• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.628-642
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• 2018

Background/Aims A Subset of patients with irritable bowel syndrome (IBS) may have mild inflammation due to immune activation. Toll-like receptors (TLRs) and cytokines may cause intestinal inflammation. We studied their expression in relation to gut microbiota. Methods Expression of TLRs and cytokines was assessed in 47 IBS patients (Rome III) and 25 controls using quantitative real-time polymerase chain reaction. Immunohistochemistry was further performed to confirm the expression of TLR-4 and TLR-5. Results Of 47 patients with IBS, 20 had constipation (IBS-C), 20 diarrhea (IBS-D), and 7 unclassified (IBS-U). The mRNA levels of TLR-4 and TLR-5 were up-regulated in IBS patients than controls (P = 0.013 and P < 0.001, respectively). Expression of TLR-4 and TLR-5 at protein level was 4.2-folds and 6.6-folds higher in IBS-D than controls. The mRNA levels of IL-6 (P = 0.003), C-X-C motif chemokine ligand 11 (CXCL-11) (P < 0.001) and C-X-C motif chemokine receptor 3 (CXCR-3) (P < 0.001) were higher among IBS patients than controls. Expression of IL-6 (P = 0.002), CXCL-11 (P < 0.001), and CXCR-3 (P < 0.001) were up-regulated and IL-10 (P = 0.012) was down-regulated in IBS-D patients than controls. Positive correlation was seen between TLR-4 and IL-6 (P = 0.043), CXCR-3, and CXCL-11 (P = 0.047), and IL-6 and CXCR-3 (P = 0.003). Stool frequency per week showed positive correlation with mRNA levels of TLR-4 (P = 0.016) and CXCR-3 (P = 0.005), but inversely correlated with IL-10 (P = 0.002). Copy number of Lactobacillus (P = 0.045) and Bifidobacterium (P = 0.011) showed correlation with IL-10 in IBS-C, while Gram-positive (P = 0.031) and Gram-negative bacteria (P = 0.010) showed correlation with CXCL-11 in IBS-D patients. Conclusions Altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a subset of patients with IBS.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.593-602
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• 2018

Background/Aims The different clinical manifestations of gastroesophageal reflux disease (GERD) may be influenced by associated psychological factors. We evaluated the psychological status (anxiety and depression) according to each subtype of GERD. Methods Subjects who underwent esophagogastroduodenoscopy and completed a symptom questionnaire between January 2008 and December 2011 were analyzed. The subjects were classified into the following groups: erosive reflux disease (ERD), non-erosive reflux disease (NERD), asymptomatic erosive esophagitis (AEE), and controls. Anxiety and depression were assessed using the State-Trait Anxiety Inventory and Beck Depression Inventory, respectively. Results We analyzed 19 099 subjects: 16 157 (84.6%), 176 (0.9%), 1398 (7.3%), and 1368 (7.2%) in the control, ERD, NERD, and AEE groups, respectively. Multiple multinomial logistic regression revealed a significant association of increased state (adjusted OR, 1.89; 95% CI, 1.53-2.33) and trait anxiety (adjusted OR, 1.78; 95% CI, 1.34-2.35) and depression (adjusted OR, 2.21; 95% CI, 1.75-2.80) with NERD. ERD group showed a significant association only with state anxiety (adjusted OR, 2.20; 95% CI, 1.27-3.81) and depression (adjusted OR, 2.23; 95% CI, 1.18-4.22). The AEE group, however, did not show any significant association with psychological factors. Conclusion This cross-sectional study revealed that anxiety and depression levels were significantly higher in subjects with GERD (notably in the NERD) than in controls.

• Health Policy and Management
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• v.29 no.2
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• pp.172-183
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• 2019

Background: Falls are the most frequent adverse events reported in hospitals. The aim of this study was to investigate the incidence rate and characteristics of falls in patients who used comprehensive nursing care service in National Health Insurance Service Ilsan Hospital. Methods: Incidence rate of falls was investigated in patients using comprehensive nursing care service, from July 2013 to Jun 2017 and compared with those not using this service. The characteristics and risk factors for falls, and fall-related injuries were obtained. Results: Among the 62,445 patients who used the comprehensive nursing care service for 4 years, total of 672 falls were reported. The incidence rate of falls per 1,000 patients-day was 1.15. The percentage of fall-related injuries was 26.9% and that of major injury was 2.2%. Although the incidence rate of all falls was slightly higher in patients using comprehensive nursing care service than those not using this service, falls-related injuries were not correlated with the implementation of this service. Conclusion: The falls could be more frequently detected and reported in comprehensive nursing care service, but there was no difference in fall-related injuries.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.414-422
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• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

• BMB Reports
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• v.55 no.2
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• pp.87-91
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• 2022

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

• Journal of Industrial Convergence
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• v.21 no.6
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• pp.37-42
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• 2023

This study aimed to examine the safety of HemoHIM, a dietary supplement containing methoxsalen. HemoHIM is a dietary supplement marketed globally, and a competitor to ginseng. It has been reported to contain methoxsalen, a plant extract for treating psoriasis and vitiligo. Methoxsalen is known to cause hepatotoxicity, but most of the cases has been reported from ingestion as a drug, not a food. There are no reports of hepatotoxicity from the consumption derived from natural products such as Angelica gigas, Cnidium officinale, and Paeonia lactiflora, which are the main ingredients in the HemoHIM. However, a recent case of acute hepatitis was reported in Hong-Kong after ingestion of HemoHIM. It is difficult to conclude that hepatitis was caused by HemoHIM, because there was no check of co-occurring medications with a higher risk of hepatotoxicity, no description of the progress, no quantitative comparison of methoxsalen in HemoHIM to it in common foods such as carrots and celery, and no description of the patient's underlying diseases. On the other hand, there was a study that suggest hemoHIM is safe, and that study had adequate number of subjects even though more studies are needed to ensure safety.

• Journal of Digestive Cancer Research
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• v.3 no.2
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• pp.82-88
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• 2015

Gastric lymphoma comprises 1-6% of all gastric malignant neoplasms and among them 50% is gastric MALT lymphoma. The 60-70% of MALT lymphomas is diagnosed at early, localized diseased state. Gastric MALT lymphoma is assumed that it progress slowly with indolent course. It presents nonspecific symptoms such as epigastric pain, dyspepsia, nausea and vomiting. It is rarely associated with serious complication such as gastrointestinal bleeding or perforation. The definite diagnosis of gastric MALT lymphoma should be made with histopathologically. Wotherspoon score is used to differential diagnosis with Helicobacter pylori associated gastric inflammatory change. Gastric MALT lymphoma is associated with Helicobacter pylori infection with supported by epidemiologic and histopathologic studies. Gastric MALT lymphoma is characterized with genetic aberrations such as trisomy 3, trisomy 18, chromosomal translocations t(11;18), t(1;14), t(14;18), t(3;14). Appropriate clinical staging is essential to determine the optimal treatment strategy for gastric MALT lymphoma. Lugano International Conference classification has been applied widely. Helicobacter pylori eradication is used as the first line treatment for gastric MALT lymphoma independent of the stage. The complete remission has been achieved in 60-90% of the stage I/II1 patients with Helicobacter pylori eradication only. The treatment options for the patients with refractory to eradication are radiotherapy, chemotherapy and/or immunotherapy with the complete remission rate of 75% to 100%. The incidence of gastric MALT lymphoma can be expected to down by virtue of the decrease of Helicobacter pylori infection rate. Further basic and clinical research is necessary to advance in determine the pathogenesis and management.

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.365-373
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• 2023

• Journal of Digestive Cancer Research
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• v.5 no.2
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• pp.86-90
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• 2017

Background: The aim of this study was to investigate clinicopathologic features of type 3 gastric neuroendocrine neoplasm (NEN) by treatment modality. Methods: The Korean Society of Gastrointestinal Cancer conducted the Korean Gastroenteropancreatic Neuroendocrine Tumor Registry, a retrospective registry database of gastroenteropancreatic neuroendocrine tumors from 16 hospitals in Korea. The normal serum gastrin level range was defined as <100 pg/mL, and gastric NEN patients with normal gastrin level were selected for analysis. Results: Among 358 patients with gastric NEN, 21 (5.9%) patients were classified with type 3 gastric NEN. The median age was 53 years (range 30-74). According to the WHO 2010 classification, 13 (61.9%) patients had grade 1, and 8 (38.1%) patients had grade 2 or 3. Endoscopic treatment was performed in 14 (66.7%) patients, and surgery was performed in 7 (33.3%) patients. The tumor size was smaller in the endoscopic treatment group than in the surgery group (0.6 cm vs 1.3 cm, p=0.006). After treatment, there was one recurrence in the surgery group. Conclusion: In small size Type 3 gastric NEN, endoscopic treatment was associated with a good prognosis, compared to surgery. Thus, endoscopic treatment can be used an alternative modality in selected cases of type 3 gastric NEN.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.1985-1995
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• 2021

Objective: Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis. Materials and Methods: A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007-2010). Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator. Results: After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; p < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; p < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, p < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, p < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B-C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh (p ≤ 0.045) and MELD (p ≤ 0.009) stratifications. Conclusion: The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosis.