• Childhood Kidney Diseases
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• v.15 no.2
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• pp.116-124
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• 2011

Acute kidney injury (AKI) can result in mortality or progress to chronic kidney disease in hospitalized patients. Although serum creatinine has long been used as the best biomarker for diagnosis of AKI, it has some clinical limitations, especially in children. New biomarkers are needed for early diagnosis, differential diagnosis, and reliable prediction of prognosis in AKI. Up to the present, candidate AKI biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), livertype fatty acid-binding protein (L-FABP), matrix metalloproteinase-9 (MMP-9), and Nacetyl-$\ss$-D-glucosaminidase (NAG). However, whether these are superior to serum creatinine in the confirmation of diagnosis and prediction of prognosis in AKI is unclear. Further studies are needed for clinical application of these new biomarkers in AKI.

• Journal of Yeungnam Medical Science
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• v.37 no.2
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• pp.73-78
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• 2020

Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.

• Environmental Mutagens and Carcinogens
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• v.22 no.1
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• pp.54-59
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• 2002

We have used cDNA microarray hybridization to identify gene regulated in response to gamma-irradiation in U-937 cell. The cDNA-chip was composed entirely of 1,000 human cancer related gene including apoptosis and angiogenesis etc. In gamma-irradiated U-937 cell, highly charged protein, ribosomal protein L32, four and a half LIM domains 3, lipocalin 2 (oncogene 24p3) and interleukin 15, ataxia telangiectasia mutated (includes complementation groups A, C and D) genes showed increased level of its transcription, and cell division cycle 25A, dihydrofolate reductase, topoisomerase (DNA) II beta(180kD), kinase suppressor of ras and strarigin genes showed reduced level of its transcription compared to untreated U-937 cell. The significant change of level of transcription was not found in well-known ionizing radiation(IR)-responsive gene, such as transcription factor TP53 and p53 related gene, except ataxia telangiectasia mutated gene.

• Horticultural Science & Technology
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• v.30 no.6
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• pp.626-634
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• 2012

There are variations among grapevine genotypes in the levels of tolerance to cold, and cold-hardiness of grapevine has been affected by the change of short-term environment during over-wintering. In this study, the responses of vines to cold in open field and rain-shelter system were investigated to obtain useful information in increasing the tolerance to cold in grape cultivation. Total carbohydrate content of bearing mother branches was higher in the rain-shelter system than in the open field, and lower in the branches of 'Muscat Bailey A' than in 'Campbell Early' and 'Kyoho'. Bud-burst and shoot growth were better in the rain-shelter system than in open field, whereas there is no significant difference among the treatments of net beside vines. There was also low incidence of gray mold in rain shelter system. Stilbene compounds such as t-piceid, resveratrol, piceatannol, c-piceid were accumulated in the cold-treated shoot from vine cuts harvested in rain shelter system. Genes of chalcone isomerase, manganese superoxide dismutase, proline rich protein 2, and temperature induced lipocalin were highly expressed in the cold-treated shoot from vine cuts harvested in rain shelter system. While there was not change of air temperature, but high reduction of wind speed in the rain shelter system compared to open field, and increase in the reduction of wind speed by net treatment. The damage of grapevines by cold in the extreme low temperature could be reduced by keeping them in the rain shelter system with net during winter season.

• Natural Product Sciences
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• v.28 no.4
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• pp.194-200
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• 2022

Albizia julibrissin Durazz. (AJ; family Minosaceae) is widely distributed worldwide, and its stem bark has been used as a traditional herbal medicine. Acute kidney injury (AKI) is a clinical syndrome that results in sudden loss of renal function. This study aimed to investigate the effects of AJ against cisplatin-induced AKI using a human kidney proximal tubule epithelial cell line (HK-2) and cisplatin-treated mice. In vitro, cisplatin treatment increased apoptosis in HK-2 cells. However, AJ treatment decreased apoptosis of cisplatin-treated HK-2 cells. In vivo, cisplatin treatment accelerated renal injury by increasing the levels of renal injury markers, such as blood urea nitrogen, creatinine, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin, which were reversed by AJ treatment. Histopathologically, AJ treatment resulted in decreased renal damage with less tubular necrosis and brush border desquamation compared with the AKI group. Additionally, cisplatin treatment upregulated mitochondrial fission, a pathological characteristic of AKI, which was downregulated by AJ treatment. Along with increased mitochondrial fission, AJ treatment also reduced cisplatin-induced apoptosis. These results suggest that AJ may be a potential therapeutic agent for cisplatin-induced AKI.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.135-143
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• 2018

Tumor necrosis $factor-{\alpha}$ ($TNF{\alpha}$) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which $TNF{\alpha}$-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS ($10{\mu}g/ml$) in the presence or absence of a type 1 TACE inhibitor ($1{\mu}M$) or type 2 TACE inhibitor ($10{\mu}M$). LPS treatment induced increased serum creatinine, $TNF{\alpha}$, and urinary neutrophil gelatinase-associated lipocalin. Angiotensin II type 1 receptor, mitogen activated protein kinase (MAPK), and TACE increased, while angiotensin-converting enzyme-2 (ACE2) expression decreased in LPS-induced acute kidney injury and LPS-treated HK-2 cells. LPS induced reactive oxygen species and the down-regulation of ACE2, and these responses were prevented by TACE inhibitors in HK-2 cells. TACE inhibitors increased cell viability in LPS-treated HK-2 cells and attenuated oxidative stress and inflammatory cytokines. Our findings indicate that LPS activates renin angiotensin system components via the activation of TACE. Furthermore, inhibitors of TACE are potential therapeutic agents for kidney injury.

• Biomedical Science Letters
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• v.15 no.3
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• pp.261-263
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• 2009

Methylprednisolone is a synthetic glucocorticoid which is usually taken intravenously for many neurosurgical diseases which cause edema including brain tumor, and trauma including spinal cord injury. Methylprednisolone reduces swelling and decreases the body's immune response. It is also used to treat many immune and allergic disorders, such as arthritis, lupus, psoriasis, asthma, ulcerative colitis, and Crohn's disease. To identify genes expressed during methylprednisolone treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up- or down-regulated genes) which are methylprednisolone differentially expressed in neurons. Lipocalin 3 is the gene most significantly increased among 772 up-regulated genes (more than 2 fold over-expression) and Aristaless 3 is the gene most dramatically decreased among 959 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Fgb, Thbd, Cfi, F3, Kngl, Serpinel, C3, Tnfrsf4 and Il8rb are involved stress-response gene, and Nfkbia, Casp7, Pik3rl, I11b, Unc5a, Tgfb2, Kitl and Fgf15 are strongly associated with development. Cell cycle associated genes (Mcm6, Ccnb2, Plk1, Ccnd1, E2f1, Cdc2a, Tgfa, Dusp6, Id3) and cell proliferation associated genes (Ccl2, Tnfsf13, Csf2, Kit, Pim1, Nr3c1, Chrm4, Fosl1, Spp1) are down-regulated more than 2 times by methylprednisolone treatment. Among the genes described above, 4 up-regulated genes are confirmed those expression by RT-PCR. We found that methylprednisolone is related to expression of many genes associated with stress response, development, cell cycle, and cell proliferation by DNA microarray analysis. However, We think further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by methylprednisolone. The resulting data will give the one of the good clues for understanding of methylprednisolone under molecular level in the neurons.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.837-845
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• 2014

Background: Overweight and obesity are recognized as major drivers of cancers including breast cancer. Several cytokines, including interleukin-6 (IL-6), IL-10 and lipocalin 2 (LCN2), as well as dysregulated cell cycle proteins are implicated in breast carcinogenesis. The nuclear, casein kinase and cyclin-dependent kinase substrate-1 (NUCKS-1), is a nuclear DNA-binding protein that has been implicated in several human cancers, including breast cancer. Objectives: The present study was conducted to evaluate NUCKS-1 mRNA expression in breast tissue from obese patients with and without breast cancer and lean controls. NUCKS-1 expression was correlated to cytokine profiles as prognostic and monitoring tools for breast cancer, providing a molecular basis for a causal link between obesity and risk. Materials and Methods: This study included 39 females with breast cancer (G III) that was furtherly subdivided into two subgroups according to cancer grading (G IIIa and G IIIb) and 10 control obese females (G II) in addition to 10 age-matched healthy lean controls (G I). NUCKS-1 expression was studied in breast tissue biopsies by means of real-time PCR (RT-PCR). Serum cytokine profiles were determined by immunoassay. Lipid profiles and glycemic status as well as anthropometric measures were also recorded for all participants. Results: IL-6, IL-12 and LCN2 were significantly higher in control obese and breast cancer group than their relevant lean controls (p<0.05), while NUCKS-1 mRNA expression was significantly higher in the breast cancer group compared to the other groups (p<0.05). Significant higher levels of IL-6, IL-12, and LCN2 as well as NUCKS-1 mRNA levels were reported in G IIIb than G IIIa, and positively correlated with obesity markers in all obese patients. Conclusions: Evaluation of cytokine levels as well as related gene expression may provide a new tool for understanding interactions for three axes of carcinogenesis, innate immunity, inflammation and cell cycling, and hope for new strategies of management.

• Childhood Kidney Diseases
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• v.20 no.2
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• pp.63-68
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• 2016

Purpose: Disruption of normal renal development can lead to congenital anomalies of the kidney and urinary tract, including renal hypodysplasia. We aimed to clarify whether small kidney size affects clinical manifestations in children with urinary tract infection (UTI). Methods: One hundred fifty-four patients who had their first symptomatic UTI between January 2014 and June 2015 were enrolled in this study. Differences in kidney size were estimated based on percent uptake of $^{99m}Tc-$ dimercaptosuccinic acid (DMSA) in scintigraphy. The patients who showed more than 10% difference in kidney size on DMSA scintigraphy with none or minimal cortical defects were included in group A. (group A, n=17). Laboratory, clinical, and imaging results were compared with those of the other patients (group B, n=137). Results: Group A had a relatively higher incidence of vesicoureteral reflux than group B (44% vs 20%, P<0.05). The levels of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum C-reactive protein were significantly higher in group A (193 [64-337] vs 91 [59-211] ng/mL and 4.1 [0.5-11.9] vs 2.1 [0.7-5.3] ng/mL, respectively; all P <0.05). Linear regression analysis revealed that plasma NGAL level strongly correlated with the difference in renal uptake in DMSA scintigraphy in group A ($R^2=0.505$). Conclusion: The difference in kidney size could influence the clinical course and severity of pediatric UTI.

• Toxicological Research
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• v.28 no.3
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• pp.179-185
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• 2012

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (${\beta}2m$), glutathione S-transferase alpha (GST-${\alpha}$), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.