• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2093-2097
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• 2016

Background: HCV is a major global health problem. IL-27 is a member of the IL-6/IL-12 cytokine family with a broad range of anti-inflammatory properties. Recent studies highlighted the effect of a SNP in the IL-27 promoter region on modulating the progression of infectious diseases and individual responses to therapy. Aim of the work: The present study investigated the potential role of (-964 A/G) SNP in the promoter region of IL-27p28 gene (alleles rs153109) on the outcome of HCV infection among genotype 4a infected patients. Materials and Methods: HCV genotyping confirmed that all of the HCV-infected patients had genotype 4a infection. Genomic DNA was extracted from 111 patients with chronic HCV infection, 42 spontaneous resolvers (SR) and 16 healthy controls. IL- 27p28.rs153109 genotyping was assessed using PCR-RFLP then confirmed by DNA sequencing. Results: The frequency of IL-27-p28.rs153109AA, AG, and GG genotypes among chronically infected subjects were 74.8 %, 25.2%, and 0% while among the SR, they were 57.1%, 35.7%, and 7.14%, respectively. Our data show the unique presence of G/G genotype in the SR group (3 patients; 7.14%). Moreover, the "G" allele frequencies among chronic and resolved subjects were 12.6% and 25.0%, respectively (p=0.0136). Importantly, subjects with the GG genotype were more likely to clear their HCV infection than those with the AA genotype (p=0.0118). Conclusions: HCV genotype 4a subjects with the IL-27-p28.rs153109 A/G and G/G genotype were more likely to clear their HCV infection. Therefore, we propose IL- 27p28.rs153109SNPas a genetic biomarker for predicting HCV infection outcome.

• Journal of Chest Surgery
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• 제26권6호
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• pp.475-482
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• 1993

90 patients[75 men and 15 women] with the thoracic disease underwent video-assisted thoracic surgery[VATS] during the period March 1992 to February 1993. The thoracic diseases were classified into two groups of spontaneous pneumothorax and general thoracic patients and they were 66 and 24, respectively.The mean size of the tumor resected was 4.3 $\pm$ 2.0 cm x 3.3 $\pm$ 1.1 cm x 2.7 $\pm$ 1.0 cm. The mean time of anesthesia and operation were 90.0 $\pm$ 19.9 min and 43.7 $\pm$ 13.1 min in spontaneous pneumothorax group and 123.3 $\pm$ 40.3 min and 62.8 $\pm$ 32.2 min in general thoracic group. The mean period of postoperative chest tube drainage and hospital stay were 5.0$\pm$ 5.5 days and 6.6 $\pm$ 7.4 days in spontaneous pneumothorax group and 3.5$\pm$ 1.6 days and 9.5 $\pm$ 6.1 days in general thoracic group. The indications of VATS were 71 pleural disease[78.9%: 66 spontaneous pneumothorax; 3 pleural effusions ; 1 pleural paragonimus westermanii cyst; 1 malignant pleural tumor with metastasis to the lung], 9 mediastinal disease[10.0%: 5 benign neurogenic tumor; 2 pericardial cyst; 1 benign cystic teratoma; 1 undifferentiated carcinoma], 8 pulmonary parenchymal disease[8.9%: 3 infectious disease ; 3 interstitial disease ; 2 malignant tumor ], and 2 traumatic cases of exploration and removal of hematoma[2.2%]. The applicated objectives of VATS were diagnostic[ 7 ], therapeutic[ 67 ] and both[ 16 ] and the performed procedures were pleurodesis[ 66 ], wedge resection of lung[ 59 ], parietal pleurectomy[ 11 ], removal of benign tumor[ 9 ], excision and/or biopsy of tumor[ 4 ], pleural biopsy and aspiration of pleural fluid[ 3 ] and exploration of hemothorax and removal of hematoma in traumatic 2 patients. The complication rate was 24.2%[ 16/66 ] in the spontaneous pneumothorax group and 8.3%[ 2/24 ] in the general thoracic group and so overally 20.0%[ 18/90 ]. The mortality within postoperative 30 days was 2.2%[ 2/90 ], including 1 acute renal failure and 1 respiratory failure due to rapid progression of pneumonia. The conversion rate to open thoracotomy during VATS was 5.6%[ 5/90 ], including 2 immediate postoperative massive air leakage, 1 giant bullae, 1 malignant pleural tumor with metastasis to lung and 1 pulmonary malignancy. The successful cure rate of VATS was 75.8%[ 50/66 ] in the spontaneous pneumothorax group and 76.5%[ 13/17 ] in the general thoracic group and the successful diagnostic rate was 100%[ 7/7 ]. In conclusion, although prospective trials should be progressed to define the precise role of VATS, the VATS carries a low morbidity and mortality and high diagnostic and therapeutic success rate and now can be effectively applicated to the surgical treatment of the extensive thoracic disease.

• 한국식품위생안전성학회지
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• 제31권1호
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• pp.59-66
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• 2016

Celastrol은 미역줄나무의 뿌리에서 얻은 추출물로 오래전부터 관절염 및 자가면역 같은 염증반응 질병들을 치료하기 위하여 쓰여져 왔다. 이외에도 많은 연구들에서 celastrol이 신경보호, 항산화 및 알츠하이머 치료에 사용될 수 있으며 특히, 암 치료에 효과적이라고 밝혀 졌다(Table 1). 따라서 많은 연구자들이 생리학적, 생화학적 및 면역학적 관점에서 celastrol의 항암효과를 규명하고자 노력을 기울이고 있으며, 다양한 관점에서 신호전달체계를 조절한다는 사실을 밝혀냈다(Fig. 1). 특히, celastrol은 $NF-{\kappa}B$를 억제함으로서 암의 발달 및 전이를 저해함을 물론, 암의 치료에 동반되는 면역 반응을 조절 할 수 있다(Fig. 2). 또한 세포사멸과 관계된 유전자들을 활성화 시키고, 항세포사멸 유전자들을 억제시킴으로서 세포 주기를 조절한다. 유전자 조절 외에도 heat shock protein과 같은 단백질의 변조와 자가소화작용(autophagy)를 유도한다. 이처럼 celastrol의 다양한 효과는 암의 성공적 치료에 한발 더 가까워지게 만든다. 이외에도 celastrol의 항 비만 효과가 알려지면서 향후 비만 및 비만과 연계된 암 환자들이 가질 수 있는 부작용, 오남용 및 비용절감 측면에서 좋은 결과를 나타낼 것이라 예상 된다. Celastrol의 다양한 기작이 밝혀짐에도 불구 하고 직접적인 결합 부위에 대한 연구 결과는 아직 없으며, 임상적용 하기에 앞서 다양한 동물모델 in vivo 실험이 필요하다. 또한 임상치료 시도에 있어 안전성을 확보 하기 위해서는 celastrol의 단기간 및 장기간의 효과에 대한 깊은 연구가 요구된다.

• Childhood Kidney Diseases
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• 제7권1호
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• pp.9-15
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• 2003

목적 : PAN-induced nephrosis 쥐 모델에서 HMG-CoA reductase inhibitor로 작용하여 콜레스테롤을 낮추는 약제로 알려진 atorvastatin을 투여함으로써, 지질대사에 대한 효과와 지질대사의 변화가 쥐 모델의 신장 변화에 미치는 영향을 알아보고자 하였다. 대상 및 방법 : 수컷 Sprague-Dawley 흰쥐를 사용하여 대조군(I군), PAN 단독 투여군(II군), PAN과 atrovastatin 동시 투여군(III군) 3군으로 나누었으며, PAN은 체중 100 gm 당 2 mg을 첫 피하 주사한 후 1, 3, 5, 7, 9주에 반복하여 피하 주사하였으며, atorvastatin은 체중 100 gm당 5 mg을 물에 녹여 매일 경구 투여하였다. 실험 개시 후 11주에 24시간 소변과 혈액을 채취한 다음 신장을 적출 하였으며, 소변의 protein과 creatinine 그리고 혈청의 albumin, BUN, creatinine, lipid profiles를 측정하고, 신장의 형태학적 변화를 관찰하였다. 결과 : 혈청 총 콜레스테롤은 II군이 $291{\pm}173\;mg/dL$, III군이 $167{\pm}72\;mg/dL$, LDL은 II군이 $57{\pm}53\;mg/dL$, III군이 $27{\pm}12\;mg/dL$로 II군 보다 III군에서 감소하였으나 통계학적으로 유의하지는 않았다. 광학 현미경 검사상 사구체 경화의 빈도는 II군이 26.2%, III군이 13.3%로 II군보다 III군에서 적게 나타났다. 결론 : Atorvastatin을 puromycin과 같이 투여한 경우 총 콜레스테롤과 LDL을 낮추었으며 사구체 경화의 빈도도 감소시킨 것으로 보아 고지혈증이 사구체 경화성 변화에 중요한 원인 중의 하나로 생각된다.

• 한국안광학회지
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• 제17권4호
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• pp.395-401
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• 2012

목적: 발효자색고구마와 블루베리(blueberry)에서 추출한 안토시아닌의 시력보호 및 VDT 증후군 개선효과를 알아보고자 연구하였다. 방법: 실험은 안과질환 및 전신질환이 없고, 굴절이상이 -4.00 D 이상인 19~21세 남 여 20명을 대상으로 실시하였다. 40 mg의 발효자색고구마 및 블루베리 추출 안토시아닌과 대조군으로 위약을 각각 복용, 2시간 후에 근업(VDT)을 2시간 동안 실시하였다. 시력검사는 안토시아닌을 복용하기 전과 2시간 근업 후 각각 타각적 굴절검사 방법으로 측정하였다. 근업 2시간 후 VDT 증후군으로 두통, 안통 및 안정피로, 목, 어깨, 허리 등의 자각증상의 정도를 심함, 보통, 약간, 없음 등으로 구분하여 문진하였다. 결과: 2시간동안 VDT 작업 후 시력보호 효과는 우위안에 대한 굴절 값은 발효 자색고구마 추출 안토시아닌에서는 $0.031{\pm}0.21$ D, 블루베리 추출 안토시아닌에서는 $0.006{\pm}0.32$ D 만큼 근시도가 감소하였고, 위약에서는 $0.144{\pm}0.28$ D(t=2.27, p=0.03) 만큼 유의하게 근시도가 증가하였다. 결론: 발효자색고구마 추출 안토시아닌이 근업 후 굴절이상 값의 증가를 억제하고, 비우위안보다 우위 안에서 시력을 보호하는 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.219-228
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• 2015

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.

• The Korean Journal of Physiology and Pharmacology
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• 제17권3호
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• pp.203-208
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• 2013

As the abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a critical role in the development of atherosclerosis and vascular restenosis, a candidate drug with antiproliferative properties is needed. We investigated the antiproliferative action and underlying mechanism of a newly synthesized naphthoquinone derivative, 5,8-dimethoxy-2-nonylamino-naphthalene-1,4-dione (2-nonylamino-DMNQ), using VSMCs treated with platelet-derived growth factor (PDGF). 2-Nonylamino-DMNQ inhibited proliferation and cell number of VSMCs induced by PDGF, but not epidermal growth factor (EGF), in a concentration-dependent manner without any cytotoxicity. This derivative suppressed PDGF-induced $[^3H]$-thymidine incorporation, cell cycle progression from $G_0/G_1$ to S phase, and the phosphorylation of phosphor-retinoblastoma protein (pRb) as well as the expression of cyclin E/D, cyclin-dependent kinase (CDK) 2/4, and proliferating cell nuclear antigen (PCNA). Importantly, 2-nonylamino-DMNQ inhibited the phosphorylation of PDGF receptor${\beta}$(PDGF-$R{\beta}$) enhanced by PDGF at $Tyr^{579}$, $Tyr^{716}$, $Tyr^{751}$, and $Tyr^{1021}$ residues. Subsequently, 2-nonylamino-DMNQ inhibited PDGF-induced phosphorylation of STAT3, ERK1/2, Akt, and $PLC{\gamma}1$. Therefore, our results indicate that 2-nonylamino-DMNQ inhibits PDGF-induced VSMC proliferation by blocking PDGF-$R{\beta}$ autophosphorylation, and subsequently PDGF-$R{\beta}$-mediated downstream signaling pathways.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.437-442
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• 2020

Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

• 정신신체의학
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• 제29권2호
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• pp.77-85
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• 2021

유방암은 여성에서 가장 높은 유병율을 보이는 암으로, 진단과 치료과정 및 치료 후에도 다양한 정신사회적 디스트레스가 자주 나타난다. 유방암 환자의 치료에는 의학적 치료뿐만 아니라 정신신체의학적 통합치료가 필요하다. 유방암 환자는 스트레스, 불안장애, 우울장애, 적응 장애 등에 대한 취약성이 증가하고, 이러한 정신장애는 유방암의 악화 또는 재발과 연관이 있다. 유방암 환자의 불안과 우울에 대한 정신사회적 치료는 환자의 삶의 질을 증진시키고, 유방암의 재발과 악화를 감소시킨다. 본 연구에서는 5편의 유방암 치료 가이드라인에서 정신사회적 디스트레스에 대한 정신사회적 치료와 대체의학적 치료가 포함된 정신신체의학적 통합치료 부분에 초점을 맞추어 논의하였다. 5편의 가이드 라인에서 사용한 서로 다른 근거 기준은 US Preventive Service Task Force (USPSTF) 기준에 맞춰 연구자들이 평가하여 근거를 기술하였다. 또한 유방암 환자의 불안, 우울, 기분, 삶의 질에 대한 정신사회적 치료의 효과 크기를 요약하였고, 정신신체의학적 통합치료 서비스 제공에 대한 장벽과 이에 대한 대안을 제시하였다. 다학제 팀을 구성하고, 환자 요구도를 조사하며, 정신사회적 치료의 정보를 환자에게 제공하여 환자와 가족이 참여하는 것이 중요하다. 또한 준비된 계획에 따라 정기적으로 정신사회적 디스트레스를 평가하고, 정신신체의학 전문가 또는 자문조정 정신건강의학과 의사에 의한 정신신체의학적 통합치료가 환자에게 제공되는 것이 가장 중요하다.

• Journal of Clinical Nutrition
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• 제10권2호
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• pp.45-50
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• 2018

Purpose: Intense multidisciplinary team effort is required for the intestinal rehabilitation of patients afflicted with the short bowel syndrome (SBS). These include enteral and parenteral nutrition (PN) support, monitoring of complications related to treatment, and considering further medical or surgical options for intestinal adaptation. Methods: In the Intestinal Rehabilitation Team (IRT) at the Samsung Medical Center, we have experienced 20 cases of adult SBS requiring multidisciplinary intestinal rehabilitation. This study is a retrospective review of the collected medical records. Results: Of the 20 subjects treated, 12 patients were male and 8 patients were female. At the time of referral to the IRT, the mean age was 51.5 years, and the mean body weight was 50.1 kg, which was 90% of the usual body weight. The diseases or operative managements preceding massive bowel resection were malignancy in 11 cases, cardiac surgery in 2 cases, trauma in 2 cases and one case, each of tuberculosis, corrosive esophagitis, atrial fibrillation, simultaneous pancreas and kidney transplantation, and perforated appendicitis. Of these, there were 14 survivals and 6 mortalities. The fatalities were attributed to progression of disease, intestinal failure-associated liver disease, and sepsis (unrelated to intestinal failure) (2 cases each). Among the 14 surviving patients, 8 patients have been weaned off PN, whereas 6 are still dependent on PN (mean PN dependence 36%). Conclusion: This paper reports the results of multidisciplinary intestinal rehabilitation of adult short bowel patients treated at the Samsung Medical Center. Further studies are required to improve survival and enteral tolerance of these patients.