• Childhood Kidney Diseases
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• v.17 no.2
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• pp.86-91
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• 2013

Purpose: The aim of this study was to verify renal inflammation following Kawasaki disease (KD) using single photon emission computed tomography along with Technetium-99m dimercaptosuccinic acid scintigraphy (DMSA renal SPECT). Methods: From March 2011 to October 2011, 15 patients diagnosed with KD at the National Health Insurance System Ilsan Hospital were enrolled in the study. All patients underwent DMSA renal SPECT to evaluate renal involvement during the acute phase of KD. Urine ${\beta}2$-microglobulin (${\beta}2$-MG), a marker of renal proximal tubular dysfunction, was also measured to assess renal damage. Results: All 15 patients had normal renal function test results. However, microscopic hematuria and pyuria were observed in 13% and 33% of the patients, respectively. Moreover, urine ${\beta}2$-MG was elevated in 46% of the patients. In addition, patients were divided into two groups based on ${\beta}2$-MG level: those with an increased ${\beta}2$-MG level, and those with a normal ${\beta}2$-MG level. No significant differences were found between these two groups in clinical characteristics, laboratory, sonography, and echocardiography findings. All patients' DMSA renal SPECT scans were normal. Conclusion: Our study showed that mild abnormalities in the urinalysis and elevated urine ${\beta}2$-MG were the only findings of renal involvement in KD. However, no aggressive renal manifestations were detected on DMSA renal SPECT.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.305-315
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• 2021

Background: Panax stipuleanatus represents a folk medicine for treatment of inflammation. However, lack of experimental data does not confirm its function. This article aims to investigate the analgesic and anti-inflammatory activities of triterpenoid saponins isolated from P. stipuleanatus. Methods: The chemical characterization of P. stipuleanatus allowed the identification and quantitation of two major compounds. Analgesic effects of triterpenoid saponins were evaluated in two models of thermal- and chemical-stimulated acute pain. Anti-inflammatory effects of triterpenoid saponins were also evaluated using four models of acetic acid-induced vascular permeability, xylene-induced ear edema, carrageenan-induced paw edema, and cotton pellet-induced granuloma in mice. Results: Two triterpenoid saponins of stipuleanosides R₁ (SP-R₁) and R₂ (SP-R₂) were isolated and identified from P. stipuleanatus. The results showed that SP-R₁ and SP-R₂ significantly increased the latency time to thermal pain in the hot plate test and reduced the writhing response in the acetic acid-induced writhing test. SP-R₁ and SP-R₂ caused a significant decrease in vascular permeability, ear edema, paw edema, and granuloma formation in inflammatory models. Further studies showed that the levels of inflammatory mediators, nitric oxide, malondialdehyde, tumor necrosis factor-α, and interleukin 6 in paw tissues were downregulated by SP-R₁ and SP-R₂. In addition, the rational harvest of three- to five-year-old P. stipuleanatus was preferable to obtain a higher level of triterpenoid saponins. SP-R₂ showed the highest content in P. stipuleanatus, which had potential as a chemical marker for quality control of P. stipuleanatus. Conclusion: This study provides important basic information about utilization of P. stipuleanatus resources for production of active triterpenoid saponins.

• Journal of Life Science
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• v.31 no.5
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• pp.464-474
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• 2021

Inflammation induced by metabolic syndromes, cancers, injuries, and sepsis can alter cellular metabolism by reducing mitochondrial function via oxidative stress, thereby resulting in neuropathy and muscle atrophy. In this study, we investigated whether butyrate, a short chain fatty acid produced by gut microbiota, could prevent mitochondrial dysfunction and muscle atrophy induced by lipopolysaccharide (LPS) in the C2C12 cell line. LPS-activated MAPK signaling pathways increased the levels of the mitochondrial fission signal, p-DRP1 (Ser616), and the muscle atrophy marker, atrogin 1. Interestingly, butyrate significantly inhibited the phosphorylation of JNK and p38 and reduced the atrogin 1 level in LPS-treated C2C12 cells while increasing the phosphorylation of DRP1 (Ser637) and levels of mitofusin2, which are both mitochondrial fusion markers. Next, we investigated the effect of MAPK inhibitors, finding that butyrate had the same effect as JNK inhibition in C2C12 cells. Also, butyrate inhibited the LPS-induced expression of pyruvate dehydrogenase kinase 4 (PDK4), resulting in decreased PDHE1α phosphorylation and lactate production, suggesting that butyrate shifted glucose metabolism from aerobic glycolysis to oxidative phosphorylation. Finally, we found that these effects of butyrate on LPS-induced mitochondrial dysfunction were caused by its antioxidant effects. Thus, our findings demonstrate that butyrate prevents LPS-induced muscle atrophy by improving mitochondrial dynamics and metabolic stress via the inhibition of JNK phosphorylation. Consequently, butyrate could be used to improve LPS-induced mitochondrial dysfunction and myopathy in sepsis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.1
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• pp.52-60
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• 2022

Purpose: Colonoscopy is considered the most reliable method for the diagnosis of juvenile polyps. However, colonoscopic screening is an invasive and expensive procedure. Fecal calprotectin (FCP), a marker of intestinal inflammation, has been shown to be elevated in patients with polyps. Therefore, this study aimed to evaluate FCP as a screening biomarker for the diagnosis of juvenile polyps. Methods: This cross-sectional, observational study was conducted at the Pediatric Gastroenterology and Nutrition Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. For children with polyps, colonoscopic polypectomy and histopathology were performed. FCP levels were analyzed before and 4 weeks after polypectomy in all patients. Information was recorded in a datasheet and analyzed using the computer-based program SPSS. Results: The age of the children was between 2.5 and 12 years. Approximately 93% of the polyps were found in the rectosigmoid region. Children with juvenile polyps had elevated levels of FCP before polypectomy that subsequently normalized after polypectomy. The mean FCP levels before and after polypectomy were 277±247 ㎍/g (range, 80-1,000 ㎍/g) and 48.57±38.23 ㎍/g (range, 29-140 ㎍/g) (p<0.001), respectively. The FCP levels were significantly higher in patients with multiple polyps than in those with single polyps. Moreover, mean FCP levels in patients with single and multiple polyps were 207.6±172.4 ㎍/g and 515.4±320.5 ㎍/g (p<0.001), respectively. Conclusion: Colonic juvenile polyps were found to be associated with elevated levels of FCP that normalized after polypectomy. Therefore, FCP may be recommended as a noninvasive screening biomarker for diagnosis of colonic juvenile polyps.

• Journal of Nutrition and Health
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• v.55 no.3
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• pp.348-358
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• 2022

Purpose: Hyperglycemia accelerates the formation of advanced glycation end products (AGEs), a group of compounds formed via non-enzymatic glycation/glycoxidation. Type 2 diabetes mellitus (T2DM) is related to oxidative stress, resulting in some overgeneration of AGEs. The accumulation of AGEs in T2DM patients leads to increased inflammation, DNA damage, tissue damage, progression of diabetic microvascular disease, and nephropathy. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme. Expression of HO-1 in the endothelium and in muscle monocytes/macrophages was upregulated upon exposure to reactive oxygen species or oxidized low-density lipoprotein. Cells activated by oxidative stress are reported to release HO-1 in the serum. In the current study, we discuss the oxidative status according to the level of AGEs and the association of HO-1 with AGEs or urinary DNA damage marker in type 2 diabetic Korean patients. Methods: This study enrolled 36 diabetic patients. Subjects were classified into two groups by serum AGEs level (Low AGEs group: < 0.85 ng/mL serum AGEs; High AGEs group: ≥ 0.85 ng/mL serum AGEs). Body composition was measured using bioelectrical impedance analysis. Blood and urinary parameters were measured using commercial kits. Results: No significant differences were observed in the general characteristics and body composition between the two groups. Serum HO-1 concentration was significantly higher in the High AGEs group than in the Low AGEs group. After adjustment of age and gender, a correlation was performed to assess the association between serum HO-1 and serum AGEs or urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Our results indicate that serum HO-1 is positively correlated with serum AGEs and urinary 8-OHdG. Conclusion: Taken together, our results indicate that in diabetes patients, a high level of HO-1 is associated with a high concentration of AGEs and 8-OHdG, probably reflecting a protective response against oxidative stress.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.665-679
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• 2022

Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

• Molecules and Cells
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• v.45 no.3
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• pp.134-147
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• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

• The Korea Journal of Herbology
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• v.39 no.3
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• pp.57-67
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• 2024

Objectives : The aim of this study is to evaluate the potential biological activity of Veronica incana extracts (VIE) through in vitro, ex vivo, and in vivo experiments. Methods : In vitro, we conducted analyses on the total polyphenol (TP) and total flavonoid (TF) levels, alongside DPPHand ABTS radical scavenging activities. Ex vivo evaluations on adipose tissue measured glycerol release as a marker of lipolysis. In LPS-induced RAW 264.7 cells, we quantified nitric oxide (NO) production. Following H₂O₂ induction in U2OS cells, we performed mitochondrial assays such as MitoSox and MitoTracker. Moreover, Bodipy assays were conducted in 3T3-L1 cells. In vivo, we performed anti-osteoarthritis effect of VIE against monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Results : The results presented encompass a myriad of models, from cell culture to animal experiments as well as ex vivo studies. VIE demonstrated high TP and TF contents, potent DPPH and ABTS scavenging activities, and regulated glycerol release. Moreover, the inhibition of NO production in LPS-induced inflammation was notably confirmed and the reduction of lipid droplets was distinctly shown. Furthermore, in H₂O₂-induced U2OS cells, MitoSox was effectively reduced while MitoTracker noticeably increased. In vivo assays confirmed a significant increase in hindpaw weight distribution (HWD) decreased by MIA after VIE treatment. Additionally, VIE inhibited serum inflammatory cytokines (TNF-𝛼, IL-6, and IL-1𝛽) and MDA levels in joint tissue. Conclusion : In conclusion, Veronica incana exhibited various pharmacological effects including antioxidant, anti-obesity, and anti-inflammatory properties.

• Journal of Oral Medicine and Pain
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• v.30 no.3
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• pp.287-300
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• 2005

Squamous cell carcinoma (SCC) in head and neck show a variability in the response to chemotherapy, even when it present with similar histological tumor type, grade, and clinical stage. The purpose of present study it to identify predictive bio-marker for the sensitivity or resistance to conventional chemotherapeutic agents, 5-fluorouracil (5-FU) and Cisplatin Oral cancer cell lines were used in present study. MTT assay was performed to evaluate the sensitivity and/or resistance to 5-FU and Cisplatin. And RT-PCR was carried out for evaluation of the mRNA expressions of various genes associated with mutation, inflammation (COX pathway), cell cycle, senescence and extracellular matrix (ECM). The molecules which are correlated with the sensitivity to 5-FU are XPA, XPC, OGG, APEX, COX-2, PPAR, Cyclin E, Cyclin B1, CDC2, hTERT, hTR, TIMP-3, TIMP-4 and HSP47. And the molecules are correlated with the sensitivity to Cisplatin are COX-1, iNOS, eNOS, PCNA, collagen 1 and MMP-9. Taken together, when choosing the appropriate chemotherpeutic agents for patients, considering the molecules which are correlated or reversely correlated is helpful to choose the resonable agents for cancer patients.

• Journal of Life Science
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• v.24 no.5
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• pp.567-572
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• 2014

Extracts of Platycodon grandiflorum have been reported to show anti-inflammatory, antioxidant, anti-metastatic, and hepato-protective effects. This study was designed to evaluate T-cell activation and M1/M2 differential macrophage activation by extracts of P. grandiflorum or P. grandiflorum containing various medicinal herbs. Using real-time RT-PCR, we analyzed expression levels of c-fos, and CD40L (T-cell activation markers) in splenocytes and iNOS, Ym1, and ARG1 in RAW 246.7 cells after treatment of CC (hot water extract of P. grandiflorum), MAEK (hot water extract of P. grandiflorum [82%] and six different plants), and HWAL (hot water extract of P. grandiflorum [7%] and eight different plants. The results showed that MAEK significantly elevated the expression of T-cell activation markers of splenocytes, with the c-fos gene activated more than 10-fold and the CD40L gene activated more than 6-fold. Although CD40L was significantly increased by CC and HWAL, the increase was only about 2-fold. In addition, CC and HWAL did not significantly activate the expression of the c-fos gene. On the other hand, CC elevated the M1 activation marker iNOS, and HWAL elevated the M2 activation marker Ym1 and ARG1 gene expression. In conclusion, MAEK could be used as an immune stimulant because of its ability to activate T cells (elicited c-fos and CD40L gene expression), whereas HWAL could serve as an anti-inflammatory agent because of its differential activation of M2 macrophages.