Apocynin abrogates methotrexate-induced nephrotoxicity: role of TLR4/NF-κB-p65/p38-MAPK, IL-6/STAT-3, PPAR-γ, and SIRT1/FOXO3 signaling pathways

Emad H. M. Hassanein,Ahmed M. Sayed,Omnia A. M. Abd El-Ghafar,Zainab M. M. Omar,Eman K. Rashwan,Zuhair M. Mohammedsaleh,So Young Kyung,Jae Hyeon Park,Hyung Sik Kim,Fares E. M. Ali 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.4

The present study was designed to evaluate the potential renoprotective impacts of apocynin (APC) against nephrotoxicity induced by methotrexate (MTX) administration. To fulfill this aim, rats were allocated into four groups: control; APC (100 mg/kg/day; orally); MTX (20 mg/kg; single intraperitoneal dose at the end of the 5th day of the experiment); and APC +MTX (APC was given orally for 5 days before and 5 days after induction of renal toxicity by MTX). On the 11th day, samples were collected to estimate kidney function biomarkers, oxidative stress, pro-inflammatory cytokines, and other molecular targets. Compared to the MTX control group, treatment with APC significantly decreased urea, creatinine, and KIM-1 levels and improved kidney histological alterations. Furthermore, APC restored oxidant/antioxidant balance, as evidenced by a remarkable alleviation of MDA, GSH, SOD, and MPO levels. Additionally, the iNOS, NO, p-NF-κB-p65, Ace-NF-κB-p65, TLR4, p-p38-MAPK, p-JAK1, and p-STAT-3 expressions were reduced, while the IκBα, PPAR-γ, SIRT1, and FOXO3 expressions were significantly increased. In NRK-52E cells, MTX-induced cytotoxicity was protected by APC in a concentration-dependent manner. In addition, increased expression of p-STAT-3 and p-JAK1/2 levels were reduced in MTX-treated NRK-52E cells by APC. The in vitro experiments revealed that APC-protected MTX-mediated renal tubular epithelial cells were damaged by inhibiting the JAK/STAT3 pathway. Besides, our in vivo and in vitro results were confirmed by predicting computational pharmacology results using molecular docking and network pharmacology analysis. In conclusion, our findings proved that APC could be a good candidate for MTX-induced renal damage due to its strong antioxidative and anti-inflammatory bioactivities.

Endobronchial ALK-Positive Anaplastic Large Cell Lymphoma Presenting Massive Hemoptysis

Kim, Hee Kyung,Kim, Bo Hye,Kim, Sae Ahm,Shin, Jae Kyoung,Song, Ji-Hyun,Kwon, Ah-Young,Kim, Jung-Hyun,Kim, Eun-Kyung,Lee, Ji-Hyun,Kim, Gwaung-Il,Jeong, Hye Cheol The Korean Academy of Tuberculosis and Respiratory 2015 Tuberculosis and Respiratory Diseases Vol.78 No.4

Primary anaplastic large cell lymphoma (ALCL) of the lung is highly aggressive and quite rare. We report here a case of anaplastic lymphoma kinase-positive endobronchial ALCL, that was initially thought to be primary lung cancer. A 68-year-old woman presented with hemoptysis, dyspnea, and upper respiratory symptoms persisting since 1 month. The hemoptysis and and bronchial obstruction lead to respiratory failure, prompting emergency radiotherapy and steroid treatment based on the probable diagnosis of lung cancer, although a biopsy did not confirm malignancy. Following treatment, her symptoms resolved completely. Chest computed tomography scan performed 8 months later showed increased and enlarged intra-abdominal lymph nodes, suggesting lymphoma. At that time, a lymph node biopsy was recommended, but the patient refused and was lost to follow up. Sixteen months later, the patient revisited the emergency department, complaining of persistent abdominal pain since several months. A laparoscopic intra-abdominal lymph node biopsy confirmed a diagnosis of ALCL.

제대혈의 적혈구 제거 방법에 관한 연구 : 제대혈 은행 설립을 위한 기초 연구 Basic Study for the Establishment of Cord Blood Bank

김효정,서철원,김상희,김상위,김성배,김강욱,조화정,민영주,박진희,김암,이인식,이필량,지현숙,서종진,강위창,이정신,김우건 대한조혈모세포이식학회 2000 대한조혈모세포이식학회지 Vol.5 No.1

배경:제대혈에서 적혈구를 제거하는 것은 제대혈 은행의 효율적인 운영 및 제대혈이식시 ABO 부적합 수혈, DMSO 독성 등의 부작용을 해결하기 위한 이상적인 방법이다. 저자들은 동일한 제대혈로 여러가지 적혈구 제거법을 동시에 시행하여, 이들에서 CD34양성 세포의 수득률 및 조혈세포 집락형성능을 비교하여 제대혈 은행 설립의 기반 기술을 확립하고자 하였다. 방법:제왕절개 직후 헤파린 처리된 용기에 제대혈을 채취하였다. 제대혈은 5개의 용기에 분산하여 실온에서 보관하였고 12시간 이내에 적혈구를 분리하였다. 적혈구 제거 방법으로 Ficoll 비중 분리법, gelatin 침전법, 적혈구 용혈법, starch 침전법을 각각의 제대혈에서 시행하였다. 전혈과 적혈구가 제거된 제대혈에서의 세포 생존율, 적혈구 제거율과 단핵구 및 CD34양성 세포의 수득률, 조혈세포 집락형성능을 비교 분석하였다. 결과:18례에서의 평균 제대혈 채취양은 81.3 mL(범위 42~128 mL)이었다. 서로 다른 적혈구 제거법들간에 세포 생존률과 적혈구 제거율은 차이가 없었다. 단핵구 수득률은 3% gelatin침전법(47.7±14.5%)이 다른 적혈구 제거법보다 유의하게 높았다. 3% gelatin침전법은 Ficoll비중 분리법과 Starch침전법에 비해 CD34 양성 세포수가 통계적으로 유의하게 높았다(36.1±5.4×10³/mL, 15.0±3.5×10³/mL, 20.7±4.2×10³/mL). 또한 CFC의 집락수도 3% gelatin침전법에서 Ficoll 비중 분리법과 적혈구 용혈법에 비해 우수한 결과를 보였다(52.0±7.1×10²/mL, 32.8±4.7×10²/mL, 36.8±5.7×10²/mL). 그러나 제대혈 전혈의 CD34 양성 세포수(65.7±11.2×10³/mL) 및 CFC의 집락수(117.8±15.8×10²/mL)를 적혈구 제거법을 이용한 실험군과 비교하였을 때 전혈군에서 높은 것을 알 수 있었다. 결론:3% gelatin 침전법은 다른 적혈구 제거법과 비교해 볼 때 더 우수한 단핵구, CD34 양성 세포 수득률 및 조혈세포 집락형성능을 보였다. 그러나 다른 보고들과는 달리 3% gelatin 침전법은 CD34양성 세포 및 CFC 집락수의 절대값이 제대혈 전혈과 비교하여 의미있게 낮았다. 이러한 결과는 시약의 종류와 실험방법의 차이에 기인하는 것으로 사료되며, 최상의 세포 수득률을 얻기 위하여 적혈구 분리 방법의 표준화를 위한 연구가 진행되어야 할 것으로 생각된다. Background:Efficient volume reduction is important to make a cost-effective umbilical cord blood (UCB) banking system. The aim of this study was to find a method of red cell depletion of UCB without major losses of the hematopoietic progenitor-CD34+ cells. Methods:Eighteen cord blood samples were collected in heparinized bottle immediately after Cesarean section. Five aliquots of each cord blood were stored at room temperature and processed within 12 hours. We used 4 different RBC depletion methods (Ficoll density gradient separation, gelatin sedimentation, red cell lysis, starch sedimentation) and compared the results of viability, RBC reduction rate, mononuclear cell (MNC) recovery rate, CD34+ cells and colony forming unit (CFC).Results: The mean collected cord blood volume was 81.3 mL (range 42~128 mL). There were no differences of viability and RBC reduction rate among groups. MNC recovery rate were significantly higher in gelatin group (47.7±14.5%) than other RBC depletion methods. Gelatin group had significantly higher CD34+ cell count than Ficoll and starch group (36.1±5.4×10³/mL, 15.0±3.5×10³/mL, 20.7±4.2×10³/mL) and higher CFC count than Ficoll and RBC lysis group (52.0±7.1×10²/mL, 32.8±4.7×10²/mL, 36.8±5.7×10²/mL). But the results of CD34+ cell count (65.7±11.2×10³/mL) and CFC count (117.8±15.8×10²/mL) of untreated control group are significantly higher than those of all other treated groups. Conclusion:Umbilical cord blood processed with 3% gelatin sedimentation has higher recovery rate of MNC, CD34+, cell and CFC than other groups. Unlike other reports, the absolute numbers of CD34+ cell and CFC count of 3% gelatin sedimentation method are significantly lower than those of untreated control group. Different laboratory processes with gelatin could be one cause of these differences, a study for standardized laboratory methods should be established to obtain higher recovery rate of hematopoietic cells after RBC depletion.

CASE REPORT : Endobronchial ALK-Positive Anaplastic Large Cell Lymphoma Presenting Massive Hemoptysis

( Hee Kyung Kim ),( Bo Hye Kim ),( Sae Ahm Kim ),( Jae Kyoung Shin ),( Ji Hyun Song ),( Ah Young Kwon ),( Jung Hyun Kim ),( Eun Kyung Kim ),( Ji Hyun Lee ),( Gwaung Il Kim ),( Hye Cheol Jeong ) 대한결핵 및 호흡기학회 2015 Tuberculosis and Respiratory Diseases Vol.78 No.4

Primary anaplastic large cell lymphoma (ALCL) of the lung is highly aggressive and quite rare. We report here a case of anaplastic lymphoma kinase-positive endobronchial ALCL, that was initially thought to be primary lung cancer. A 68-year-old woman presented with hemoptysis, dyspnea, and upper respiratory symptoms persisting since 1 month. The hemoptysis and and bronchial obstruction lead to respiratory failure, prompting emergency radiotherapy and steroid treatment based on the probable diagnosis of lung cancer, although a biopsy did not confirm malignancy. Following treatment, her symptoms resolved completely. Chest computed tomography scan performed 8 months later showed increased and enlarged intra-abdominal lymph nodes, suggesting lymphoma. At that time, a lymph node biopsy was recommended, but the patient refused and was lost to follow up. Sixteen months later, the patient revisited the emergency department, complaining of persistent abdominal pain since several months. A laparoscopic intra-abdominal lymph node biopsy confirmed a diagnosis of ALCL.

Incidence and Clinical Characteristics of Congenital Cardiac Anomaly in Korea

위지선 (Ji Sun We ),Bo Hyun Yoon,Ahm Kim,Jong Hwa Kim,Yong Kyon Jo,Yong Ju Kim,Moon Young Kim,Suk Young Kim,Sung Soo Kim,Young Woo Kim,Byung In Kim,Jong Chul Shin 대한산부인과학회 2008 대한산부인과학회 학술대회 Vol.94 No.-

Outcome of Inhaler Withdrawal in Patients Receiving Triple Therapy for COPD

Kim, Sae Ahm,Lee, Ji-Hyun,Kim, Eun-Kyung,Kim, Tae-Hyung,Kim, Woo Jin,Lee, Jin Hwa,Yoon, Ho Il,Baek, Seunghee,Lee, Jae Seung,Oh, Yeon-Mok,Lee, Sang-Do The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.1

Background: The purpose of this study was to document outcomes following withdrawal of a single inhaler (step-down) in chronic obstructive pulmonary disease (COPD) patients on triple therapy (long-acting muscarinic antagonist and a combination of long-acting ${\beta}2$-agonists and inhaled corticosteroid), which a common treatment strategy in clinical practice. Methods: Through a retrospective observational study, COPD patients receiving triple therapy over 2 years (triple group; n=109) were compared with those who had undergone triple therapy for at least 1 year and subsequently, over 9 months, initiated inhaler withdrawal (step-down group, n=39). The index time was defined as the time of withdrawal in the step-down group and as 1 year after the start of triple therapy in the triple group. Results: Lung function at the index time was superior and the previous exacerbation frequency was lower in the step-down group than in the triple group. Step-down resulted in aggravating disease symptoms, a reduced overall quality of life, decreasing exercise performance, and accelerated forced expiratory volume in 1 second ($FEV_1$) decline ($54.7{\pm}15.7mL/yr$ vs. $10.7{\pm}7.1mL/yr$, p=0.007), but there was no observed increase in the frequency of exacerbations. Conclusion: Withdrawal of a single inhaler during triple therapy in COPD patients should be conducted with caution as it may impair the exercise capacity and quality of life while accelerating $FEV_1$ decline.

Nanotherapeutics of PTEN Inhibitor with Mesoporous Silica Nanocarrier Effective for Axonal Outgrowth of Adult Neurons

Kim, Min Soo,El-Fiqi, Ahmed,Kim, Jong-Wan,Ahn, Hong-Sun,Kim, Hyukmin,Son, Young-Jin,Kim, Hae-Won,Hyun, Jung Keun American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.29

<P>Development of therapeutic strategies such as effective drug delivery is an urgent and yet unmet need for repair of damaged nervous systems. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) regulates axonal regrowth of central and peripheral nervous systems; its inhibition, meanwhile, facilitates axonal outgrowth of injured neurons. Here we show that nanotherapeutics based on mesoporous silica nanoparticles loading PTEN-inhibitor bisperoxovanadium (BpV) are effective for delivery of drug molecules and consequent improvement of axonal outgrowth. Mesoporous nanocarriers loaded BpV drug at large amount (27 mu g per 1 mg of carrier), and released sustainably over 10 d. Nanocarrier-BpV treatment of primary neurons from the dorsal root ganglions (DRGs) of rats and mice at various concentrations induced them to actively take up the nanocomplexes with an uptake efficiency as high as 85%. The nanocomplex-administered neurons exhibited significantly enhanced axonal outgrowth compared with those treated with free-BpV drug. The expression of a series of proteins involved in PTEN inhibition and downstream signaling was substantially up-/down-regulated by the nanocarrier-BpV system. Injection of the nanocarriers into neural tissues (DRG, brain cortex, and spinal cord), moreover, demonstrated successful integration into neurons, glial cells, oligodendrocytes, and macrophages, suggesting the possible nanotherapeutics applications in vivo. Together, PTEN-inhibitor delivery via mesoporous nanocarriers can be considered a promising strategy for stimulating axonal regeneration in central and peripheral nervous systems.</P>

Sixty‐five gene‐based risk score classifier predicts overall survival in hepatocellular carcinoma

Kim, Soo Mi,Leem, Sun‐,Hee,Chu, In‐,Sun,Park, Yun‐,Yong,Kim, Sang Cheol,Kim, Sang‐,Bae,Park, Eun Sung,Lim, Jae Yun,Heo, Jeonghoon,Kim, Yoon Jun,Kim, Dae‐,Ghon,Kaseb, Ahme Wiley Subscription Services, Inc., A Wiley Company 2012 Hepatology Vol.55 No.5

<P><B>Abstract</B></P><P>Clinical application of the prognostic gene expression signature has been delayed due to the large number of genes and complexity of prediction algorithms. In the current study we aimed to develop an easy‐to‐use risk score with a limited number of genes that can robustly predict prognosis of patients with hepatocellular carcinoma (HCC). The risk score was developed using Cox coefficient values of 65 genes in the training set (n = 139) and its robustness was validated in test sets (n = 292). The risk score was a highly significant predictor of overall survival (OS) in the first test cohort (<I>P</I> = 5.6 × 10<SUP>−5</SUP>, n = 100) and the second test cohort (<I>P</I> = 5.0 × 10<SUP>−5</SUP>, n = 192). In multivariate analysis, the risk score was a significant risk factor among clinical variables examined together (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.13‐1.64; <I>P</I> = 0.001 for OS). <I>Conclusion:</I> The risk score classifier we have developed can identify two clinically distinct HCC subtypes at early and late stages of the disease in a simple and highly reproducible manner across multiple datasets. (H<SMALL>EPATOLOGY</SMALL> 2011)</P>

Hedgehog Oral Viral Papilloma

Ahmed K. Elfadl(아메드엘파드),Eun-Joo Lee(이은주),Hyeong-Mi Kim(김형미),Yong Deuk Kim(김용득),Myung-Jin Chung(정명진),Jin-Kyu Park(박진규),Tae-Hwan Kim(김태환),Shin-Yoon Kim(김신윤),Soong-Gu Ghim(김숭구),Jun Young Kim(김준영),Kyu-Shi 한국생명과학회 2017 생명과학회지 Vol.27 No.5

고슴도치에서 발생한 바이러스성 섬유 유두종의 조직학적 소견과 관련하여 증례보고를 하고자 한다. 상악에서 발생한 단발성의 종대된 종괴는 원형 혹은 타원형의 외양을 보였으며, 표면은 거칠었며, 잇몸과 동일한 색을 나타내었고, 직경은 6×3×2 mm였다. 외과적으로 절제 후, 종괴는 병리조직학적 진단을 위해 경북대학교 수의과대학 병리학교실에 의뢰되었다. 종괴는 처리과정을 거친 후 조직절편 과정 후에 조직병리학적 진단을 위해 염색 과정을 거쳤다. 조직병리학적 진단으로 본 종괴는 Fibro-papilloma로 진단되었다. 조직병리학적으로 종괴는 유두종 바이러스에 의한 사마귀와 비슷한 조직학적 소견을 보였으며, 가시층 및 기저층의 비후, 각질세포에서의 핵내봉입체, 점막하층의 섬유화가 특징적으로 관찰되었다. 또한 Macchiavello염색을 통하여 붉은 색의 핵내봉입체를 동정하였으며, 유두종의 자발적인 퇴축과 관련이 있는 림프구의 침윤은 관찰되지 않아, 본 증례의 종양의 자발적인 퇴축의 가능성이 낮음을 시사하였다. 유두종증은 주로 어린 연령의 동물에서 다발하는 것으로 알려졌으나, 본 증례의 경우 5년령의 고슴도치에서 발생한 경우로, 감소한 면역력과 관련 있는 것으로 사료된다. 본 증례는 고슴도치에서 발생한 유두종 바이러스에 의한 섬유성 유두종 증례로서, 본 저자가 알고 있는 한 최초 보고인 것으로 사료된다. Here we describe the histological lesion of a viral fibro-papilloma in a hedgehog. After surgical removal from maxilla, the solitary swollen mass was round to oval, yellowish with rough surface and measuring 6×3×2mm approximately. The tumor mass was submitted to the laboratory of pathology, college of veterinary medicine, Kyungpook National University for pathological diagnosis. Pathological examination of the tumor was established, the tumor was described grossly and sample was trimmed, sectioned and routinely prepared for histopathological evaluation. The tumor mass was diagnosed as viral fibro-papilloma, as the histological picture showed characteristic features of warts caused by papillomaviruses. The tumor characterized by thickening of the stratum spinosum (acanthosis) and basale, koilocytosis, intra-nuclear inclusion bodies in keratinocytes and fibrosis of submucosa. Further, viral inclusion bodies were demonstrated by Machiavello stain giving red color to the nuclei. No lymphocytes that responsible for regression of the wart could be detected, suggesting the poor possibility of spontaneous regression of the tumor. Papillomatosis is a disease of young animals, but in our case the infected Hedgehog was 5 years old, that maybe due to an impaired immune system, which is also shown by absence of lymphocytes. To the best knowledge of the author, this case presents the first report of viral fibropapillomatosis in Hedgehog.

ERRATUM : Outcome of Inhaler Withdrawal in Patients Receiving Triple Therapy for COPD

Kim, Sae Ahm,Lee, Ji-Hyun,Kim, Eun-Kyung,Kim, Tae-Hyung,Kim, Woo Jin,Lee, Jin Hwa,Yoon, Ho Il,Baek, Seunghee,Lee, Jae Seung,Oh, Yeon-Mok,Lee, Sang-Do The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.3