2%였으며, 계별로 살펴보면 내과계는 전체 1,014명 중 497명(49.0%)이 항생제를 사용하였고, 외과계는 819명 중 734명(89.6%)에서 항생제를 사용하였다. 전체 항생제를 사용한 환자 1,231명 중 706명(57.4%)에서 예방 목적으로 사용하였고, 525명(42.6%)에서 치료 목적으로 사용하였다. 항생제를 사용한 환자의 경우 사용된 항생제의 갯수를 살펴보면 총 1,231명 중 1가지 항생제를 사용한 경우는 125명(10.2%)이었으며, 2가지를 사용한 경우는 311명(25.3%), 3가지를 사용한 경우는 562명(45.6%), 4가지 이상을 사용한 경우는 233명(18.9%)으로, 70% 이상의 환자에서 3가지 이상의 항생제가 사용하였다. 사용 항생제의 종류는 ${\beta}$-lactam, aminoglycoside, quinolone, macrolide, 항진균제, metronidazole, clindamycin, trimethoprim-sulfamethoxazole, glycopeptide, 그리고 fosfomycin 등으로 아주 다양하였다. 전체적인 그룹별 사용률을 보면 ${\beta}$-lactam은 57.0%, aminoglycoside는 34.5%, quinolone은 3.6% 그리고 기타 그룹은 4.9%로, ${\beta}$-lactam과 aminoglycoside가 가장 많이 사용되었다. 결 론 : 대부분의 환자에서 2가지 이상의 항생제의 병합요법이 보편화되어 있다는 점은 진지하게 검토되어야 할 것으로 생각된다. 아울러 임상적으로 전신 세균 감염이 확실한 경우에도 원인 병원체를 찾아내기 위한 적극적인 노력이 부족한 경우도 상당수 있어 이에 대해서도 검사실과 함께 적극적인 개선의 노력이 필요할 것으로 생각된다. 수술 환자의 예방적 화학 요법에 대해서도 개선이 필요할 것으로 생각된다.