|
1
|
Zhao X, Li F, Wen A, Yu X, Xu X, Wan C, Cao Y, Xin G, Huang W. Elucidating the mechanism of stigmasterol in acute pancreatitis treatment: insights from network pharmacology and in vitro/ in vivo experiments. Front Pharmacol 2024; 15:1485915. [PMID: 39764471 PMCID: PMC11701227 DOI: 10.3389/fphar.2024.1485915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Accepted: 12/09/2024] [Indexed: 03/17/2025] Open
Abstract
INTRODUCTION Acute pancreatitis (AP) is a severe inflammatory disease of the pancreas that could trigger a systemic inflammation and multi-organ dysfunction. Stigmasterol, a natural plant sterol found in various herbs and vegetables, exhibits a significant anti-inflammatory, antioxidant, and cholesterol-lowering effects. However, its therapeutic potential in AP have not been thoroughly investigated. METHODS The present study employed network pharmacology combined with experimental verification to explore the protective effect of stigmasterol on AP and its molecular mechanism in a sodium taurocholate (STC)-induced AP mouse model. RESULTS Protein-protein interaction (PPI) analysis pinpointed out MAPK3, also named as ERK1, as a promising stigmasterol target in AP therapy. Molecular docking analysis further revealed a strong binding capacity of stigmasterol to ERK1 (-6.57 kL/mol). Furthermore, both in vivo and in vitro studies demonstrated that stigmasterol treatment notably attenuated STC-induced pancreatic injury, as evidented by decreased serum levels of lipase and amylase, improved systemic inflammation, and reduced acinar cell necrosis. At the molecular level, stigmasterol treatment exhibited a significant inhibition on STC-induced activation of ERK signaling pathway in pancreatic acinar cells, leading to the transition of acinar cell death from necrosis to apoptosis, thereby preventing acinar cell necrosis-induced systemic inflammation. CONCLUSION This study demonstrated that stigmasterol exhibits a significant protective effect aganist AP, at least in part through enhancing acinar cell apoptosis via modulating the ERK signaling pathways.
Collapse
Affiliation(s)
- Xuanlin Zhao
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Fan Li
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Ao Wen
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xiuxian Yu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xinrui Xu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Chengyu Wan
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yu Cao
- Department of Emergency Medicine, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Guang Xin
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Wen Huang
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
2
|
Tsomidis I, Voumvouraki A, Kouroumalis E. The Pathogenesis of Pancreatitis and the Role of Autophagy. GASTROENTEROLOGY INSIGHTS 2024; 15:303-341. [DOI: 10.3390/gastroent15020022] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
The pathogenesis of acute and chronic pancreatitis has recently evolved as new findings demonstrate a complex mechanism operating through various pathways. In this review, the current evidence indicating that several mechanisms act in concert to induce and perpetuate pancreatitis were presented. As autophagy is now considered a fundamental mechanism in the pathophysiology of both acute and chronic pancreatitis, the fundamentals of the autophagy pathway were discussed to allow for a better understanding of the pathophysiological mechanisms of pancreatitis. The various aspects of pathogenesis, including trypsinogen activation, ER stress and mitochondrial dysfunction, the implications of inflammation, and macrophage involvement in innate immunity, as well as the significance of pancreatic stellate cells in the development of fibrosis, were also analyzed. Recent findings on exosomes and the miRNA regulatory role were also presented. Finally, the role of autophagy in the protection and aggravation of pancreatitis and possible therapeutic implications were reviewed.
Collapse
Affiliation(s)
- Ioannis Tsomidis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
| | - Argyro Voumvouraki
- 1st Department of Internal Medicine, AHEPA University Hospital, 54621 Thessaloniki, Greece
| | - Elias Kouroumalis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Crete, Greece
| |
Collapse
|
|
3
|
Han Z, Li J, Yi X, Zhang T, Liao D, You J, Ai J. Diagnostic accuracy of interleukin-6 in multiple diseases: An umbrella review of meta-analyses. Heliyon 2024; 10:e27769. [PMID: 38515672 PMCID: PMC10955306 DOI: 10.1016/j.heliyon.2024.e27769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 03/06/2024] [Accepted: 03/06/2024] [Indexed: 03/23/2024] Open
Abstract
Objective This review aims to conduct a comprehensive study of the diagnostic accuracy of interleukin-6 (IL-6) for multiple diseases by utilizing existing systematic reviews and meta-analyses. Methods We performed a thorough search of Embase, Web of Science, PubMed, and Cochrane Database of Systematic Reviews up to April 2023 to gather meta-analyses that investigate the diagnostic accuracy of IL-6. To assess the methodological quality of the studies, we employed the Assessing the Methodological Quality of Systematic Reviews-2 and Grading of Recommendations, Assessment, Development and Evaluation criteria. Results We included 34 meta-analyses out of the 3024 articles retrieved from the search. These meta-analyses covered 9 categories of diseases of the International Classification of Diseases-11. Studies rated as "Critically Low" or "Very Low" in the quality assessment process were excluded, resulting in a total of 6 meta-analyses that encompassed sepsis, colorectal cancer, tuberculous pleural effusion (TPE), endometriosis, among others. Among these diseases, IL-6 demonstrated a relatively high diagnostic potential in accurately identifying TPE and endometriosis. Conclusions IL-6 exhibited favorable diagnostic accuracy across multiple diseases, suggesting its potential as a reliable diagnostic biomarker in the near future. Substantial evidence supported its high diagnostic accuracy, particularly in the cases of TPE and endometriosis.
Collapse
Affiliation(s)
| | | | | | - Tianyi Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu, 610041, PR China
| | - Dazhou Liao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu, 610041, PR China
| | - Jia You
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu, 610041, PR China
| | - Jianzhong Ai
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu, 610041, PR China
| |
Collapse
|
|
4
|
Yang H, Liu Y, Yao J, Wang Y, Wang L, Ren P, Bai B, Wen Q. Mesenchymal stem cells inhibit ferroptosis by activating the Nrf2 antioxidation pathway in severe acute pancreatitis-associated acute lung injury. Eur J Pharmacol 2024; 967:176380. [PMID: 38311279 DOI: 10.1016/j.ejphar.2024.176380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/24/2024] [Accepted: 02/01/2024] [Indexed: 02/10/2024]
Abstract
Severe acute pancreatitis-associated acute lung injury (SAP-ALI) remains a significant challenge for healthcare practitioners because of its high morbidity and mortality; therefore, there is an urgent need for an effective treatment. Mesenchymal stem cells (MSCs) have shown significant potential in the treatment of a variety of refractory diseases, including lung diseases. This study aimed to investigate the protective effects of MSCs against SAP-ALI and its underlying mechanisms. Our results suggest that MSCs mitigate pathological injury, hemorrhage, edema, inflammatory response in lung tissue, and lipopolysaccharide (LPS)-induced cell damage in RLE-6TN cells (a rat alveolar epithelial cell line). The results also showed that MSCs, similar to the effects of ferrostatin-1 (ferroptosis inhibitor), suppressed the ferroptosis response, which was manifested as down-regulated Fe2+, malondialdehyde, and reactive oxygen species (ROS) levels, and up-regulated glutathione peroxidase 4 (GPX4) and glutathione (GSH) levels in vivo and in vitro. The activation of ferroptosis by erastin (a ferroptosis agonist) reversed the protective effect of MSCs against SAP-ALI. Furthermore, MSCs activated the nuclear factor erythroid 2 associated factor 2 (Nrf2) transcription factor, and blocking the Nrf2 signaling pathway with ML385 abolished the inhibitory effect of MSCs on ferroptosis in vitro. Collectively, these results suggest that MSCs have therapeutic effects against SAP-ALI. The specific mechanism involves inhibition of ferroptosis by activating the Nrf2 transcription factor.
Collapse
Affiliation(s)
- Hongfang Yang
- Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China; Department of Anesthesiology, Dalian University Affiliated Xinhua Hospital, Dalian, China
| | - Yan Liu
- Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China; Anesthesiology Department, Dalian Medical University, Dalian, China
| | - Jiaqi Yao
- Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yin Wang
- Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University, Xian, China
| | - Lihong Wang
- Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Penghui Ren
- Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China; Anesthesiology Department, Dalian Medical University, Dalian, China
| | - Buyue Bai
- Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China; Anesthesiology Department, Dalian Medical University, Dalian, China
| | - Qingping Wen
- Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
| |
Collapse
|
|
5
|
Song Y, Lee SH. Recent Treatment Strategies for Acute Pancreatitis. J Clin Med 2024; 13:978. [PMID: 38398290 PMCID: PMC10889262 DOI: 10.3390/jcm13040978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/26/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Acute pancreatitis (AP) is a leading gastrointestinal disease that causes hospitalization. Initial management in the first 72 h after the diagnosis of AP is pivotal, which can influence the clinical outcomes of the disease. Initial management, including assessment of disease severity, fluid resuscitation, pain control, nutritional support, antibiotic use, and endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis, plays a fundamental role in AP treatment. Recent updates for fluid resuscitation, including treatment goals, the type, rate, volume, and duration, have triggered a paradigm shift from aggressive hydration with normal saline to goal-directed and non-aggressive hydration with lactated Ringer's solution. Evidence of the clinical benefit of early enteral feeding is becoming definitive. The routine use of prophylactic antibiotics is generally limited, and the procalcitonin-based algorithm of antibiotic use has recently been investigated to distinguish between inflammation and infection in patients with AP. Although urgent ERCP (within 24 h) should be performed for patients with gallstone pancreatitis and cholangitis, urgent ERCP is not indicated in patients without cholangitis. The management approach for patients with local complications of AP, particularly those with infected necrotizing pancreatitis, is discussed in detail, including indications, timing, anatomical considerations, and selection of intervention methods. Furthermore, convalescent treatment, including cholecystectomy in gallstone pancreatitis, lipid-lowering medications in hypertriglyceridemia-induced AP, and alcohol intervention in alcoholic pancreatitis, is also important for improving the prognosis and preventing recurrence in patients with AP. This review focuses on recent updates on the initial and convalescent management strategies for AP.
Collapse
Affiliation(s)
| | - Sang-Hoon Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul 05030, Republic of Korea;
| |
Collapse
|
|
6
|
Zhou L, Yu J, Wang S, Ma Y, Liu X, Zhang X, Luo Y, Wen S, Li L, Li W, Niu X. Tectoridin alleviates caerulein-induced severe acute pancreatitis by targeting ERK2 to promote macrophage M2 polarization. Arch Biochem Biophys 2024; 752:109873. [PMID: 38141907 DOI: 10.1016/j.abb.2023.109873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 12/07/2023] [Accepted: 12/16/2023] [Indexed: 12/25/2023]
Abstract
Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.
Collapse
Affiliation(s)
- Lili Zhou
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Jinjin Yu
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Siqi Wang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Yajing Ma
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Xinyao Liu
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Xinya Zhang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Yuzhi Luo
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Sha Wen
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Lingli Li
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China
| | - Weifeng Li
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China.
| | - Xiaofeng Niu
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, PR China.
| |
Collapse
|
|
7
|
Zhang R, Yin M, Jiang A, Zhang S, Xu X, Liu L. Automated machine learning for early prediction of acute kidney injury in acute pancreatitis. BMC Med Inform Decis Mak 2024; 24:16. [PMID: 38212745 PMCID: PMC10785491 DOI: 10.1186/s12911-024-02414-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 01/01/2024] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND Acute kidney injury (AKI) represents a frequent and grave complication associated with acute pancreatitis (AP), substantially elevating both mortality rates and the financial burden of hospitalization. The aim of our study is to construct a predictive model utilizing automated machine learning (AutoML) algorithms for the early prediction of AKI in patients with AP. METHODS We retrospectively analyzed patients who were diagnosed with AP in our hospital from January 2017 to December 2021. These patients were randomly allocated into a training set and a validation set at a ratio of 7:3. To develop predictive models for each set, we employed the least absolute shrinkage and selection operator (LASSO) algorithm along with AutoML. A nomogram was developed based on multivariate logistic regression analysis outcomes. The model's efficacy was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Additionally, the performance of the model constructed via AutoML was evaluated using decision curve analysis (DCA), feature importance, SHapley Additive exPlanations (SHAP) plots, and locally interpretable model-agnostic explanations (LIME). RESULTS This study incorporated a total of 437 patients who met the inclusion criteria. Out of these, 313 were assigned to the training cohort and 124 to the validation cohort. In the training and validation cohorts, AKI occurred in 68 (21.7%) and 29(23.4%) patients, respectively. Comparative analysis revealed that the AutoML models exhibited enhanced performance over traditional logistic regression (LR). Furthermore, the deep learning (DL) model demonstrated superior predictive accuracy, evidenced by an area under the ROC curve of 0.963 in the training set and 0.830 in the validation set, surpassing other comparative models. The key variables identified as significant in the DL model within the training dataset included creatinine (Cr), urea (Urea), international normalized ratio (INR), etiology, smoking, alanine aminotransferase (ALT), hypertension, prothrombin time (PT), lactate dehydrogenase (LDH), and diabetes. CONCLUSION The AutoML model, utilizing DL algorithm, offers considerable clinical significance in the early detection of AKI among patients with AP.
Collapse
Affiliation(s)
- Rufa Zhang
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Changshu NO.1 People's Hospital, No. 1 Shuyuan Street, 215500, Suzhou, Jiangsu, China
| | - Minyue Yin
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Anqi Jiang
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Changshu NO.1 People's Hospital, No. 1 Shuyuan Street, 215500, Suzhou, Jiangsu, China
| | - Shihou Zhang
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Changshu NO.1 People's Hospital, No. 1 Shuyuan Street, 215500, Suzhou, Jiangsu, China
| | - Xiaodan Xu
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Changshu NO.1 People's Hospital, No. 1 Shuyuan Street, 215500, Suzhou, Jiangsu, China.
| | - Luojie Liu
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, Changshu NO.1 People's Hospital, No. 1 Shuyuan Street, 215500, Suzhou, Jiangsu, China.
| |
Collapse
|
|
8
|
Zhao W. Immune-Related Genes can Serve as Potential Biomarkers for Predicting Severe Acute Pancreatitis. Horm Metab Res 2023; 55:711-721. [PMID: 37391177 DOI: 10.1055/a-2105-6152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/02/2023]
Abstract
We aimed to investigate immune-related candidate genes for predicting the severity of acute pancreatitis (AP). RNA sequencing profile GSE194331 was downloaded, and differentially expressed genes (DEGs) were investigated. Meanwhile, the infiltration of immune cells in AP were assessed using CIBERSORT. Genes related with the infiltration of immune cells were investigated using weighted gene co-expression network analysis (WGCNA). Furthermore, immune subtypes, micro-environment, and DEGs between immune subtypes were explored. Immune-related genes, protein-protein interaction (PPI) network, and functional enrichment analysis were further performed. Overall, 2533 DEGs between AP and healthy controls were obtained. After trend cluster analysis, 411 upregulated and 604 downregulated genes were identified. Genes involved in two modules were significantly positively related to neutrophils and negatively associated with T cells CD4 memory resting, with correlation coefficient more than 0.7. Then, 39 common immune-related genes were obtained, and 56 GO BP were enriched these genes, including inflammatory response, immune response, and innate immune response; 10 KEGG pathways were enriched, including cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, and IL-17 signaling pathway. Genes, including S100A12, MMP9, IL18, S100A8, HCK, S100A9, RETN, OSM, FGR, CAMP, were selected as genes with top 10 degree in PPI, and the expression levels of these genes increased gradually in subjects of healthy, mild, moderately severe, and severe AP. Our findings indicate a central role of immune-related genes in predicting the severity of AP, and the hub genes involved in PPI represent logical candidates for further study.
Collapse
Affiliation(s)
- Weijuan Zhao
- Emergency, Affiliated Wuxi Fifth Hospital of Jiangnan University (Infectious Diseases Hospital of Wuxi), Wuxi, China
| |
Collapse
|
|
9
|
Cho IR, Do MY, Han SY, Jang SI, Cho JH. Comparison of Interleukin-6, C-Reactive Protein, Procalcitonin, and the Computed Tomography Severity Index for Early Prediction of Severity of Acute Pancreatitis. Gut Liver 2023; 17:629-637. [PMID: 36789576 PMCID: PMC10352050 DOI: 10.5009/gnl220356] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 11/11/2022] [Accepted: 11/23/2022] [Indexed: 02/16/2023] Open
Abstract
Background/Aims Acute pancreatitis (AP) is a common gastrointestinal disease associated with hospitalization. With the increase in its incidence, AP has become a greater burden on healthcare resources. Early identification of patients with mild AP can facilitate the appropriate use of resources. We aimed to investigate the ability of inflammatory markers, including interleukin-6 (IL-6), procalcitonin, and C-reactive protein (CRP), as well as various scoring systems to differentiate mild AP from more severe diseases. Methods We retrospectively investigated patients hospitalized with AP, for whom severity assessment and clinical course confirmation were possible. Inflammatory markers were measured at admission, and CRP levels were measured 24 hours after admission (CRP2). Predictive values were calculated using the area under the receiver operating characteristic curve (AUROC) and logistic regression model analysis. Results Of 103 patients with AP, 42 (40.8%) were diagnosed with mild AP according to the revised Atlanta classification. Based on the AUROC, IL-6 (0.755, p<0.001), CRP2 (0.787, p<0.001), and computed tomography severity index (CTSI) (0.851, p<0.001) were useful predictors of mild AP. With standard cutoff values, the diagnostic sensitivity, specificity, and accuracy were 83.3%, 62.3%, and 70.9% for IL-6 (<50 pg/mL), and 78.6%, 63.9%, and 69.9% for CRP2 (<50 mg/L), respectively. The AUROC of IL-6 and CRP2 were significantly higher than those of other inflammatory markers and were not significantly different from that of CTSI. Conclusions IL-6, CRP2, and CTSI are helpful for early differentiation of AP severity. Among inflammatory markers, IL-6 has the advantage of early prediction of mild pancreatitis at the time of admission.
Collapse
Affiliation(s)
- In Rae Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, and
| | - Min Young Do
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - So Young Han
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Ill Jang
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cho
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
10
|
Zhang Y, Long Y, Wan J, Liu S, Shi A, Li D, Yu S, Li X, Wen J, Deng J, Ma Y, Li N. Macrophage membrane biomimetic drug delivery system: for inflammation targeted therapy. J Drug Target 2023; 31:229-242. [PMID: 35587560 DOI: 10.1080/1061186x.2022.2071426] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
In recent years, there have been many exciting developments in the biomedical applications of the macrophage membrane bionic drug delivery system (MM-Bio-DDS). Macrophages, as an important immune cell, are involved in initiating and regulating the specific immune response of the body. Therefore, the inflammatory process related to macrophages is an important goal in the diagnosis and treatment of many diseases. In this review, we first summarise the different methods of preparation, characterisation, release profiles and natural advantages of using macrophages as a drug delivery system (DDS). Second, we introduce the processes of various chronic inflammatory diseases and the role of macrophages in them, specifically clarifying how the MM-Bio-DDS provides a wide and effective treatment for the targeted inflammatory site. Finally, based on the existing research, we propose the application prospect and existing challenges of the MM-Bio-DDS, especially the problems in clinical transformation, to provide new ideas for the development and utilisation of the MM-Bio-DDS in targeted drug delivery for inflammation and the treatment of diseases.
Collapse
Affiliation(s)
- Yulu Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu Long
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinyan Wan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Songyu Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ai Shi
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Dan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shuang Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaoqiu Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jing Wen
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jie Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yin Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Nan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
11
|
Wang X, Qian J, Meng Y, Wang P, Cheng R, Zhou G, Zhu S, Liu C. Salidroside ameliorates severe acute pancreatitis-induced cell injury and pyroptosis by inactivating Akt/NF-κB and caspase-3/GSDME pathways. Heliyon 2023; 9:e13225. [PMID: 36747537 PMCID: PMC9898447 DOI: 10.1016/j.heliyon.2023.e13225] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 01/12/2023] [Accepted: 01/20/2023] [Indexed: 01/30/2023] Open
Abstract
Our previous studies showed that Salidroside (Sal), a glucoside of the phenylpropanoid tyrosol isolated from Rhodiola rosea L, alleviated severe acute pancreatitis (SAP) by inhibiting inflammation. However, the detailed mechanism remains unclear. Recent evidence has indicated a critical role of Sal in ameliorating inflammatory disorders by regulating pyroptosis. The present study aimed to explore the involvement of Sal and pyroptosis in the pathogenesis of SAP and investigate the potential mechanism. The effects of Sal on pyroptosis were first evaluated using SAP rat and cell model. Our results revealed that Sal treatment significantly decreased SAP-induced pancreatic cell damage and pyroptosis in vivo and in vitro, as well as reduced the release of lactate dehydrogenase (LDH), IL-1β and IL-18. Search Tool for Interacting Chemicals (STITCH) online tool identified 4 genes (CASP3, AKT1, HIF1A and IL10) as candidate targets of Sal in both rattus norvegicus and homo sapiens. Western blot and immunohistochemistry staining validated that Sal treatment decreased the phosphorylation levels of Akt and NF-κB p65, as well as cleaved caspase-3 and N-terminal fragments of GSDME (GSDME-N), suggesting that Sal might suppress pyroptosis through inactivating Akt/NF-κB and Caspase-3/GSDME pathways. Furthermore, overexpression of AKT1 or CASP3 could partially reverse the inhibitory effects of Sal on cell injury and pyroptosis, while downregulation of AKT1 or CASP3 promoted the inhibitory effects of Sal. Taken together, our data indicate that Sal suppresses SAP-induced pyroptosis through inactivating Akt/NF-κB and Caspase-3/GSDME pathways.
Collapse
Affiliation(s)
- Xiaohong Wang
- Department of Gastroenterology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211900, Jiangsu, China,Corresponding author.
| | - Jing Qian
- Department of General Surgery, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211900, Jiangsu, China
| | - Yun Meng
- Department of Gastroenterology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211900, Jiangsu, China
| | - Ping Wang
- Department of Gastroenterology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211900, Jiangsu, China
| | - Ruizhi Cheng
- Department of Gastroenterology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211900, Jiangsu, China
| | - Guoxiong Zhou
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China
| | - Shunxing Zhu
- Laboratory Animal Center of Nantong University, Nantong, 226001, Jiangsu, China
| | - Chun Liu
- Laboratory Animal Center of Nantong University, Nantong, 226001, Jiangsu, China
| |
Collapse
|
|
12
|
Gao Y, Gao Y, Niu Z, Liu J, Feng H, Sun J, Wang L, Pan L. CCCTC-binding factor-mediated microRNA-340-5p suppression aggravates myocardial injury in rats with severe acute pancreatitis through activation of the HMGB1/TLR4 axis. Immunopharmacol Immunotoxicol 2022; 44:306-315. [PMID: 35238277 DOI: 10.1080/08923973.2022.2043898] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 02/13/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Severe acute pancreatitis (SAP) is a life-threatening disorder associated with multisystem organ failure. This study aimed to investigate the function of high mobility group box 1 (HMGB1) in SAP-induced myocardial injury. METHODS A rat model with SAP was induced. The pathological changes in rat pancreatic and cardiac tissues were examined by HE staining. Cardiomyocyte apoptosis in rat cardiac tissues, and the serum levels of myocardial injury markers and pro-inflammatory cytokines were examined. Rat primary cardiomyocytes were treated with H2O2 for in vitro experiments. The regulatory molecules of HMGB1 were predicted by bioinformatics analysis. Altered expression of HMGB1, microRNA (miR)-340-5p and CCCTC-binding factor (CTCF) was introduced in rats or cells to investigate their roles in myocardial injury. RESULTS CTCF and HMGB1 were highly expressed but miR-340-5p was poorly expressed in cardiac tissues of rats with SAP. HMGB1 silencing reduced toll-like receptor 4 (TLR4) expression to promote proliferation and reduce apoptosis of H2O2-treated cardiomyocytes. miR-340-5p targeted HMGB1 mRNA, while CTCF suppressed miR-340-5p transcription. CTCF upregulation or miR-340-5p downregulation blocked the effects of HMGB1 silencing on cardiomyocytes. In vivo, CTCF silencing alleviated injury in rat pancreatic and cardiac tissues and reduced the expression of creatine kinase-MB (CK-MB), lactic dehydrogenase, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in rat serum. But further overexpression of HMGB1 or inhibition of miR-340-5p aggravated the symptoms in rats. CONCLUSION This study demonstrated that CTCF reduces transcription of miR-340-5p to promote HMGB1 expression, which activates TLR4 expression and promotes myocardial injury in rats with SAP.
Collapse
Affiliation(s)
- Yazhou Gao
- Department of Emergency Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Yanxia Gao
- Department of Emergency Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Zequn Niu
- Department of Emergency Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Jie Liu
- Department of Emergency Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Hui Feng
- Department of Emergency Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Jiangli Sun
- Department of Emergency Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Liming Wang
- Department of Emergency Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| | - Longfei Pan
- Department of Emergency Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China
| |
Collapse
|
|
13
|
Lee PJ, Papachristou GI. Early Prediction of Severity in Acute Pancreatitis. CLINICAL PANCREATOLOGY FOR PRACTISING GASTROENTEROLOGISTS AND SURGEONS 2021:31-39. [DOI: 10.1002/9781119570097.ch4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
14
|
Xu Q, Wang M, Guo H, Liu H, Zhang G, Xu C, Chen H. Emodin Alleviates Severe Acute Pancreatitis-Associated Acute Lung Injury by Inhibiting the Cold-Inducible RNA-Binding Protein (CIRP)-Mediated Activation of the NLRP3/IL-1 β/CXCL1 Signaling. Front Pharmacol 2021; 12:655372. [PMID: 33967799 PMCID: PMC8103163 DOI: 10.3389/fphar.2021.655372] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 02/23/2021] [Indexed: 12/12/2022] Open
Abstract
Objective: Severe acute pancreatitis (SAP) can lead to acute lung injury (ALI). This study investigated the therapeutic effect of emodin and its molecular mechanisms in a rat model of SAP-ALI. Methods: Forty male Sprague-Dawley rats were randomly divided into the groups: Control (CON), SAP (SAP), emodin (EMO), and C23 (C23). The latter three groups of rats were induced for SAP-ALI by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct and were treated with vehicle, emodin or C23, respectively. One day post induction, their pancreatic and lung injury was assessed by histology and arterial blood gas analysis. In vitro, rat alveolar macrophages (NR8383 cells) were treated with recombinant rat CIRP in the presence or absence of TAK242 (a TLR4 inhibitor), C23 or emodin. The CIRP-mediated activation of the NLRP3/IL-1β/CXCL1 signaling in rat lungs and NR8383 cells was determined. Similarly, the role of IL-1β in the CIRP-induced CXCL1 expression was investigated. Results: Emodin treatment significantly reduced inflammation and tissue damages in the pancreatic and lung tissues in rats with SAP-ALI, accompanied by decreasing serum amylase, CIRP and IL-1β levels and improving lung function. Furthermore, emodin significantly mitigated the SAP-up-regulated CIRP expression in the pancreatic islets and lung tissues, and attenuated the SAP-activated NF-κB signaling, NLRP3 inflammasome formation and CXCL1 expression in lung resident macrophages as well as neutrophil infiltration in the lungs of rats. In addition, treatment with CIRP significantly activated the NF-κB signaling and NLRP3 inflammasome formation and induced IL-1β and CXCL1 expression and pyroptosis in NR8383 cells, which were abrogated by TAK242 and significantly mitigated by C23 or emodin. Moreover, CIRP only induced very lower levels of CXCL1 expression in IL-1β-silencing NR8383 cells and treatment with IL-1β induced CXCL1 expression in NR8383 cells in a dose and time-dependent manner. Conclusion: Emodin may inhibit the CIRP-activated NLRP3/IL-1β/CXCL1signaling to decrease neutrophil infiltration and ameliorate the SAP-ALI in rats.
Collapse
Affiliation(s)
- Qiushi Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Mengfei Wang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Haoya Guo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Huanhuan Liu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Caiming Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.,Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| |
Collapse
|
|
15
|
Qu C, Gao L, Yu XQ, Wei M, Fang GQ, He J, Cao LX, Ke L, Tong ZH, Li WQ. Machine Learning Models of Acute Kidney Injury Prediction in Acute Pancreatitis Patients. Gastroenterol Res Pract 2020; 2020:3431290. [PMID: 33061958 PMCID: PMC7542489 DOI: 10.1155/2020/3431290] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 08/19/2020] [Accepted: 09/06/2020] [Indexed: 12/20/2022] Open
Abstract
Background. Acute kidney injury (AKI) has long been recognized as a common and important complication of acute pancreatitis (AP). In the study, machine learning (ML) techniques were used to establish predictive models for AKI in AP patients during hospitalization. This is a retrospective review of prospectively collected data of AP patients admitted within one week after the onset of abdominal pain to our department from January 2014 to January 2019. Eighty patients developed AKI after admission (AKI group) and 254 patients did not (non-AKI group) in the hospital. With the provision of additional information such as demographic characteristics or laboratory data, support vector machine (SVM), random forest (RF), classification and regression tree (CART), and extreme gradient boosting (XGBoost) were used to build models of AKI prediction and compared to the predictive performance of the classic model using logistic regression (LR). XGBoost performed best in predicting AKI with an AUC of 91.93% among the machine learning models. The AUC of logistic regression analysis was 87.28%. Present findings suggest that compared to the classical logistic regression model, machine learning models using features that can be easily obtained at admission had a better performance in predicting AKI in the AP patients.
Collapse
Affiliation(s)
- Cheng Qu
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lin Gao
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Xian-qiang Yu
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Clinical Medical College of Southeast University, Nanjing, China
| | - Mei Wei
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guo-quan Fang
- Electrical Engineering School of Southeast University, China
| | - Jianing He
- Institute for Hospital Management of Tsinghua University, Shenzhen, China
| | - Long-xiang Cao
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lu Ke
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Zhi-hui Tong
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Wei-qin Li
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| |
Collapse
|
|
16
|
Atherogenic Index of Plasma Is a Potential Biomarker for Severe Acute Pancreatitis: A Prospective Observational Study. J Clin Med 2020; 9:jcm9092982. [PMID: 32942753 PMCID: PMC7565847 DOI: 10.3390/jcm9092982] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/11/2020] [Accepted: 09/14/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The atherogenic index of plasma (AIP) reflects the levels of triglycerides (TG) and high-density lipoprotein (HDL) cholesterol. The purpose of this study was to assess the relationship between the AIP and severe acute pancreatitis (SAP). MATERIALS AND METHODS Patients with acute pancreatitis (AP) were prospectively enrolled from March 2015 to June 2019. The severity of AP was classified according to the 2012 revised Atlanta classification. Mild and moderately severe AP were categorized as non-SAP. The AIP is calculated as log(TG/HDL). RESULTS A total of 323 patients were enrolled. The etiologies of AP were gallstone in 171 patients (52.9%), alcohol in 122 patients (37.8%), and hypertriglyceridemia in 30 patients (9.3%). Twenty-four patients (7.4%) were classified as SAP. The AIP was significantly higher in the SAP group compared to the non-SAP group (p < 0.001). The AIP was positively correlated with the Atlanta classification (R = 0.256, p < 0.001). In multivariate analysis, the AIP was found to be an independent predictive factor for SAP (OR = 4.571; CI = 1.913-10.922; p = 0.001). CONCLUSIONS The AIP is a potential biomarker for the prediction of SAP in clinical practice. This result provides that impaired lipid metabolism is associated with the severity of pancreatitis.
Collapse
|
|
17
|
Fan HN, Chen W, Fan LN, Wu JT, Zhu JS, Zhang J. Macrophages-derived p38α promotes the experimental severe acute pancreatitis by regulating inflammation and autophagy. Int Immunopharmacol 2019; 77:105940. [PMID: 31655340 DOI: 10.1016/j.intimp.2019.105940] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 09/23/2019] [Accepted: 09/26/2019] [Indexed: 01/19/2023]
Abstract
BACKGROUND Severe acute pancreatitis (SAP) is a common threat to human health. In the present study, we aimed to investigate the underlying mechanisms by which p38α in macrophages contributes to SAP. We used conditional knockout of p38α in macrophages and p38 MAPK inhibitors to understand the effects of p38α in macrophages on caerulein-induced inflammatory responses in SAP mice models. METHODS AND MATERIALS Wild-type (WT) mice were randomly divided into three groups: a control group, SAP group, and SAP + p38MAPK inhibitor (SB203580) group, and mice with a conditional knockout (KO) of p38α in macrophages were included in a KO + SAP group. We evaluated pancreatic pathology and ultra-structure by hematoxylin and eosin staining and transmission electron microscopy. The pulmonary wet-to-dry weight ratio was calculated. The serum levels of TNF-α and IL-1β were determined by ELISA. The mRNA and protein expression of inflammatory cytokines TNF-α, IL-1β, IL-17, IL-18, MIF, and MCP-1 in pancreatic tissues were tested by qRT-PCR and immunohistochemistry analysis. The protein expression of p38, caspase-1, ULK1, LC3B and p62 in pancreatic tissues was examined by Western blotting. RESULTS The results indicated that the severity of SAP as well as the expression of the cytokines TNF-α, IL-1β, IL-17, IL-18 and MCP-1 were higher in the SAP group than those in the control group, but were lower in the SAP + SB203580 and KO + SAP groups as compared with the SAP group. The protein expression of p38, caspase-1, LC3B and p62 was increased in the SAP group than that in the control group, but this result was reversed in the SAP + SB203580 and KO + SAP groups as compared with the SAP group. In addition, the ULK1 level was significantly lower in the SAP group than that in the control group, but was increased in the SAP + SB203580 and KO + SAP groups as compared with the SAP group. CONCLUSIONS Our findings demonstrated that, macrophage derived p38α promoted the experimental severe acute pancreatitis by regulating inflammation and autophagy.
Collapse
Affiliation(s)
- Hui-Ning Fan
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Wei Chen
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Li-Na Fan
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen 361004, China
| | - Jing-Tong Wu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China
| | - Jin-Shui Zhu
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
| | - Jing Zhang
- Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
| |
Collapse
|
|
18
|
Abstract
The incidence of acute pancreatitis continues to increase worldwide, and it is one of the most common gastrointestinal causes for hospital admission in the USA. In the past decade, substantial advancements have been made in our understanding of the pathophysiological mechanisms of acute pancreatitis. Studies have elucidated mechanisms of calcium-mediated acinar cell injury and death and the importance of store-operated calcium entry channels and mitochondrial permeability transition pores. The cytoprotective role of the unfolded protein response and autophagy in preventing sustained endoplasmic reticulum stress, apoptosis and necrosis has also been characterized, as has the central role of unsaturated fatty acids in causing pancreatic organ failure. Characterization of these pathways has led to the identification of potential molecular targets for future therapeutic trials. At the patient level, two classification systems have been developed to classify the severity of acute pancreatitis into prognostically meaningful groups, and several landmark clinical trials have informed management strategies in areas of nutritional support and interventions for infected pancreatic necrosis that have resulted in important changes to acute pancreatitis management paradigms. In this Review, we provide a summary of recent advances in acute pancreatitis with a special emphasis on pathophysiological mechanisms and clinical management of the disorder.
Collapse
|
|
19
|
Coelho AMM, Machado MCC, Sampietre SN, da Silva FP, Cunha JEM, D'Albuquerque LAC. Local and systemic effects of aging on acute pancreatitis. Pancreatology 2019; 19:638-645. [PMID: 31204259 DOI: 10.1016/j.pan.2019.06.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 05/10/2019] [Accepted: 06/08/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND /Objectives: Evaluation of the local and systemic effects of aging on the severity of acute pancreatitis (AP) in an experimental rat model in elderly animals. METHODS AP was induced in Wistar rats by intraductal 2.5% taurocholate injection and divided into two groups: Young (3 month old) and Aged (18 month old). Two and 24 h after AP induction blood samples were collected for determinations of amylase, AST, ALT, urea, creatinine, glucose, and of plasma I-FABP. TNF-α and IL-6 levels were determined in serum and ascitic fluid. Liver mitochondrial function and malondialdehyde (MDA) contents, pancreas histological analysis, and pulmonar myeloperoxidade (MPO) activity were performed. Bacterial translocation was evaluated by bacterial cultures of pancreas. RESULTS A significant increase in serum amylase, AST, ALT, urea, creatinine, glucose, I-FABP, and IL-6 levels, and a reduction in serum and ascitic fluid TNF-α levels were observed in the aged group compared to the young group. Liver mitochondrial dysfunction, MDA contents, and pulmonary MPO activity were increased in the Aged AP group compared to the Young AP group. Positive bacterial cultures obtained from pancreas tissue in aged group were significantly increased compared to the young group. Acinar necrosis was also increased in aged AP group when compared to young AP group. CONCLUSION Aging worsens the course of acute pancreatitis evidenced by increased local and systemic lesions and increased bacterial translocation.
Collapse
Affiliation(s)
| | - Marcel Cerqueira Cesar Machado
- Department of Gastroenterology (LIM/37), Medical School, University of São Paulo, Sao Paulo, Brazil; Department of Clinical Emergency, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
| | - Sandra Nassa Sampietre
- Department of Gastroenterology (LIM/37), Medical School, University of São Paulo, Sao Paulo, Brazil
| | | | | | | |
Collapse
|
|
20
|
Kim MJ, Bae GS, Jo IJ, Choi SB, Kim DG, Jung HJ, Song HJ, Park SJ. Fraxinellone inhibits inflammatory cell infiltration during acute pancreatitis by suppressing inflammasome activation. Int Immunopharmacol 2019; 69:169-177. [PMID: 30716587 DOI: 10.1016/j.intimp.2019.01.043] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 01/04/2019] [Accepted: 01/29/2019] [Indexed: 02/07/2023]
Abstract
Inflammasomes promote the production of pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-18, which are the representative mediators of inflammation. Abnormal activation of inflammasomes leads to the development of inflammatory diseases such as acute pancreatitis (AP). In this study, we demonstrate the inhibitory effects of a new natural compound fraxinellone on inflammasome formation and examine the role of inflammasomes in a mouse model of AP. AP was induced with hourly intraperitoneal injections of supramaximal concentrations of the stable cholecystokinin analogue cerulein (50 μg/kg) for 6 h. Mice were sacrificed 6 h after the final cerulein injection. Blood and pancreas samples were obtained for further experiments. Intraperitoneal injection of fraxinellone significantly inhibited the pancreatic activation of multiple inflammasome molecules such as NACHT, LRR and PYD domains-containing protein 3 (NLRP3), PY-CARD, caspase-1, IL-18, and IL-1β during AP. In addition, fraxinellone treatment inhibited pancreatic injury, elevation in serum amylase and lipase activities, and infiltration of inflammatory cells such as neutrophils and macrophages but had no effect on pancreatic edema. To investigate whether inflammasome activation leads to the infiltration of inflammatory cells, we used parthenolide, a well-known natural inhibitor, and IL-1 receptor antagonist mice. The inhibition of inflammasome activation by pharmacological/or genetic modification restricted the infiltration of inflammatory cells, but not edema, consistent with the results observed with fraxinellone. Taken together, our study highlights fraxinellone as a natural inhibitor of inflammasomes and that inflammasome inhibition may lead to the suppression of inflammatory cells during AP.
Collapse
Affiliation(s)
- Myoung-Jin Kim
- Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea
| | - Gi-Sang Bae
- Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, Jeonbuk 54538, South Korea
| | - Il-Joo Jo
- Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Division of Beauty Sciences, School of Natural sciences, Wonkwang University, Iksan, Jeonbuk 54538, South Korea
| | - Sun-Bok Choi
- Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, Jeonbuk 54538, South Korea
| | - Dong-Goo Kim
- Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, Jeonbuk 54538, South Korea
| | - Hyun-Ju Jung
- Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, South Korea
| | - Ho-Joon Song
- Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea
| | - Sung-Joo Park
- Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, Jeonbuk 54538, South Korea.
| |
Collapse
|
|
21
|
Turkyilmaz S, Cekic AB, Usta A, Alhan E, Kural BV, Ercin C, Sağlam K. Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis. Arch Med Sci 2019; 15:232-239. [PMID: 30697275 PMCID: PMC6348362 DOI: 10.5114/aoms.2017.65231] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Accepted: 09/10/2016] [Indexed: 01/13/2023] Open
Abstract
INTRODUCTION Ethyl pyruvate (EP), a natural flavoring and fragrance agent, has been shown to exert anti-inflammatory and antioxidant actions. We tested the potential beneficial effects of EP in a rat model of acute necrotizing pancreatitis (ANP), a serious condition with a significant inflammatory explosion and oxidative stress. MATERIAL AND METHODS Fifty-two adult male Sprague-Dawley rats were divided into four groups: sham + saline, sham + EP, ANP + saline, and ANP + EP. The ANP was induced by glycodeoxycholic acid and cerulein. Animals were sacrificed at 48 h and biochemical, hematological, and histological markers of ANP and inflammation were assessed. The extent of mortality, systemic cardiorespiratory variables, pancreatic microcirculation, renal/hepatic functions, acinar cell injury and enzyme markers for pancreas and lung tissues were investigated. RESULTS The EP-treated ANP group presented significantly lower mortality than the untreated ANP group (44% (7/16) vs. 19% (3/16), respectively, p < 0.05). Administration of EP resulted in significantly lower levels of IL-6 (ANP + saline: 5470 ±280 vs. ANP + EP: 2250 ±180 pg/ml, p < 0.05). Compared with the ANP group, the ANP + EP group had a lower pancreatic necrosis score (1.45 ±0.2 vs. 0.96 ±0.2, p < 0.05). Moreover, intraperitoneal EP administration had a positive effect on most indices of pancreatitis (amylase and alanine transaminase levels) and lung damage (except lung malondialdehyde levels) as they decreased towards baseline values. CONCLUSIONS The results from this experimental study indicate that EP, a nontoxic chemical approved by the Food and Drug Administration as a food additive, provides positive effects on the course of pancreatitis, suggesting potential usefulness in management of ANP.
Collapse
Affiliation(s)
- Serdar Turkyilmaz
- Department of General Surgery, Karadeniz Technical University, Trabzon, Turkey
| | - Arif Burak Cekic
- Department of General Surgery, Karadeniz Technical University, Trabzon, Turkey
| | - Arif Usta
- Department of General Surgery, Karadeniz Technical University, Trabzon, Turkey
| | - Etem Alhan
- Department of General Surgery, Karadeniz Technical University, Trabzon, Turkey
| | | | - Cengiz Ercin
- Department of Pathology, School of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Kutay Sağlam
- Department of Surgery, Samsun State Hospital, Samsun, Turkey
| |
Collapse
|
|
22
|
Kaphalia BS. Early Biomarkers of Acute and Chronic Pancreatitis. BIOMARKERS IN TOXICOLOGY 2019:341-353. [DOI: 10.1016/b978-0-12-814655-2.00019-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
23
|
Therapeutic effect of ultrasound interventional perirenal catheter-assisted early peripancreatic lavage of protease inhibitor on severe acute pancreatitis in miniature pigs. Pancreatology 2019; 19:158-162. [PMID: 30551934 DOI: 10.1016/j.pan.2018.12.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 11/02/2018] [Accepted: 12/04/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To study the therapeutic effect of early peripancreatic lavage of ulinastatin on severe acute pancreatitis(SAP). METHODS Sixteen pigs were divided into 4 groups: model(SAP), saline lavage(SL), ulinastatin lavage(UL), intravenous ulinastatin(IU). UL and SL group were given peripancreatic lavage of ulinastatin by ultrasound-guided perirenal catheterization and IU group was intravenously instilled with ulinastatin. The multi-organ functions and the inflammatory factors were observed. RESULTS UL group has the best therapeutic effect. The changes of multi-organ functions and the inflammatory factors were compared with SAP group as follows. In time window of treatment: amylase (p < 0.01), lipase (p < 0.01), ALT (p > 0.05), AST (p < 0.05), CR (p < 0.01), UR (p < 0.01), IL-6 (p < 0.01), IL-10 (p < 0.01). In post-treatment phase: amylase (p < 0.01), lipase (p < 0.01), ALT (p < 0.01), AST (p < 0.01), CR (p < 0.05), UR (p > 0.05), IL-6 (p < 0.01), IL-10 (p < 0.01). CONCLUSIONS Early peripancreatic lavage of ulinastatin in SAP could effectively improve the multi-organ functions and inflammatory response.
Collapse
|
|
24
|
Valverde-López F, Wilcox CM, Redondo-Cerezo E. Evaluation and management of acute pancreatitis in Spain. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:618-628. [PMID: 30149943 DOI: 10.1016/j.gastrohep.2018.06.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 06/04/2018] [Accepted: 06/19/2018] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The aim of this systematic review is to summarize epidemiological data and areas of future acute pancreatitis research in Spain. METHODS We conduct an independent search in PubMed and Web of Science and analyse articles by Spanish researchers from 2008 to 2018. RESULTS We identified an overall incidence of 72/100,000 person-years, with biliary pancreatitis as the most common etiology. BISAP was useful but suboptimal for predicting severity and some biomarkers such as Oleic acid chlorohydrin have shown promising results. The modified determinant-based classification can help to classify patients admitted to intensive care units. Ringer's lactate solution is currently the fluid of choice and classic surgery has been surpassed by minimally-invasive approaches. Starting a full-caloric diet is safe when bowel sounds are present. DISCUSSION There are numerous well-defined research fields in Spain. Future multicentre studies should focus on management, predicting severity and cost-effectiveness.
Collapse
Affiliation(s)
- Francisco Valverde-López
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Complejo Hospitalario Universitario de Granada, Granada, Spain.
| | - C Mel Wilcox
- Division of Gastroenterology and Hepatology and Pancreaticobiliary Center, University of Alabama at Birmingham, USA
| | - Eduardo Redondo-Cerezo
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Complejo Hospitalario Universitario de Granada, Granada, Spain
| |
Collapse
|
|
25
|
Abstract
OBJECTIVES The objective of this study is to explore the effect of melatonin on endoplasmic reticulum stress in acute pancreatitis (AP) and the molecular mechanism. METHODS Acute pancreatitis was induced in vivo in Sprague-Dawley rats by the retrograde injection of 5% taurocholate into the biliopancreatic duct and in vitro by treating AR42J cells with cerulein (10 nmol/L) plus lipopolysaccharide (LPS) (10 mg/L). The rats and cells were treated with melatonin (50 mg/kg in rats and 0.5, 1, and 2 mmol/L in AR42J cells) 30 minutes before AP was induced. After 9 hours, the cells and rat pancreas tissue were collected for Western blot, reverse transcription polymerase chain reaction, histological examination, immunohistochemistry, and immunofluorescence analysis. RESULTS Inositol-requiring 1α (IRE1α)-mediated Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) pathway were activated early in AR42J cells and rat AP models. Melatonin significantly inhibited the expression of proinflammatory cytokines. Western blot and immunohistochemical results all indicated that melatonin regulated apoptosis-related protein expression. In addition, melatonin treatment resulted in significantly reduced pancreatic tissue injury, as revealed by histological changes and pathological scores. Furthermore, melatonin treatment significantly reduced the activation of IRE1α-mediated JNK/NF-κB pathway-related proteins. CONCLUSIONS These findings suggest that melatonin protects AR42J cells and Sprague-Dawley rats against AP-associated injury, probably through downregulation of IRE1α-mediated JNK/NF-κB pathways.
Collapse
|
|
26
|
Li Y, Ye Y, Yang M, Ruan H, Yu Y. Application of semi-automated ultrasonography on nutritional support for severe acute pancreatitis. Comput Med Imaging Graph 2018; 67:40-44. [PMID: 29753963 DOI: 10.1016/j.compmedimag.2018.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 03/13/2018] [Accepted: 04/23/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To evaluate the application value of semi-automated ultrasound on the guidance of nasogastrojejunal tube replacement for patients with acute severe pancreatitis (ASP), as well as the value of the nutritional support for standardized treatment in clinical practice. METHODS The retrospective research was performed in our hospital, and 34 patients suffering from ASP were enrolled into this study. All these identified participants ever received CT scans in order to make definitive diagnoses. Following, these patients received semi-automated ultrasound examinations within 1 days after their onset, in order to provide enteral nutrititon treatment via nasogastrojejunal tube, or freehand nasogastrojejunal tube replacement. In terms of statistical analysis, the application value of semi-automated ultrasound guidance on nasogastrojejunal tube replacement was evaluated, and was compared with tube replacement of no guidance. After cathetering, the additional enteral nutrition was provided, and its therapeutic effect on SAP was analyzed in further. RESULTS A total of 34 patients with pancreatitis were identified in this research, 29 cases with necrosis of pancreas parenchyma. After further examinations, 32 cases were SAP, 2 cases were mild acute pancreatitis. When the firm diagnosis was made, additional enteral nutrition (EN) was given, all the patient conditions appeared good, and they all were satisfied with this kind of nutritional support. According to our clinical experience, when there was 200-250 ml liquid in the stomach, the successful rate of intubation appeared higher. Additionally, the comparison between ultrasound-guided and freehand nasogastrojejunal tube replacement was made. According to the statistical results, in terms of the utilization ratio of nutritional support, it was better in ultrasound-guided group, when compared with it in freehand group, within 1 day, after 3 days and after 7 days (7/20 versus 2/14; P < 0.05; 14/20 versus 6/14; P < 0.05; 20/20 versus 12/14; P < 0.05). Besides, the complications caused by cathetering between two groups was not statistically different (P > 0.05). CONCLUSIONS It can be indicated that semi-automated ultrasound guidance is a reliable method for nasogastrojejunal tube replacement, and should be substituted for no guidance of cathetering. In terms of therapeutic effect of EN, additional nutritional support contributed to significantly improve the prognosis of SAP patients, and should be widely recommended in clinical practice. Surely, this conclusion should be evaluated in further, by means of randomized controlled trials and economic evaluation.
Collapse
Affiliation(s)
- Ying Li
- Department of Critical Care Medicine, Second People's Hospital of Shenzhen, Shenzhen, 518035, PR China.
| | - Yu Ye
- Department of Neurosurgery, Longgang Central Hospital of Shenzhen, Shenzhen, 518116, PR China.
| | - Mei Yang
- Department of Critical Care Medicine, Second People's Hospital of Shenzhen, Shenzhen, 518035, PR China.
| | - Haiying Ruan
- Department of Critical Care Medicine, Second People's Hospital of Shenzhen, Shenzhen, 518035, PR China.
| | - Yuan Yu
- Department of Critical Care Medicine, Second People's Hospital of Shenzhen, Shenzhen, 518035, PR China.
| |
Collapse
|
|
27
|
Zhou Y, Zhao L, Mei F, Hong Y, Xia H, Zuo T, Ding Y, Wang W. Macrophage migration inhibitory factor antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy. Mol Med Rep 2018; 17:6576-6584. [PMID: 29512741 PMCID: PMC5928642 DOI: 10.3892/mmr.2018.8672] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 02/14/2018] [Indexed: 12/14/2022] Open
Abstract
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine involved in many acute and chronic inflammatory diseases. However, its role in acute lung injury associated with acute pancreatitis in pregnancy (APIP) has not yet been elucidated. The present study was undertaken to clarify the effect and potential mechanism of MIF antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester (ISO‑1) in the development of acute lung injury in rats with APIP. Eighteen late‑gestation SD rats were randomly assigned to three groups: Sham operation (SO) group, APIP group, and ISO‑1 group. All the rats were sacrificed 6 h after modeling. The severity of pancreatitis was evaluated by serum amylase (AMY), lipase (LIPA), tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 and assessing the histopathological score. Lung injury was determined by performing histology and inflammatory cell infiltration investigations. Western blot analysis was used to detect the protein expression of MIF, phosphorylated and total P38 and nuclear factor‑κB (NF‑κB) protein in lungs. The results showed that MIF was upregulated in the lung of APIP rats. Compared with APIP group, the intervention of ISO‑1 alleviated the pathological injury of the pancreas and lungs, decreased serum AMY and LIPA, attenuated serum concentrations of TNF‑α, IL‑1β, and IL‑6, reduced the number of MPO‑positive cells in the lung and inhibited the activation of P38MAPK and NF‑κB. These results suggest that MIF is activated in lung injury induced by APIP. Furhtermore, the present findings indicate that the MIF antagonist ISO‑1 has a protective effect on lung injury and inflammation, which may be associated with deactivating the P38MAPK and NF‑κB signaling pathway.
Collapse
Affiliation(s)
- Yu Zhou
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Liang Zhao
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Fangchao Mei
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Yupu Hong
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - He Xia
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Teng Zuo
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Youming Ding
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Weixing Wang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| |
Collapse
|
|
28
|
Ren Y, Cui Q, Bi J, Du Z, Zhang J, Zhang X, Lv Y, Wu R. WITHDRAWN: Stilamin inhibits intestinal and pancreatic injury in rats with severe acute pancreatitis by down-regulating LCN2 expression. Pancreatology 2018:S1424-3903(17)30915-8. [PMID: 29325893 DOI: 10.1016/j.pan.2017.12.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 12/23/2017] [Accepted: 12/28/2017] [Indexed: 12/11/2022]
Abstract
This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
Collapse
Affiliation(s)
- Yifan Ren
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Qing Cui
- Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Jianbin Bi
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Zhaoqing Du
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Jia Zhang
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Xufeng Zhang
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Yi Lv
- Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Rongqian Wu
- Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| |
Collapse
|
|
29
|
Abstract
OBJECTIVES Inflammation in the setting of acute pancreatitis (AP) is partially driven by pathogen recognition receptors that recognize damage-associated molecular patterns. Interleukin (IL)-8 is a chemotactic factor produced by pathogen recognition receptor-expressing cells. A single-nucleotide polymorphism in IL8 promoter region (-251 A/T) has been implicated in inflammatory diseases. We examined whether this IL8 polymorphism confers susceptibility to AP. METHODS Patients with AP (n = 357) were prospectively recruited. Clinical data and blood were collected in subjects and controls (n = 347). Severity was defined following the Revised Atlanta Classification. Genotypes were assessed by quantitative polymerase chain reaction using TaqMan probes. RESULTS Patients and controls had similar demographics and had no difference in Hardy-Weinberg (patients, P = 0.29; controls, P = 0.66). Twenty-five percent of patients developed severe AP. Compared with controls, the A/A genotype was more common in AP (P = 0.041; odds ratio, 1.42; 95% confidence interval, 1-1.99). Obese patients with the A/A genotype were more likely to develop mild AP (P = 0.047). CONCLUSIONS The -251 polymorphism confers susceptibility to AP and disease severity in obese patients. However, its effect is moderate. One potential mechanism for this susceptibility is via increased IL8 production by innate cells, with subsequent enhanced neutrophil influx and pancreatic injury.
Collapse
|
|
30
|
Valverde-López F, Matas-Cobos AM, Alegría-Motte C, Jiménez-Rosales R, Úbeda-Muñoz M, Redondo-Cerezo E. BISAP, RANSON, lactate and others biomarkers in prediction of severe acute pancreatitis in a European cohort. J Gastroenterol Hepatol 2017; 32:1649-1656. [PMID: 28207167 DOI: 10.1111/jgh.13763] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Revised: 02/12/2017] [Accepted: 02/14/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The study aims to assess and compare the predicting ability of some scores and biomarkers in acute pancreatitis. METHODS We prospectively collected data from 269 patients diagnosed of acute pancreatitis, admitted to Virgen de las Nieves University Hospital between June 2010 and June 2012. Blood urea nitrogen (BUN), C-reactive protein, and creatinine were measured on admission and after 48 h, lactate and bedside index for severity acute pancreatitis (BISAP) only on admission and RANSON within the first 48 h. Definitions from 2012 Atlanta Classification were used. Area under the curve (AUC) was calculated for each scoring system for predicting severe acute pancreatitis (SAP), mortality, and intensive care unit (ICU) admission, obtaining optimal cut-off values from the receiver operating characteristic curves. RESULTS Eight (3%) patients died, 17 (6.3%) were classified as SAP, and 10 (3.7%) were admitted in ICU. BISAP was the best predictor on admission for SAP, mortality, and ICU admission with an AUC of 0.9 (95% CI 0.83-0.97); 0.97 (95% CI 0.95-0.99); and 0.89 (95% CI 0.79-0.99), respectively. After 48 h, BUN 48 h was the best predictor of SAP (AUC = 0.96 CI: 0.92-0.99); BUN 48 h and BISAP were the best predictors for mortality (AUC = 0.97 CI: 0.95-0.99) and creatinine 48 h for ICU admission (AUC = 0.96 CI: 0.92-0.99). Lactate showed an AUC of 0.79 (CI: 0.71-0.88), 0.87 (CI: 0.78-0.96), and 0.77 (CI: 0.67-0.87) for SAP, mortality, and ICU admission, respectively. All parameters were predictors for SAP, mortality, and ICU admission, but C-reactive protein on admission was only a significant predictor of SAP. CONCLUSION Bedside index for severity acute pancreatitis is a good predictive system for SAP, mortality, and ICU admission, being useful for triaging patients for ICU management. Lactate could be useful for developing new scores.
Collapse
Affiliation(s)
- Francisco Valverde-López
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - Ana M Matas-Cobos
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - Carlos Alegría-Motte
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - Rita Jiménez-Rosales
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - Margarita Úbeda-Muñoz
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - Eduardo Redondo-Cerezo
- Department of Gastroenterology and Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| |
Collapse
|
|
31
|
Bonior J, Warzecha Z, Ceranowicz P, Gajdosz R, Pierzchalski P, Kot M, Leja-Szpak A, Nawrot-Porąbka K, Link-Lenczowski P, Pędziwiatr M, Olszanecki R, Bartuś K, Trąbka R, Kuśnierz-Cabala B, Dembiński A, Jaworek J. Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats. Int J Mol Sci 2017; 18:E1402. [PMID: 28665321 PMCID: PMC5535895 DOI: 10.3390/ijms18071402] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Revised: 06/25/2017] [Accepted: 06/27/2017] [Indexed: 12/11/2022] Open
Abstract
Ghrelin was shown to exhibit protective and therapeutic effect in the gut. Aim of the study was to investigate the role of sensory nerves (SN) in the protective effect of ghrelin in acute pancreatitis (AP). Studies were performed on male Wistar rats or isolated pancreatic acinar cells. After capsaicin deactivation of sensory nerves (CDSN) or treatment with saline, rats were pretreated intraperitoneally with ghrelin or saline. In those rats, AP was induced by cerulein or pancreases were used for isolation of pancreatic acinar cells. Pancreatic acinar cells were incubated in cerulein-free or cerulein containing solution. In rats with intact SN, pretreatment with ghrelin led to a reversal of the cerulein-induced increase in pancreatic weight, plasma activity of lipase and plasma concentration of tumor necrosis factor-α (TNF-α). These effects were associated with an increase in plasma interleukin-4 concentration and reduction in histological signs of pancreatic damage. CDSN tended to increase the severity of AP and abolished the protective effect of ghrelin. Exposure of pancreatic acinar cells to cerulein led to increase in cellular expression of mRNA for TNF-α and cellular synthesis of this cytokine. Pretreatment with ghrelin reduced this alteration, but this effect was only observed in acinar cells obtained from rats with intact SN. Moreover, CDSN inhibited the cerulein- and ghrelin-induced increase in gene expression and synthesis of heat shock protein 70 (HSP70) in those cells. Ghrelin exhibits the protective effect in cerulein-induced AP on the organ and pancreatic acinar cell level. Sensory nerves ablation abolishes this effect.
Collapse
Affiliation(s)
- Joanna Bonior
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| | - Zygmunt Warzecha
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegórzecka St., 31-531 Krakow, Poland.
| | - Piotr Ceranowicz
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegórzecka St., 31-531 Krakow, Poland.
| | - Ryszard Gajdosz
- Department of Emergency Medical Care, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| | - Piotr Pierzchalski
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| | - Michalina Kot
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| | - Anna Leja-Szpak
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| | - Katarzyna Nawrot-Porąbka
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| | - Paweł Link-Lenczowski
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| | - Michał Pędziwiatr
- 2nd Department of Surgery, Faculty of Medicine, Jagiellonian University Medical College, 21 Kopernika St., 31-501 Krakow, Poland.
| | - Rafał Olszanecki
- Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegórzecka St., 31-531 Krakow, Poland.
| | - Krzysztof Bartuś
- Department of Cardiovascular Surgery and Transplantology, Faculty of Medicine, Jagiellonian University, JP II Hospital, 80 Prądnicka St., 31-202 Krakow, Poland.
| | - Rafał Trąbka
- Department of Rehabilitation, Faculty of Health Sciences, Jagiellonian University Medical College, 3 Koło Strzelnicy St., 30-219 Krakow, Poland.
| | - Beata Kuśnierz-Cabala
- Department of Diagnostics, Chair of Clinical Biochemistry, Faculty of Medicine Jagiellonian University Medical College, 15 A Kopernika St., 31-501 Krakow, Poland.
| | - Artur Dembiński
- Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegórzecka St., 31-531 Krakow, Poland.
| | - Jolanta Jaworek
- Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 12 Michałowskiego St., 31-126 Krakow, Poland.
| |
Collapse
|
|
32
|
Immature granulocytes predict severe acute pancreatitis independently of systemic inflammatory response syndrome. GASTROENTEROLOGY REVIEW 2017; 12:140-144. [PMID: 28702104 PMCID: PMC5497134 DOI: 10.5114/pg.2017.68116] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 03/28/2017] [Indexed: 12/29/2022]
Abstract
Introduction Early prediction of severity of acute pancreatitis (AP) by a simple parameter that positively correlates with the activation stage of the immune system would be very helpful because it could influence the management and improve the outcome. Tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) play a critical role in the pathogenesis systemic inflammatory response syndrome (SIRS) and severity of AP. One of the effects of IL-1 and TNF-α is an increase in the number of immature granulocytes (IGs) in the peripheral blood. Aim To assess whether the IGs% in plasma could be an independent marker of AP severity. Material and methods A cohort of 77 patients with AP were prospectively enrolled in the study. The IGs were measured from whole blood samples obtained from the first day of hospitalization using an automated analyser. Results We observed 44 (57%) patients with mild AP, 21 (27%) patients with moderate severe AP (SAP) and 12 (16%) patients with SAP. The cut-off value of IGs was 0.6%. The IGs > 0.6% had a sensitivity, specificity, and positive and negative predictive value of 100%, 96%, 85.7%, and 100%, respectively (area under the curve (AUC) = 0.98). On admission, SIRS was present in 25 (32%) patients. We found that in patients who fulfilled at least two criteria for SIRS, SAP could be predicted with 75% sensitivity and 75.4% specificity, positive predictive value 36%, negative predictive value 94.2%. Conclusions The IGs% as a routinely obtained marker appears to be a promising, independent biomarker and a better predictor of early prognosis in SAP than SIRS and white blood cell.
Collapse
|
|
33
|
Abstract
BACKGROUND Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology. DATA SOURCES Studies published between 1st January 1991 and 31st December 2015 were identified with PubMed, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings: "acute pancreatitis, necrosis, mortality, pathogenesis, incidence" and the terms "open necrosectomy and minimally invasive necrosectomy". The National Institute of Clinical Excellence (NICE) Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks. RESULTS The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology, acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed. The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach. CONCLUSIONS Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the latest UK guidelines for management of severe acute pancreatitis.
Collapse
|
|
34
|
Choi SB, Bae GS, Jo IJ, Wang S, Song HJ, Park SJ. Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways. Mol Immunol 2016; 74:27-38. [PMID: 27148818 DOI: 10.1016/j.molimm.2016.04.011] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 04/19/2016] [Accepted: 04/26/2016] [Indexed: 01/14/2023]
Abstract
Acute pancreatitis (AP) is a life-threatening disease. Berberine (BBR), a well-known plant alkaloid, is reported to have anti-inflammatory activity in many diseases. However, the effects of BBR on AP have not been clearly elucidated. Therefore, the present study aimed to investigate the effects of BBR on cerulein-induced AP in mice. AP was induced by either cerulein or l-arginine. In the BBR treated group, BBR was administered intraperitoneally 1h before the first cerulein or l-arginine injection. Blood samples were obtained to determine serum amylase and lipase activities and nitric oxide production. The pancreas and lung were rapidly removed for examination of histologic changes, myeloperoxidase (MPO) activity, and real-time reverse transcription-polymerase chain reaction. Furthermore, the regulating mechanisms of BBR were evaluated. Treatment of mice with BBR reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury, as well as inhibited several inflammatory parameters such as the expression of pro-inflammatory cytokines and inducible nitric oxide synthesis (iNOS). Furthermore, BBR administration significantly inhibited c-Jun N-terminal kinase (JNK) activation in the cerulein-induced AP. Deactivation of JNK resulted in amelioration of pancreatitis and the inhibition of inflammatory mediators. These results suggest that BBR exerts anti-inflammatory effects on AP via JNK deactivation on mild and severe acute pancreatitis model, and could be a beneficial target in the management of AP.
Collapse
Affiliation(s)
- Sun-Bok Choi
- BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea; Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea
| | - Gi-Sang Bae
- Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea; Hanbang Body Fluid Research Center, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea
| | - Il-Joo Jo
- Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea; Hanbang Body Fluid Research Center, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea
| | - Shaofan Wang
- School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China
| | - Ho-Joon Song
- BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea; Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea
| | - Sung-Joo Park
- BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea; Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea; Hanbang Body Fluid Research Center, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea.
| |
Collapse
|
|
35
|
Xiang H, Zhang Q, Wang D, Xia S, Wang G, Zhang G, Chen H, Wu Y, Shang D. iTRAQ-based quantitative proteomic analysis for identification of biomarkers associated with emodin against severe acute pancreatitis in rats. RSC Adv 2016; 6:72447-72457. [DOI: 10.1039/c6ra16446c] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/30/2023] Open
Abstract
Emodin has potent actions against SAP injury by inhibiting the HTRA1/TGF-β1 signaling pathway and subsequent inflammatory responses.
Collapse
Affiliation(s)
- Hong Xiang
- College (Institute) of Integrative Medicine
- Dalian Medical University
- Dalian 116011
- China
- Institute of Gene Engineered Animal Models for Human Diseases
| | - Qingkai Zhang
- Department of General Surgery
- Pancreatico-Biliary Center
- The First Affiliated Hospital of Dalian Medical University
- Dalian 116011
- China
| | - Danqi Wang
- Clinical Laboratory of Integrative Medicine
- The First Affiliated Hospital of Dalian Medical University
- Dalian 116011
- China
| | - Shilin Xia
- Clinical Laboratory of Integrative Medicine
- The First Affiliated Hospital of Dalian Medical University
- Dalian 116011
- China
| | - Guijun Wang
- Department of General Surgery
- The First Affiliated Hospital of Jinzhou Medical University
- Jinzhou 121000
- China
| | - Guixin Zhang
- Department of General Surgery
- Pancreatico-Biliary Center
- The First Affiliated Hospital of Dalian Medical University
- Dalian 116011
- China
| | - Hailong Chen
- Department of General Surgery
- Pancreatico-Biliary Center
- The First Affiliated Hospital of Dalian Medical University
- Dalian 116011
- China
| | - Yingjie Wu
- College (Institute) of Integrative Medicine
- Dalian Medical University
- Dalian 116011
- China
- Institute of Gene Engineered Animal Models for Human Diseases
| | - Dong Shang
- College (Institute) of Integrative Medicine
- Dalian Medical University
- Dalian 116011
- China
- Department of General Surgery
| |
Collapse
|
|
36
|
Yang YX, Li L. Evaluating the Ability of the Bedside Index for Severity of Acute Pancreatitis Score to Predict Severe Acute Pancreatitis: A Meta-Analysis. Med Princ Pract 2016; 25:137-42. [PMID: 26613249 PMCID: PMC5588330 DOI: 10.1159/000441003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Accepted: 09/10/2015] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To evaluate the diagnostic performance of the bedside index for severity in acute pancreatitis (BISAP) score in predicting severe acute pancreatitis (SAP). MATERIALS AND METHODS A systematic search was conducted using PubMed, Cochrane library and EMBASE databases up to May 2014, and 9 related studies, including 1,972 subjects, were reviewed. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnosis of odds ratio (DOR) and hierarchic summary receiver-operating characteristic (HSROC) curves, as well as the area under the HSROC curve (AUC), were assessed using the HSROC and bivariate mixed effects models. Moreover, a subgroup analysis stratified by cutoff value was performed to measure the effect of the diagnostic threshold on the performance of the BISAP score. Finally, publication bias was assessed using Deeks' funnel plot asymmetry test. Statistical analyses were performed using the STATA 12.0 software. RESULTS The pooled sensitivity, specificity, PLR, NLR and DOR of the BISAP for predicting SAP were 64.82% (95% CI: 54.47-73.74%), 83.62% (95% CI: 70.03-91.77%), 3.96 (95% CI: 2.27-6.89), 0.42 (95% CI: 0.34-0.52) and 9.41 (95% CI: 5.38-16.45), respectively. The AUC was 0.77 (95% CI: 0.73-0.80). Moreover, the subgroup analysis results demonstrated that the BISAP cutoff point at 3 had a higher specificity and greater accuracy than at 2 to predict SAP. No significant publication bias was detected across the studies (p = 0.359). CONCLUSION The BISAP score showed low sensitivity but high specificity for assessing the severity of acute pancreatitis.
Collapse
Affiliation(s)
| | - Li Li
- *Li Li, MD, Department of Emergency Medicine, The First Affiliated Hospital of Zhenzhou University, Jianshe Donglu, No. 1, Zhengzhou 450052, Henan (China), E-Mail
| |
Collapse
|
|
37
|
Feng C, Li B, Wang LL, Chen LI, Zhou X, Lv FQ, Li TS. Effect of peritoneal lavage with ulinastatin on the expression of NF-κB and TNF-α in multiple organs of rats with severe acute pancreatitis. Exp Ther Med 2015; 10:2029-2034. [PMID: 26668591 PMCID: PMC4665968 DOI: 10.3892/etm.2015.2802] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2014] [Accepted: 06/22/2015] [Indexed: 01/15/2023] Open
Abstract
The aim of the present study was to investigate the effect of peritoneal lavage with ulinastatin on the expression levels of nuclear factor κB (NF-κB) and tumor necrosis factor (TNF)-α in multiple organs of rats with severe acute pancreatitis (SAP). Male Wistar rats were randomly divided into the following groups: Sham-operated (C), SAP model (SAP), saline lavage (SL), intravenous ulinastatin (IU) and peritoneal lavage with ulinastatin (UL). The SAP model was induced by the retrograde infusion of 5% sodium taurocholate into the biliopancreatic ducts of the rats. Intraperitoneal lavage or injection was performed immediately following the establishment of the SAP model in groups SL, IU and UL. Intraperitoneal lavage with or without ulinastatin was performed for 3 h. The survival time of half of the rats in each group was recorded over a 12-h period. At 3 h after the induction of SAP, inflammatory mediators and the expression levels of NF-κB and TNF-α in multiple organs of the rats in each group were also detected. The survival rates of the rats in group UL at 6 h and 9 h were increased compared with those in group SAP, and were also higher than that in groups SL and IU. The levels of serum inflammatory mediators were effectively reduced in groups SL, IU and UL, the greatest effects were observed in group UL. The expression levels of NF-κB and TNF-α in multiple organs were significantly lower in group UL compared with other groups. Intraperitoneal lavage with ulinastatin significantly ameliorated the inflammatory reaction and inhibited NF-κB and TNF-α expression in multiple organs of SAP model rats.
Collapse
Affiliation(s)
- Cong Feng
- Department of Emergency, PLA General Hospital, Beijing 100853, P.R. China ; Li-Shi Road Outpatient Department, Second Artillery General Hospital of the PLA, Beijing 100820, P.R. China
| | - Bei Li
- Department of Emergency, PLA General Hospital, Beijing 100853, P.R. China
| | - Li-Li Wang
- Department of Emergency, PLA General Hospital, Beijing 100853, P.R. China
| | - L I Chen
- Department of Emergency, PLA General Hospital, Beijing 100853, P.R. China
| | - Xuan Zhou
- Department of Emergency, PLA General Hospital, Beijing 100853, P.R. China
| | - Fa-Qin Lv
- Department of Ultrasound, PLA General Hospital, Beijing 100853, P.R. China
| | - Tan-Shi Li
- Department of Emergency, PLA General Hospital, Beijing 100853, P.R. China
| |
Collapse
|
|
38
|
Nawaz H, Koutroumpakis E, Easler J, Slivka A, Whitcomb DC, Singh VP, Yadav D, Papachristou GI. Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis. Am J Gastroenterol 2015; 110:1497-503. [PMID: 26323188 DOI: 10.1038/ajg.2015.261] [Citation(s) in RCA: 186] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Accepted: 07/05/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Hypertriglyceridemia (HTG) represents a major health problem with prevalence exceeding 30% in the U.S. The present study aims to assess the effect of elevated serum triglyceride (TG) levels on the severity of acute pancreatitis (AP). METHODS Prospectively enrolled AP patients were categorized into normal, mild, moderate, and severe/very severe categories based on their TG levels and compared in respect to demographics, comorbidities, and clinical outcomes. Multivariate analysis determined whether elevated TG levels were independently associated with persistent organ failure. RESULTS Two hundred and one out of 400 AP patients had serum TGs measured within 72 h of presentation, of which 115 had normal TG levels and 86 HTG (20 mild, 41 moderate, and 25 severe/very severe). Patients with HTG were of younger age (44 vs. 52 years), predominantly male (65% vs. 45%), obese (57% vs. 34%), diabetic (38% vs. 17%), and developed more frequently persistent organ failure (40% vs. 17%) compared with those with normal TGs (P<0.02). The rate of persistent organ failure increased proportionally with HTG severity grades (17% when normal TGs, 30% in mild, 39% in moderate, and 48% in severe/very severe HTG, Ptrend<0.001). On multivariate analysis controlling for age, gender, body mass index, diabetes, and alcohol etiology, moderate HTG (odds ratio (OR), 2.6; P=0.04) and severe/very severe HTG (OR, 4.9; P=0.009) were independently associated with persistent organ failure. CONCLUSIONS Elevated serum TGs in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology. TG-mediated lipotoxicity may be an attractive target to design novel interventions for severe AP.
Collapse
Affiliation(s)
- Haq Nawaz
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Efstratios Koutroumpakis
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Jeffrey Easler
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Adam Slivka
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - David C Whitcomb
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Vijay P Singh
- Department of Medicine, Division of Gastroenterology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Dhiraj Yadav
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Georgios I Papachristou
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.,Division of Gastroenterology, Department of Medicine, Veterans Affairs Pittsburgh Health System, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
39
|
Kim MJ, Bae GS, Choi SB, Jo IJ, Kim DG, Shin JY, Lee SK, Kim MJ, Song HJ, Park SJ. Lupeol Protects Against Cerulein-Induced Acute Pancreatitis in Mice. Phytother Res 2015; 29:1634-9. [DOI: 10.1002/ptr.5423] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 07/01/2015] [Accepted: 07/01/2015] [Indexed: 01/26/2023]
Affiliation(s)
- Min-Jun Kim
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Gi-Sang Bae
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- Hanbang Body-Fluid Research Center; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Sun Bok Choi
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Il-Joo Jo
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Dong-Goo Kim
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Joon-Yeon Shin
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Sung-Kon Lee
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Myoung-Jin Kim
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Ho-Joon Song
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| | - Sung-Joo Park
- Department of Herbology, School of Oriental Medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- BK21 Plus Team, Professional Graduate School of Oriental medicine; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
- Hanbang Body-Fluid Research Center; Wonkwang University; Iksan Jeonbuk 540-749 Republic of Korea
| |
Collapse
|
|
40
|
Ferreira ADF, Bartelega JA, Urbano HCDA, de Souza IKF. Acute pancreatitis gravity predictive factors: which and when to use them? ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2015; 28:207-11. [PMID: 26537149 PMCID: PMC4737365 DOI: 10.1590/s0102-67202015000300016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 01/08/2015] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Acute pancreatitis has as its main causes lithiasic biliary disease and alcohol abuse. Most of the time, the disease shows a self-limiting course, with a rapid recovery, only with supportive treatment. However, in a significant percentage of cases, it runs with important local and systemic complications associated with high mortality rates. AIM To present the current state of the use of these prognostic factors (predictive scores) of gravity, as the time of application, complexity and specificity. METHOD A non-systematic literature review through 28 papers, with emphasis on 13 articles published in indexed journals between 2008 and 2013 using Lilacs, Medline, Pubmed. RESULTS Several clinical, laboratory analysis, molecular and image variables can predict the development of severe acute pancreatitis. Some of them by themselves can be determinant to the progression of the disease to a more severe form, such as obesity, hematocrit, age and smoking. Hematocrit with a value lower than 44% and serum urea lower than 20 mg/dl, both at admission, appear as risk factors for pancreatic necrosis. But the PCR differentiates mild cases of serious ones in the first 24 h. Multifactorial scores measured on admission and during the first 48 h of hospitalization have been used in intensive care units, being the most ones used: Ranson, Apache II, Glasgow, Iget and Saps II. CONCLUSION Acute pancreatitis is a disease in which several prognostic factors are employed being useful in predicting mortality and on the development of the severe form. It is suggested that the association of a multifactorial score, especially the Saps II associated with Iget, may increase the prognosis accuracy. However, the professional's preferences, the experience on the service as well as the available tools, are factors that have determined the choice of the most suitable predictive score.
Collapse
|
|
41
|
Malik AM. Acute pancreatitis. A more common and severe complication of gallstones in males. Int J Health Sci (Qassim) 2015; 9:141-5. [PMID: 26309432 PMCID: PMC4538890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023] Open
Abstract
OBJECTIVE To describe an increased incidence and severity of gallstone pancreatitis in males compared to females. DESIGN METHODS This is a retrospective observational comparative study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, over 3 years from June 2008 to June 2011. The study includes two hundred and thirty seven (237) patients with a mean age of 52.38, Std 13.311,65 (22-87) with 157 (66.24%) females and 80 (33.75%) males who were admitted as acute abdominal pain secondary to gallstones. The patients were mostly diagnosed on ultrasonography and enzyme studies. Demographics and other variables are studied and statistical analysis done on SPSS version 20. RESULTS More frequent cases of severe acute pancreatitis were observed in males with gallstones (70%) compared to females (P<0.001). The aged people had a high prevalence while males were more likely to develop local and systemic complications. Severity stratification was done based on different criteria's like Ranson's criteria, and APACHEII. Overall mortality was 7.59%. Mortality among males was significantly high (70%, n=16) in our study due to an increased incidence of fulminant course of the disease. CONCLUSION Contrary to the belief, gallstone associated acute pancreatitis is getting more common in our society and especially so in male population.
Collapse
Affiliation(s)
- Arshad M. Malik
- Associate Professor, Department of Surgery, College of Medicine, Qassim University, KSA
| |
Collapse
|
|
42
|
Determination of iNOS-2087A>G Polymorphism in Acute Pancreatitis Patients. CURRENT HEALTH SCIENCES JOURNAL 2014; 40:249-52. [PMID: 26793321 PMCID: PMC4709709 DOI: 10.12865/chsj.40.04.03] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Accepted: 10/15/2014] [Indexed: 12/22/2022]
Abstract
PURPOSE To determine whether single nucleotide polymorphism (SNP) of inducible nitric oxide synthase (iNOS) is involved in susceptibility for acute pancreatitis. MATERIAL AND METHODS Genomic DNA was extracted from blood samples collected from cases of acute pancreatitis (n=110) and normal population controls frequency matched for age and sex (n=232). iNOS - 2087A>G polymorphism was genotyped using TaqMan allelic discrimination assays. The association of the genetic polymorphism with clinical and pathological data of the patients was evaluated. RESULTS We have found no significant statistical association between this polymorphism and an increased risk of developing acute pancreatitis. CONCLUSION In Romanian population, the risk of developing acute pancreatitis is not increased by the presence of iNOS-2087A>G polymorphism.
Collapse
|
|
43
|
Zhang XH, Li ML, Wang B, Guo MX, Zhu RM. Caspase-1 inhibition alleviates acute renal injury in rats with severe acute pancreatitis. World J Gastroenterol 2014; 20:10457-10463. [PMID: 25132762 PMCID: PMC4130853 DOI: 10.3748/wjg.v20.i30.10457] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 11/04/2013] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis (SAP).
METHODS: Forty-two Sprague-Dawley rats were randomly divided into three groups: healthy controls (HC, n = 6), SAP rats treated with saline (SAP-S, n = 18), or SAP rats treated with a caspase-1/interleukin (IL)-1β-converting-enzyme (ICE) inhibitor (SAP-I-ICE, n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats were subjected to identical treatment and surgical procedures without sodium taurocholate. Rats received an intraperitoneal injection of isotonic saline (SAP-S) or the inhibitor (SAP-ICE-I) at 2 and 12 h after induction of acute pancreatitis. Surviving rats were sacrificed at different time points after SAP induction; all samples were obtained and stored for subsequent analyses. The levels of blood urea nitrogen (BUN) and creatinine (Cr) were measured using automatic methods, and serum IL-1β concentrations were measured by an enzyme-linked immunosorbent assay. Intrarenal expression of IL-1β, IL-18 and caspase-1 mRNAs was detected by RT-PCR. IL-1β protein expression and the pathologic changes in kidney tissues were observed by microscopy after immunohistochemical or hematoxylin and eosin staining, respectively.
RESULTS: The serum levels of BUN and Cr in the SAP-S group were 12.48 ± 2.30 mmol/L and 82.83 ± 13.89 μmol/L at 6 h, 23.53 ± 2.58 mmol/L and 123.67 ± 17.67 μmol/L at 12 h, and 23.60 ± 3.33 mmol/L and 125.33 ± 21.09 μmol/L at 18 h, respectively. All were significantly increased compared to HC rats (P < 0.01 for all). Levels in SAP-ICE-I rats were significantly decreased compared to SAP-S rats both at 12 and 18 h (P < 0.01 for all). Serum IL-1β levels in the SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h; all significantly higher than those in the HC and SAP-ICE-I groups (P < 0.01 for all). Intrarenal expression of IL-1β mRNA was weak in HC rats, but increased significantly in SAP-S rats (P < 0.01). ICE inhibition significantly decreased the expression of IL-1β and IL-18 mRNAs (P < 0.05 for all vs SAP-S), whereas caspase-1 mRNA expression was not significantly different. Weak IL-1β immunostaining was observed in HC animals, and marked staining was found in the SAP-S group mainly in renal tubular epithelial cells. IL-1β immunostaining was significantly descended in SAP-ICE-I rats compared to SAP-S rats (P < 0.05). Caspase-1 inhibition had no effect on the severity of kidney tissue destruction.
CONCLUSION: The expression of caspase-1-activated cytokines IL-1β and IL-18 plays a pivotal role in acute renal injury in rats with experimental SAP. Caspase-1 inhibition improves renal function effectively.
Collapse
|
|
44
|
Wu L, Cai B, Zheng S, Liu X, Cai H, Li H. Effect of emodin on endoplasmic reticulum stress in rats with severe acute pancreatitis. Inflammation 2014; 36:1020-9. [PMID: 23605470 DOI: 10.1007/s10753-013-9634-y] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This study aimed to investigate the protective effect of emodin on endoplasmic reticulum (ER) stress in rats with severe acute pancreatitis (SAP) and the underlying molecular mechanism. Sprague-Dawley male rats were randomly divided into sham operation group, SAP model group, and emodin treatment group. SAP was constructed through injecting sodium taurocholate into pancreatic and biliary duct in rats. Half an hour before establishing the animal model, emodin or sodium carboxymethylcellulose was intragastrically administrated to the rats in respective group. Rats were killed at 3, 6, and 12 h postdisease induction. The amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in serum, pancreatic histopathology, acinar ER ultrastructure, protein expression of Bip, IRE1α,TRAF2, ASK1, p-JNK, and p-p38 MAPK in pancreas were examined. Sodium taurocholate induced pancreatic injury and ER lumen dilated in exocrine pancreas in rats at 3-, 6-, and 12-h time points. ER stress transducers Bip, IRE1α, and their downstream molecules TRAF2, ASK1 in pancreatitis were upregulated. Furthermore, phosphorylation of JNK and p38MAPK in pancreas was increased, which induced high expression level of inflammatory cytokines such as TNF-α and IL-6. Treatment with emodin obviously ameliorated pancreatic injury and decreased the release of amylase and inflammatory cytokines. Further studies showed that emodin significantly decreased the expression of Bip, IRE1α, TRAF2, and ASK1, inhibited phosphorylation of JNK and p38 MAPK in pancreas in rats at all time points. Emodin could reduce pancreatic injury and restrain inflammatory reaction in SAP rats partly via inhibiting ER stress transducers IRE1α and its downstream molecules.
Collapse
Affiliation(s)
- Li Wu
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China
| | | | | | | | | | | |
Collapse
|
|
45
|
Wang YZ, Zhang YC, Cheng JS, Ni Q, Li PW, Han W, Zhang YL. Protective Effects of BML-111 on Cerulein-Induced Acute Pancreatitis-Associated Lung Injury via Activation of Nrf2/ARE Signaling Pathway. Inflammation 2014; 37:1120-33. [DOI: 10.1007/s10753-014-9836-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
46
|
Lesina M, Wörmann SM, Neuhöfer P, Song L, Algül H. Interleukin-6 in inflammatory and malignant diseases of the pancreas. Semin Immunol 2014; 26:80-7. [DOI: 10.1016/j.smim.2014.01.002] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 01/06/2014] [Indexed: 02/07/2023]
|
|
47
|
|
|
48
|
da Costa DW, Boerma D, van Santvoort HC, Horvath KD, Werner J, Carter CR, Bollen TL, Gooszen HG, Besselink MG, Bakker OJ. Staged multidisciplinary step-up management for necrotizing pancreatitis. Br J Surg 2013; 101:e65-79. [DOI: 10.1002/bjs.9346] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2013] [Indexed: 12/16/2022]
Abstract
Abstract
Background
Some 15 per cent of all patients with acute pancreatitis develop necrotizing pancreatitis, with potentially significant consequences for both patients and healthcare services.
Methods
This review summarizes the latest insights into the surgical and medical management of necrotizing pancreatitis. General management strategies for the treatment of complications are discussed in relation to the stage of the disease.
Results
Frequent clinical evaluation of the patient's condition remains paramount in the first 24–72 h of the disease. Liberal goal-directed fluid resuscitation and early enteral nutrition should be provided. Urgent endoscopic retrograde cholangiopancreatography is indicated when cholangitis is suspected, but it is unclear whether this is appropriate in patients with predicted severe biliary pancreatitis without cholangitis. Antibiotic prophylaxis does not prevent infection of necrosis and antibiotics are not indicated as part of initial management. Bacteriologically confirmed infections should receive targeted antibiotics. With the more conservative approach to necrotizing pancreatitis currently advocated, fine-needle aspiration culture of pancreatic or extrapancreatic necrosis will less often lead to a change in management and is therefore indicated less frequently. Optimal treatment of infected necrotizing pancreatitis consists of a staged multidisciplinary ‘step-up’ approach. The initial step is drainage, either percutaneous or transluminal, followed by surgical or endoscopic transluminal debridement only if needed. Debridement is delayed until the acute necrotic collection has become ‘walled-off’.
Conclusion
Outcome following necrotizing pancreatitis has improved substantially in recent years as a result of a shift from early surgical debridement to a staged, minimally invasive, multidisciplinary, step-up approach.
Collapse
Affiliation(s)
- D W da Costa
- Department of Operating Theatres and Evidence Based Surgery, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands
| | - D Boerma
- Department of Surgery, St Antonius Hospital, Nieuwegein, The Netherlands
| | - H C van Santvoort
- Department of Surgery, St Antonius Hospital, Nieuwegein, The Netherlands
| | - K D Horvath
- Department of Surgery, University of Washington Medical Center, Seattle, Washington, USA
| | - J Werner
- Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - C R Carter
- Department of Surgery, Glasgow Royal Infirmary, Glasgow, UK
| | - T L Bollen
- Department of Radiology, St Antonius Hospital, Nieuwegein, The Netherlands
| | - H G Gooszen
- Department of Operating Theatres and Evidence Based Surgery, Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands
| | - M G Besselink
- Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands
| | - O J Bakker
- Department of Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
| |
Collapse
|
|
49
|
Zhang H, Neuhöfer P, Song L, Rabe B, Lesina M, Kurkowski MU, Treiber M, Wartmann T, Regnér S, Thorlacius H, Saur D, Weirich G, Yoshimura A, Halangk W, Mizgerd JP, Schmid RM, Rose-John S, Algül H. IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality. J Clin Invest 2013; 123:1019-1031. [PMID: 23426178 PMCID: PMC3582130 DOI: 10.1172/jci64931] [Citation(s) in RCA: 223] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Accepted: 12/17/2012] [Indexed: 02/06/2023] Open
Abstract
Acute lung injury (ALI) is an inflammatory disease with a high mortality rate. Although typically seen in individuals with sepsis, ALI is also a major complication in severe acute pancreatitis (SAP). The pathophysiology of SAP-associated ALI is poorly understood, but elevated serum levels of IL-6 is a reliable marker for disease severity. Here, we used a mouse model of acute pancreatitis-associated (AP-associated) ALI to determine the role of IL-6 in ALI lethality. Il6-deficient mice had a lower death rate compared with wild-type mice with AP, while mice injected with IL-6 were more likely to develop lethal ALI. We found that inflammation-associated NF-κB induced myeloid cell secretion of IL-6, and the effects of secreted IL-6 were mediated by complexation with soluble IL-6 receptor, a process known as trans-signaling. IL-6 trans-signaling stimulated phosphorylation of STAT3 and production of the neutrophil attractant CXCL1 in pancreatic acinar cells. Examination of human samples revealed expression of IL-6 in combination with soluble IL-6 receptor was a reliable predictor of ALI in SAP. These results demonstrate that IL-6 trans-signaling is an essential mediator of ALI in SAP across species and suggest that therapeutic inhibition of IL-6 may prevent SAP-associated ALI.
Collapse
Affiliation(s)
- Hong Zhang
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Patrick Neuhöfer
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Liang Song
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Björn Rabe
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Marina Lesina
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Magdalena U. Kurkowski
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Matthias Treiber
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Thomas Wartmann
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Sara Regnér
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Henrik Thorlacius
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Dieter Saur
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Gregor Weirich
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Akihiko Yoshimura
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Walter Halangk
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Joseph P. Mizgerd
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Roland M. Schmid
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Stefan Rose-John
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Hana Algül
- II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Institute of Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Department of Surgery, Division of Experimental Surgery, Otto-von-Guericke University, Magdeburg, Germany.
Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, Malmö, Sweden.
Pathologisches Institut, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Department of Microbiology and Immunology, Keio University School of Tokyo, and Japan Science and Technology Agency (JST), CREST, Chiyoda-ku, Tokyo, Japan.
Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| |
Collapse
|
|
50
|
Easler JJ, Zureikat A, Papachristou GI. An update on minimally invasive therapies for pancreatic necrosis. Expert Rev Gastroenterol Hepatol 2012; 6:745-53. [PMID: 23237259 DOI: 10.1586/egh.12.48] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Pancreatic necrosis is a local complication of severe acute pancreatitis associated with multiple organ dysfunction, infection and increased mortality. While surgery is the mainstay for invasive management, studies have demonstrated that delaying necrosectomy translates to improved patient outcomes. Minimally invasive therapies have been described both for early and late management of necrotic pancreatic collections and fall into three broad categories: endoscopic, radiology assisted percutaneous drainage and laparoscopic or retroperitoneal surgical techniques. Such interventions may serve as temporizing measures delaying necrosectomy, but more importantly, as best demonstrated in recent randomized controlled trials, can serve as alternative approaches resulting in improved patient outcomes. Access to these techniques is based on their availability at expert centers. Minimally invasive therapies have increased in popularity, with a general consensus among experts being that reduced complications and mortality rates are realized by approaches other than open necrosectomy. However, additional well-designed, randomized trials are needed.
Collapse
Affiliation(s)
- Jeffrey J Easler
- Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh, PA, USA
| | | | | |
Collapse
|