1.Sphingomonas Paucimobilis-derived Extracellular Vesicles Reverse Aβ-induced Dysregulation of Neurotrophic Factors, Mitochondrial Function, and Inflammatory Factors through MeCP2-mediated Mechanism
Eun-Hwa LEE ; Hyejin KWON ; So-Young PARK ; Jin-Young PARK ; Jin-Hwan HONG ; Jae-Won PAENG ; Yoon-Keun KIM ; Pyung-Lim HAN
Experimental Neurobiology 2025;34(1):20-33
Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.
2.Sphingomonas Paucimobilis-derived Extracellular Vesicles Reverse Aβ-induced Dysregulation of Neurotrophic Factors, Mitochondrial Function, and Inflammatory Factors through MeCP2-mediated Mechanism
Eun-Hwa LEE ; Hyejin KWON ; So-Young PARK ; Jin-Young PARK ; Jin-Hwan HONG ; Jae-Won PAENG ; Yoon-Keun KIM ; Pyung-Lim HAN
Experimental Neurobiology 2025;34(1):20-33
Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.
3.Sphingomonas Paucimobilis-derived Extracellular Vesicles Reverse Aβ-induced Dysregulation of Neurotrophic Factors, Mitochondrial Function, and Inflammatory Factors through MeCP2-mediated Mechanism
Eun-Hwa LEE ; Hyejin KWON ; So-Young PARK ; Jin-Young PARK ; Jin-Hwan HONG ; Jae-Won PAENG ; Yoon-Keun KIM ; Pyung-Lim HAN
Experimental Neurobiology 2025;34(1):20-33
Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.
4.Sphingomonas Paucimobilis-derived Extracellular Vesicles Reverse Aβ-induced Dysregulation of Neurotrophic Factors, Mitochondrial Function, and Inflammatory Factors through MeCP2-mediated Mechanism
Eun-Hwa LEE ; Hyejin KWON ; So-Young PARK ; Jin-Young PARK ; Jin-Hwan HONG ; Jae-Won PAENG ; Yoon-Keun KIM ; Pyung-Lim HAN
Experimental Neurobiology 2025;34(1):20-33
Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.
5.Inhibition of HIF1α and PDK Induces Cell Death of Glioblastoma Multiforme.
Jiwon Esther HAN ; Pyung Won LIM ; Chul Min NA ; You Sik CHOI ; Joo Young LEE ; Yona KIM ; Hyung Woo PARK ; Hyo Eun MOON ; Man Seung HEO ; Hye Ran PARK ; Dong Gyu KIM ; Sun Ha PAEK
Experimental Neurobiology 2017;26(5):295-306
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.
Anoxia
;
Brain Neoplasms
;
Cell Death*
;
Cell Line
;
Dichloroacetic Acid
;
Glioblastoma*
;
Glucose
;
Glycolysis
;
Metabolism
;
Oxidative Phosphorylation
;
Oxidoreductases
;
Phosphotransferases
;
Pyruvic Acid
6.Prevalence of Significant Coronary Arterial Disease in Adult Patients who Underwent Valvular Surgery in Korea.
Uhng Lim CHOI ; Sun Hwa LEE ; Jae Hyeong PARK ; Seok Woo SEONG ; Jun Hyung KIM ; Jae Hwan LEE ; Si Wan CHOI ; Jin Ok JEONG ; In Whan SEONG ; Kyoung Suk RHEE ; Jei Keon CHAE ; Won Ho KIM ; Jae Ki KO ; Myung Hoon NA ; Seung Pyung LIM ; Kyung Hwa KIM ; Jong Bum CHOI
Korean Journal of Medicine 2012;83(1):75-82
BACKGROUND/AIMS: The identification of significant coronary arterial disease (CAD) is important to reduce perioperative ischemic insult and the possibility of repeated open-chest surgery in patients scheduled to undergo valvular surgery. However, there are no published data on the incidence of significant CAD in these patients. Thus, we examined the prevalence of significant CAD in patients scheduled to undergo valvular surgery. METHODS: From January 2005 to June 2011, all consecutive adult patients diagnosed with significant valvular disease and scheduled for an elective open valvular operation were retrospectively investigated at Chungnam National University Hospital and Chonbuk National University Hospital. Patients who underwent emergent valvular operations due to acute aortic dissection or trauma and concomitant valvular operations at the time of coronary artery bypass graft (CABG) surgery were excluded. RESULTS: During the study period, a total of 431 patients (58 +/- 13 years old, 204 males) were included. The distributions of mitral (241 patients) and aortic valvular disease (230 patients) were similar. Coronary angiography was performed in 297 patients (68.9%). Of these, 36 (12.1%) showed significant CAD and 32 underwent concomitant CABG operations. Based on a multivariate analysis, the presence of CAD was significantly associated with old age (> or = 65 years old) [odds ratio (OR) = 3.081, 95% confidence interval (CI) = 1.372-6.921, p = 0.006], more cardiovascular risk factors (> or = 3) (OR = 3.002, 95% CI = 1.386-6.503, p = 0.005), and the presence of aortic stenosis (OR = 2.763, 95% CI = 1.269-6.013, p = 0.010). CONCLUSIONS: The incidence of significant CAD was 12.1% in adult patients who underwent valvular operations in Korea. CAD was more common in patients with old age, aortic stenosis, and multiple cardiovascular risk factors.
Adult
;
Aortic Valve Stenosis
;
Coronary Angiography
;
Coronary Artery Bypass
;
Coronary Artery Disease
;
Heart Valve Diseases
;
Humans
;
Incidence
;
Korea
;
Multivariate Analysis
;
Prevalence
;
Retrospective Studies
;
Risk Factors
;
Transplants
7.Antidepressant-like Effect of Kaempferol and Quercitirin, Isolated from Opuntia ficus-indica var. saboten.
Soo Hyun PARK ; Yun Beom SIM ; Pyung Lim HAN ; Jin Koo LEE ; Hong Won SUH
Experimental Neurobiology 2010;19(1):30-38
Opuntia ficus-indica var. saboten. is widely cultivated in Jeju Island (South Korea) for use in manufacture of health foods. This study described antidepressant effect of two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. The expression of the hypothalamic POMC mRNA or plasma beta-endorphin levels were increased by extract of Opintia ficus-indica var. saboten or its flavoniods administered orally. In addition, antidepressant activity was studied using tail suspension test (TST), forced swimming test (FST) and rota-rod test in chronically restraint immobilization stress group in mice. After restraint stress (2 hrs/day for 14 days), animals were kept in cage for 14 days without any further stress, bet with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with kaempferol or quercitrin (30 mg/kg/day). POMC mRNA or plasma beta-endorphin level was increased by extract of Opintia ficus-indica var. saboten and its flavoniods. In addition, immobility time in TST and FST was significantly reduced by kaempferol or quercitrin. In rota-rod test, the time of permanence was maintained to the semblance of control group in turning at 15 rpm. Our results suggest that two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. show a potent antidepressant effect.
Animals
;
beta-Endorphin
;
Diet
;
Flavonoids
;
Hindlimb Suspension
;
Immobilization
;
Kaempferols
;
Mice
;
Opuntia
;
Plasma
;
Pro-Opiomelanocortin
;
Quercetin
;
RNA, Messenger
;
Swimming
;
Food, Organic
8.Surgical Treatment for Idiopathic Granulomatous Mastitis.
Soon Young TAE ; Seung Won LEE ; Sun Uk HAN ; Hee Doo WOO ; Doo Min SON ; Sung Yong KIM ; Hyung Chul KIM ; Min Hyuk LEE ; Ok Pyung SONG ; Cheol Wan LIM
Journal of the Korean Surgical Society 2009;77(3):153-160
PURPOSE: Idiopathic granulomatous mastitis is a rare benign inflammatory breast disease of an unknown etiology and the optimal treatment remains controversial. The aim of this study is to evaluate the efficacy of surgically complete excision in patients with idiopathic granulomatous mastitis. METHODS: Between March 2005 and November 2008, we treated 14 cases that were diagnosed with idiopathic granulomatous mastitis. Prospectively, we treated the cases with complete surgical excision with or without steroid therapy in all patients. RESULTS: The mean age of the patients was 36 years (range 30 to 53 years). All cases performed were complete excision with or without steroid therapy. The median follow up period was 26 months (range 5 to 50 months) and all cases had no recurrence. 13 patients out of the 14 were satisfied with the cosmesis of the treated breast. CONCLUSION: We conclude that the treatment of choice for idiopathic granulomatous mastitis is surgically complete excision.
Breast
;
Breast Diseases
;
Follow-Up Studies
;
Granulomatous Mastitis
;
Humans
;
Prospective Studies
;
Recurrence
9.A Case of Colon Cancer Associated with Colonic Tuberculosis.
Sang Chul YUN ; Eung Jin SHIN ; Ok Pyung SONG ; Hyung Chul KIM ; Cheol Wan LIM ; Gyu Seok CHO ; Chong Woo CHU ; Hyo Won LEE
Journal of the Korean Society of Coloproctology 2007;23(3):194-198
Inflammatory bowel disease, such as ulcerative colitis and Crohn's disease, has a potential risk of developing into colorectal cancer. However, there is little relationship between intestinal tuberculosis and colon cancer because intestinal tuberculosis is a curable disease and has a relatively short disease course. Nevertheless, there have been a few case reports of intestinal tuberculosis associated with colon cancer. There was a case report in which the carcinoma facilitated entry of tubercle bacilli with development of a secondary infection, and ulcerative lesions of tuberculosis may be precursors of carcinomas. We experienced a 77-year-old woman who had intestinal tuberculosis combined with ascending colon cancer. She visited our hospital because of abdominal pain and constipation. Colonoscopy showed a luminal obstruction mass in the ascending colon. Histologic examination revealed an adenocarcinoma. After surgery, the surgical specimen disclosed an adenocarcinoma in the cecum and ascending colon and intestinal tuberculosis around the cancer site of the cecum. Herein, we report a rare case of colon cancer co-existing with colonic tuberculosis with a review of the literature.
Female
;
Humans
;
Adenocarcinoma
10.A Prospective Study Comparing of Laparoscopy-assisted vs Conventional Open Gastrectomy for Gastric Cancer.
Gyu Seok CHO ; Hyung Chul KIM ; Moon Su LEE ; Cheol Wan LIM ; Eung Jin SHIN ; Chong Woo CHU ; Kil Ho KANG ; Young Jin KIM ; Ki Won YU ; Hyo Won LEE ; Ok Pyung SONG
Journal of the Korean Surgical Society 2006;70(3):175-181
PURPOSE: The technique of laparoscopic gastrectomy has developed for early gastric cancer, but a few reports have studied the objective advantages of laparoscopic techniques in a prospective manner. The purpose of this study is to compare laparoscopy-assisted gastrectomy (LG) with conventional open gastrectomy (OG) by the operative outcomes, the recovery of bowel function, and the complications in a prospective nonrandomized manner. METHODS: We studied 73 patients with gastric cancer who were diagnosed as stage I (IA, IB) preoperatively between July 2003 and September 2004. 38 patients underwent LG and 35 patients underwent OG. All patients underwent radical lymphadenectomy (D2), and were treated by a single surgeon. RESULTS: Patients of the two groups were comparable by age, sex, BMI (Body mass index), preoperative stages and mean number of retrived lymph nodes. The mean operative time was shorter in the OG group (P=0.012), and the mean amount of blood loss was significantly less in the LG group than in the OG group (P=0.002). The patients in the LG group recovered bowel function significantly earlier than those in the OG group (P=0.01), thus, the mean hospital stay was significantly shorter in the LG group (P=0.007). The postoperative pain was significantly lower in the LG group (P<0.001). The postoperative complications were 4 cases in the LG group and 6 cases in the OG group, and there were no conversions and no mortalities. CONCLUSION: LG, when compared with OG, has several advantages, including less blood loss, rapid return of gastrointestinal function, less pain, and shorter hospital stay with compromising the cure rate. In addition, for evaluation of the validity of laparoscopic surgery in gastric cancer, a large scaled randomized prospective multicenter study is required.
Gastrectomy*
;
Humans
;
Laparoscopy
;
Length of Stay
;
Lymph Node Excision
;
Lymph Nodes
;
Mortality
;
Operative Time
;
Pain, Postoperative
;
Postoperative Complications
;
Prospective Studies*
;
Stomach Neoplasms*

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