• Title/Summary/Keyword: PPi

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Anti-inflammatory effect of sulforaphane on LPS-stimulated RAW 264.7 cells and ob/ob mice

  • Ranaweera, Sachithra S.;Dissanayake, Chanuri Y.;Natraj, Premkumar;Lee, Young Jae;Han, Chang-Hoon
    • Journal of Veterinary Science
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    • v.21 no.6
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    • pp.91.1-91.15
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    • 2020
  • Background: Sulforaphane (SFN) is an isothiocyanate compound present in cruciferous vegetables. Although the anti-inflammatory effects of SFN have been reported, the precise mechanism related to the inflammatory genes is poorly understood. Objectives: This study examined the relationship between the anti-inflammatory effects of SFN and the differential gene expression pattern in SFN treated ob/ob mice. Methods: Nitric oxide (NO) level was measured using a Griess assay. The inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were analyzed by Western blot analysis. Pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing analysis was performed to evaluate the differential gene expression in the liver of ob/ob mice. Results: The SFN treatment significantly attenuated the iNOS and COX-2 expression levels and inhibited NO, TNF-α, IL-1β, and IL-6 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA sequencing analysis showed that the expression levels of 28 genes related to inflammation were up-regulated (> 2-fold), and six genes were down-regulated (< 0.6-fold) in the control ob/ob mice compared to normal mice. In contrast, the gene expression levels were restored to the normal level by SFN. The protein-protein interaction (PPI) network showed that chemokine ligand (Cxcl14, Ccl1, Ccl3, Ccl4, Ccl17) and chemokine receptor (Ccr3, Cxcr1, Ccr10) were located in close proximity and formed a "functional cluster" in the middle of the network. Conclusions: The overall results suggest that SFN has a potent anti-inflammatory effect by normalizing the expression levels of the genes related to inflammation that were perturbed in ob/ob mice.

Clinical Features of Eosinophilic Esophagitis: A Single Center Experience in Ecuador

  • Munoz, Fabian Vasconez;Almeida, Pamela Hernandez;Carrion-Jaramillo, Estefania;Montalvo, Andrea Vasconez
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.4
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    • pp.293-299
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    • 2022
  • Purpose: Data on eosinophilic esophagitis (EoE) in South America is scarce. Moreover, no studies are available in Ecuador. We evaluated the clinical, endoscopic, and histological characteristics of Ecuadorian children with EoE. Methods: Medical records of 2,711 children who underwent upper gastrointestinal endoscopy (UGE) between 2009 and 2020 at Hospital Metropolitano de Quito, Ecuador were reviewed. Esophageal mucosal biopsies were obtained from 72 patients and the features of 35 children with EoE were described. EoE was diagnosed when there were more than 15 eosinophils in the esophagus, per high power field. Results: EoE was diagnosed in 35 children (9.4±4.5 years) with a male predominance (74%). Abdominal pain (51.4%) and vomiting (31.4%) were dominant symptoms. A history of allergic diseases was noted in 47.1% of the children, which mainly included allergic rhinitis (37.1%) and atopic dermatitis (11.4%). The most common endoscopic findings were furrowing (82.9%) and edema (74.3%). All patients were initially treated with proton-pump inhibitors (PPIs). Those who did not respond to PPIs received steroids (5.7%) and diet therapy (5.7%), and five patients were referred to an allergist. Clinical and histological resolution was observed in 65% of the patients who underwent a second UGE after 6-8 weeks of PPI. Conclusion: Our study describes the clinical features of pediatric EoE in Ecuador. This is the first retrospective study in Ecuador that describes the clinical, endoscopic, and histological manifestations of EoE in a small pediatric population. Almost half of the children who underwent a biopsy had EoE.

Integrative applications of network pharmacology and molecular docking: An herbal formula ameliorates H9c2 cells injury through pyroptosis

  • Zhongwen Qi;Zhipeng Yan;Yueyao Wang;Nan Ji;Xiaoya Yang;Ao Zhang;Meng Li;Fengqin Xu;Junping Zhang
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.228-236
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    • 2023
  • Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 μM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1β levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.

A Study on Changes in Industrial Value Added Response to Oil Prices in Korean (한국경제의 유가에 대한 산업부가가치 반응변화 연구)

  • Yoon Kyung Kim;Ji Whan Kim
    • Economic and Environmental Geology
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    • v.56 no.4
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    • pp.447-456
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    • 2023
  • Even after 2000, oil prices rose enough to be comparable to the past, but the impact on economic variables was relatively stable. Therefore, this study tries to empirically examine that the response of the Korean economy to oil prices has changed since the 1998 financial crisis, when there was a structural change in the Korean economy. Through empirical analysis, it was tested that the influence of oil prices and producer prices on consumer prices had changed in the period before and after 1998, and that the influence of producer prices on the value-added ratio by industry sector also changed. This means that the transfer of the increase in production cost to consumer prices has been alleviated, and the impact on added value has also been alleviated. Various studies should be conducted to understand the causes of the empirical results, such as changes in the relationship between producer prices and consumer prices, factors in the industrial sector due to rising oil prices, and changes in products.

A Study on Scholarly Communication Trends in Korean Library and Information Science Studies through Author Group Analysis (저자집단 분석을 통한 한국 문헌정보학의 학술커뮤니케이션 동향 연구)

  • Jae Yun Lee
    • Journal of the Korean Society for Library and Information Science
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    • v.57 no.2
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    • pp.409-434
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    • 2023
  • This study analyzes the authorship of all articles published in four domestic LIS journals over a 20-year period from 2002 to 2021 to examine the current status of scholarly communication through Korean LIS journals and suggest future prospects. To achieve this purpose, the study analyzed the number of co-authors, the proportion of returning authors, the publishing preference index (PPI), the author group change trend, and the researcher attraction index (RAI). The analysis revealed the level of collaborative research in each journal, the degree of formation of related author groups by journal, the inflection point of author group changes, the characteristics of emerging researchers, and the degree of author sharing between journals. Overall, 2015 was found to be an inflection point where the author community of Korean LIS journals changed. The newer generation of researchers showed a slightly different behavior of publishing papers than the older generation, as they mainly conduct collaborative research. These quantitative results could be triangulated with the qualitative interview data of previous studies to further strengthen the development strategy of Korean LIS journals.

Eosinophilic Esophagitis and Eosinophilic Gastroenteritis: Similarities and Differences

  • Yoshikazu Kinoshita;Norihisa Ishimura;Shunji Ishihara
    • Journal of Digestive Cancer Research
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    • v.6 no.1
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    • pp.1-5
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    • 2018
  • Eosinophilic gastrointestinal disease (EGID), a chronic allergic condition characterized by dense infiltration of eosinophils in the digestive tract, is classified into two types, eosinophilic esophagitis (EoE), which features dense infiltration of eosinophils in the esophageal epithelial layer, and eosinophilic gastroenteritis (EGE), in which the entire digestive tract including the esophagus may be involved. Patients with EoE only have esophageal symptoms, since the other parts of the digestive tract are not involved. On the other hand, 80% of EGE patients have lesions in the small intestine. The esophageal epithelial layer in healthy individuals has no or negligible infiltration by eosinophils, while the small intestinal mucosal layer, especially the distal small intestinal mucosa, can show dense eosinophil infiltration even in the absence of disease. Therefore, histological changes observed in cases of EGE are not qualitative but rather quantitative, as compared to EoE, which has qualitative histopathological changes, indicating important pathogenetic differences between the types. Comparisons of clinical, laboratory, and morphological characteristics between EoE and EGE have revealed several interesting differences. Both EoE and EGE patients are frequently affected by atopic diseases, such as bronchial asthma and allergic rhinitis, and elevated plasma levels of Th2 type cytokines and chemokines are also similarly seen in both. On the other hand, age at diagnosis differs, as the former is generally found in individuals from 30 to 50 years old, while the latter appears in all age groups. Additionally, 80% of patients with EoE are male as compared to only 50% of those with EGE. Furthermore, approximately 60% of patients with EoE respond favorably to proton pump inhibitor (PPI) administration, whereas EGE patients rarely show a response to PPIs. Nevertheless, both diseases show a similarly favorable response to a six foods elimination diet and glucocorticoid administration. These similarities and differences of EoE and EGE provide important clues for understanding the pathogenesis of these EGID types.

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Chemoquiescence with Molecular Targeted Ablation of Cancer Stem Cells in Gastrointestinal Cancers

  • Jong-Min Park;Young-Min Han;Migyeong Jeong;Eun Jin Go;Napapan Kangwan;Woo Sung Kim;Ki Baik Hahm
    • Journal of Digestive Cancer Research
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    • v.4 no.1
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    • pp.1-9
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    • 2016
  • The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.

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Study of the therapeutic mechanism of Zuojin Pill about functional dyspepsia through network pharmacology research (네트워크 약리학 연구를 통한 좌금환의 기능성 소화불량증 치료기전 연구)

  • Ju eun Lee;Na Ri Choi;Seung Hyeon Koo;Woo Gyun Choi;Byung Joo Kim
    • Herbal Formula Science
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    • v.32 no.3
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    • pp.247-261
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    • 2024
  • Objectives : Zuojin Pill, recognized as an effective herbal remedy, has undergone investigation for its potential in alleviating symptoms like indigestion, vomiting, and abdominal distension. The purpose of this study was to investigate the mechanism of digestive function activation through network pharmacology, particularly focused on improving functional dyspepsia. Methods : The two components, Coptidis Rhizoma and Evodiae Fructus, constituting Zuojin Pill were analyzed based on broad information on chemical and pharmacological properties, confirming 40 active compounds and 115 digestive-related molecular targets. Concentration analysis revealed impacts on various pathways related to digestive functions. Results : According to network pharmacological analysis of Zuojin Pill, quercetin and beta-sitosterol were exhibited relatively numerous targets, suggesting their potential significance in the therapeutic activity of Zuojin Pill and by a Protein-Protein Interaction (PPI) network, JUN, RELA, MAPK1, HSP90AA1, TP53, TNF, AKT1, IL6, MAPK14, ESR1, FOS, MYC were identified. Also, berberine exhibited the highest contribution index (92.58%), indicating that this compound may be a major contributor to the digestive activity of Zuojin Pill. Additionally, functional interaction analysis by GeneMANIA indicated that targets of Zuojin Pill could functionally interact through various mechanisms, implying similarities in pharmacological roles. Conclusions : These findings contribute valuable insights into the digestive function activation mechanism and highlight the therapeutic potential of Zuojin Pill in improving functional dyspepsia.

Effect of One- or Two-Week Triple Therapy with Omeprazole, Amoxicillin, and Clarithromycin on Eradication of Helicobacter pylori Infection in Children (소아에서 Omeprazole, Amoxicillin, Clarithromycin 삼제 병합 요법의 치료기간별 Helicobacter pylori 제균율)

  • Choi, In-Kyoung;Lee, Seung-Yun;Chung, Ki-Sup
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.5 no.1
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    • pp.19-25
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    • 2002
  • Purpose: The triple therapy with proton pump inhibitor (PPI) has been recognized as the treatment of choice in Helicobacter pylori (H. pylori) infection in adults. However, the effect of triple therapy with omeprazole, amoxicillin and clarithromycin (OAC) on eradication of H. pylori infection in children has not been established yet. This study was performed to evaluate the efficacy of OAC triple therapy and to compare the effect of one-week with two-week therapy on H. pylori eradication. Methods: From July 1998 to July 2000, 34 children with upper gastrointestinal symptoms, who underwent upper gastrointestinal endoscopy with biopsy at entry and 4 or more weeks after therapy, were enrolled in this study. H. pylori infection was assessed by CLO test and histologic examination (Hematoxylin-Eosin stain or Alcian yellow stain) with biopsy specimens. The regimen consisted of omeprazole (0.7 mg/kg/day), amoxicillin (50 mg/kg/day), and clarithromycin (25 mg/kg/day) for 1 week (n=21) or 2 weeks (n=13). Eradication of H. pylori was determined after the termination of treatment by the CLO test and histologic examination. Results: One-week treatment group consisted of 21 children (11 male, 10 female) with a mean age of $9.5{\pm}3.0$ years. Two-week group consisted of 13 children (4 male, 9 female) with a mean age of $9.9{\pm}4.0$ years. The endoscopic diagnoses included nodular gastritis in 19 cases, superficial gastritis in 7 cases, gastric ulcer in 4 cases, purpuric duodenitis in 2 cases, and normal in 2 cases. H. pylori was eradicated in 28 of total 34 children (82.4%). In 1-week group, H. pylori was eradicated in 17 of 21 children (81%). In 2-week group, H. pylori was eradicated in 11 of 13 children (84.6%). In remaining 6 cases in whom H. pylori had not been eradicated with OAC regimen, H. pylori infection persisted despite of the treatment with additional drugs such as colloidal bismuth subcitrate ($Denol^{(R)}$) and metronidazole. Conclusion: In this study, eradication rate of H. pylori with OAC regimen was 82.4%, and the triple therapy would be highly effective as primary treatment. However, there was no significant difference in the eradication rate between the 1-week and 2-week treatment group (P=0.785).

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Multi-Institute, Single Group, Prospective Observational Study to Evaluate the Efficacy of Mucomyst® in Relieving Symptoms of Globus Pharyngeus Refractory to Proton Pump Inhibitor (양성자펌프억제제에 반응하지 않는 인두이물감 환자에서 "뮤코미스트Mucomyst®" 객담제거 및 상기도 염증치료를 통한 증상개선효과 평가 다기관, 단일군, 전향적 관찰 연구)

  • Park, Hannah;Park, Il-Seok;Lee, Sang Hyuk;Lee, Seung-Won;Lee, Sang Joon;Lee, Byung-Joo;Cheon, Yong-Il;Park, Jun-Ook;Oh, Kyoung Ho;Shin, Yoo Seob
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.33 no.1
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    • pp.20-25
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    • 2022
  • Background and Objectives Globus pharyngeus is one of the most common symptoms of patients visiting otorhinolaryngology out-patient clinic, and usually long-lasting, difficult to treat, and frequently recurrent. Mucomyst®, N-acetyl cysteine is an inhalation agent mainly used for mucolysis and reducing inflammation in airway via antioxidative effect. The purpose of this study was to evaluate the efficacy of inhaled Mucomyst® treatment in patients with globus pharyngeus refractory to proton pump inhibitor (PPI). Materials and Method We prospectively evaluated the efficacy of Mucomyst® in relieving symptoms of globus pharyngeus refractory to PPI in nine medical centers. Three hundred and three patients enrolled and finally 229 patients finished the inhaled Mucomyst® therapy for 8 weeks. We analyzed the change of Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Visual Analogue Scale (VAS) for globus, and Globus Pharyngeus Symptom Scale (GPS) after use of Mucomyst® for 4 and 8 weeks. Results The GPS, RSI, RFS, and VAS score significantly decreased serially in patients who finished 8 week-inhalation treatment. The GPS improvement gap was significantly correlated with initial GPS (p<0.001) in multiple regression analysis. Conclusion Inhaled Mucomyst® therapy was effective for the reduction of both subjective and objective findings in refractory globus patients. This study might suggest new treatment option for patients with globus. However, further thorough studies would be needed to assess the real effect of inhaled Mucomyst® treatment as a standard treatment for globus.