• Childhood Kidney Diseases
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• 제12권1호
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• pp.11-22
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• 2008

Telomeres consist of tandem guanine-thymine(G-T) repeats in most eukaryotic chromosomes. Human telomeres are predominantly linear, double stranded DNA as they ended in 30-200 nucleotides(bases,b) 3'-overhangs. In DNA replication, removal of the terminal RNA primer from the lagging strand results in a 3'-overhang of uncopied DNA. This is because of bidirectional DNA replication and specificity of unidirectional DNA polymerase. After the replication, parental and daughter DNA strands have unequal lengths due to a combination of the end-replication problem and end-processing events. The gradual chromosome shortening is observed in most somatic cells and eventually leads to cellular senescence. Telomere shortening could be a molecular clock that signals the replicative senescence. The shortening of telomeric ends of human chromosomes, leading to sudden growth arrest, triggers DNA instability as biological switches. In addition, telomere dysfunction may cause chronic allograft nephropathy or kidney cancers. The renal cell carcinoma(RCC) in women may be less aggressive and have less genomic instability than in man. Younger patients with telomere dysfunction are at a higher risk for RCC than older patients. Thus, telomeres maintain the integrity of the genome and are involved in cellular aging and cancer. By studying the telomeric DNA, we may characterize the genetic determinants in diseases and discover the tools in molecular medicine.

• IMMUNE NETWORK
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• 제20권1호
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• pp.9.1-9.21
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• 2020

Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.

• Food Science and Biotechnology
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• 제16권5호
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• pp.807-811
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• 2007

Diabetes is marked by high glucose levels and is associated with decreased bone mass and increased fracture rates. To determine if [6]-gingerol could influence osteoblast dysfunction induced by 2-deoxy-D-ribose (dRib), osteoblastic MC3T3-E1 cells was treated with dRib and [6]-gingerol and markers of osteoblast function and oxidized protein were examined. [6]-Gingerol ($10^{-7}\;M$) significantly increased the growth of MC3T3-E1 cells in the presence of 30 mM dRib (p<0.05). [6]-Gingerol ($10^{-7}\;M$) caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content, and osteocalcin secretion in the cells. We then examined the effect of [6]-gingerol on the production of osteoprotegerin and protein carbonyl in osteoblasts. Treatment with [6]-gingerol ($10^{-9}$ and $10^{-7}\;M$) increased osteoprotegerin secretion in osteoblastic cells. Moreover, [6]-gingerol ($10^{-9}$ and $10^{-7}\;M$) decreased protein carbonyl contents of osteoblastic MC3T3-E1 cells in the presence of 30 mM dRib. Taken together, these results demonstrate that [6]-gingerol inhibits dRib-induced damage and may be useful in the treatment of diabetes related bone diseases.

• Genomics & Informatics
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• 제8권2호
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• pp.76-80
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• 2010

Although autism spectrum disorder (ASD) has been thought to have a substantial genetic background, major contributing genes have yet to be identified or successfully replicated. Immunological dysfunction has been suggested to be associated with ASD, and T cell-mediated immunity was considered important for the development of ASD. In this study, we analyzed 163 ASD subjects and 97 normal controls by genomic quantitative PCR to evaluate the association between the copy number variation of the 7q34 locus, harboring the TCRB gene, and ASDs. As a result, there was no significant difference of the frequency distribution of TCRB copy numbers between ASD cases and normal controls. TCRB gene copy numbers ranged from 0 to 5 copies, and the frequency distribution of each copy number was similar between the two groups. The proportion of the individuals with <2 copies of TCRB was 52.8% (86/163) in ASD cases and 57.1% (52/91) in the control group (p=0.44). The proportion of individuals with >2 copies of TCRB was 11.7% (19/163) in ASD cases and 12.1% (11/91) in the control group (p=0.68). After the effects of sex were adjusted by logistic regression, ORs for individuals with <2 copies or >2 copies showed no significant difference compared with the diploid copy number as reference (n=2). Although we could not see the positive association, our results will be valuable information for mining ASD-associated genes and for exploring the role of T cell immunity further in the pathogenesis of ASD.

• 운동영양학회지
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• 제16권2호
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• pp.73-84
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• 2012

Thyroid hormones are important for the development of the brain including the cerebellum. In the present study, we investigated the effect of treadmill exercise on the survival of Purkinje neurons and the activation of astrocytes in the cerebellar vermis of hypothyroidism-induced rat pups. On the day of perinatal 14, pregnant rats were divided into two groups (n = 5 in each group): the pregnant control group and the pregnantmethimazole (MMI)-treated group. For the induction of hypothyroidism in the rat pups, MMI was added to the drinking water (0.02% wt/vol), from the day of perinatal 14 to postnatal 49. After delivery, male rat pups born from the pregnant control group were assigned to the control group. Male rat pups born from the MMI-treated group were divided into the hypothyroidism-induction group, the hypothyroidism-induction with treadmill exercise group, and the hypothyroidism-induction with thyroxine (T4) treatment group (n = 10 in each group). The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 4 weeks, starting on postnatal day 22. In the hypothyroidism-induced rat pups, motor coordination was reduced and Purkinje cell death and reactive astrocytes in the cerebellar vermis were increased. Treadmill exercise enhanced motor coordination, increased the survival of Purkinje neurons, down-regulated reactive astrocytes, and enhanced brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) expressions in the hypothyroidism-induced rat pups. These results suggest that treadmill exercise has beneficial effects in terms of protecting against thyroid dysfunction by increasing T3 and T4 and the related protein, BDNF, as well as TrkB, inhibition on astrocyte activation and the reduction of Purkinje cell loss regarding the cerebellum in hypothyroidism rat pups.

• 한국자원식물학회지
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• 제25권2호
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• pp.184-192
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• 2012

본 연구는 췌장베타세포인 HIT-T15 세포를 이용하여 매실주정추출물(PME)의 alloxan에 의한 산화스트레스로부터의 세포보호, 인슐린 분비능 및 항산화 효소 활성을 평가하였다. PME는 alloxan에 의해 유발된 산화스트레스로부터 세포를 보호하여 세포생존율을 증가시켰다. PME는 세포막 손상지표인 LDH 방출을 억제하였고 $NAD^+$/NADH ratio를 유의적으로 증가시켜 세포사멸이 억제되어짐을 확인하였다. 또한 alloxan 단독처리군에 비해 250 ${\mu}g$/ml PME 처리군에서 인슐린 분비량이 유의성 있게 증가하였다. Alloxan과 PME를 동시에 처리하여 HIT-T15세포의 항산화효소 활성을 측정했을 때 산화스트레스에 의해 감소되었던 항산화효소 활성이 PME에 의해 보호되는 효과를 확인하였다. 이상의 연구결과로부터 PME는 세포괴사 및 DNA fragmentation을 억제하고 세포내 항산화효소 활성을 증가시켜 alloxan에 의해 유발된 산화스트레스로부터 췌장베타세포를 보호하고 이에 따른 인슐린 분비능 조절 효과가 있는 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.261-268
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• 2016

$Foxp3^+$ $CD25^+CD4^+$ regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the effect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer effects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the effect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.

• 한국식품영양학회지
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• 제25권1호
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• pp.123-131
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• 2012

The objective of the present study was to evaluate the potential antidiabetic and antioxidant effect of the ethanol extract from Chrysanthemum cornarium L. var. spatiosum(CSE) against alloxan-induced oxidative stress in pancreatic ${\beta}$-cells, HIT-T15. In this study, the antidiabetic effect of CSE was examined using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliu bromide(MTT) cell proliferation assay, lactate dehydrogenase(LDH) release assay, $NAD^+$/NADH ratio and insulin secretion. To further investigate whether CSE is involved in the antioxidant activity of alloxan-damaged HIT-T15 cells, its antioxidant effect against alloxan-induced oxidative stress was measured in HIT-T15 cells by determining the levels of antioxidant enzymes including superoxide dismutase(SOD), glutathione S-transferase(GST), glutathione reductase(GR) and glutathione peroxidase(GPx). The results of this analysis showed that alloxan significantly decreased cell viability, increased LDH leakage, and lowered $NAD^+$/NADH ratio and insulin secretion in HIT-T15 cells. However, CSE significantly increased the viability of alloxan-treated cells and lowered LDH leakage. The intracellular NAD+/NADH ratio and insulin secretion were also significantly increased by 1.7-fold and 1.3-fold, respectively, after treatment with 100 ${\mu}g/m{\ell}$ CSE. The HIT-T15 cells treated with alloxan showed significant decreases in the activities of antioxidant enzymes, while CSE significantly elevated the levels of antioxidant enzymes. These findings suggest that CSE could have a protective effect against cytotoxicity and dysfunction of pancreatic cells in the presence of alloxan-induced oxidative stress.

• Clinical and Experimental Pediatrics
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• 제49권11호
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• pp.1211-1215
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• 2006

목 적 : 본 연구는 소아 동종 조혈모세포이식 후에 갑상선 기능의 단기간 변화와 갑상선기능이상의 빈도와 위험인자를 분석하고자 하였다. 방 법 : 2004년 1월부터 2006년 2월까지 가톨릭대학교 성모병원 소아과, 조혈모세포이식센터에서 동종 조혈모세포이식을 시행한 80명의 환자를 대상으로 연구를 하였다. 조혈모세포이식 전과 이식 후 1개월, 6개월, 12개월에 환자들의 혈청에서 TSH, T4, T3를 측정하였다. 결 과 : 조혈모세포이식을 하고 1개월 후의 갑상선 기능은 통계적으로 유의한 감소를 보이고 있었다(P<0.001). 1개월 후 갑상선 기능이상의 빈도는 80명중 43명(54%)에서 보였으며 이들 중 31명(39%)은 ETS를 보이고 있었다. 이식 후 일년 이내 갑상선 기능은 대부분 정상으로 회복되었다. 단변량 분석에 의하면 악성 질환인 경우(P=0.04)와 2도 이상의 급성 이식편대 숙주병(P=0.01)이 ETS의 위험인자였으나(P=0.04), 다변량 분석에 의하면 ETS 발생에 독립적인 위험인자는 찾을 수 없었다(P=0.19, 0.06). 결 론 : 조혈모세포이식 후 갑상선 기능이상은 초기에 높은 빈도로 발생함을 알 수 있었다. 따라서 이식 후에는 갑상선 기능의 지속적인 추적검사가 필요하다.

• Molecules and Cells
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• 제39권8호
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• pp.603-610
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• 2016

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.