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Liao Y, Zhang W, Huang Z, Yang L, Lu M. Diagnostic and prognostic value of miR-146b-5p in acute pancreatitis. Hereditas 2025; 162:93. [PMID: 40450371 DOI: 10.1186/s41065-025-00466-9] [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: 01/15/2025] [Accepted: 05/26/2025] [Indexed: 06/03/2025] Open
Abstract
OBJECTIVE MicroRNAs hold great potential as biomarkers for assessing the progression of acute pancreatitis (AP). This study aimed to explore the value of miR-146b-5p in the diagnosis and prognosis of AP patients. METHODS 110 AP patients were included and divided into 40 severe AP (SAP) patients and 70 non-SAP patients based on disease severity. Serum miR-146b-5p levels were measured using RT-qPCR. The diagnostic value of miR-146b-5p was evaluated utilizing ROC curves. Pearson correlation coefficient was employed to analyze the correlations between APACHEII, BISAP, and MCTSI scores and miR-146b-5p levels. The AP cell model was constructed by treating AR42J cells with deoxycholic acid (DCA), the proliferative capacity of cells was measured with CCK-8, apoptosis was measured by flow cytometry, and IL-6 and IL-8 protein levels were analyzed by ELISA. RESULTS Serum miR-146b-5p levels were decreased in SAP and unfavorable patients. Serum miR-146b-5p was able to effectively differentiate between SAP and non-SAP patients, and also effectively differentiate between unfavorable and favorable patients. MiR-146b-5p levels were significantly negatively correlated with APACHEII score (r=-0.6676), BISAP score (r=-0.5696), and MCTSI score (r=-0.5857). Furthermore, in the AP cell model, miR-146b-5p expression was down-regulated, proliferative capacity was diminished, apoptosis was increased, and IL-6 and IL-8 levels were elevated, but overexpression of miR-146b-5p partially reversed these changes. CONCLUSION miR-146b-5p expression is down-regulated in the serum of SAP patients and cells, and it has a good diagnostic effect. It may be a potential biomarker and therapeutic target for AP.
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Affiliation(s)
- Ying Liao
- Department of Critical Care Medicine, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, 341100, China
| | - Weiwei Zhang
- Department of Critical Care Medicine, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, 341100, China
| | - Zhenfei Huang
- Department of Critical Care Medicine, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, 341100, China
| | - Liu Yang
- Department of Critical Care Medicine, Ganzhou People's Hospital, Ganzhou City, Jiangxi Province, 341100, China
| | - Mingjin Lu
- Supply Room, The Fifth People's Hospital of Ganzhou, No. 666, Dongjiangyuan Avenue, Shuixi Town, Zhanggong District, Ganzhou City, Jiangxi Province, 341000, China.
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Sastre J, Pérez S, Sabater L, Rius-Pérez S. Redox signaling in the pancreas in health and disease. Physiol Rev 2025; 105:593-650. [PMID: 39324871 DOI: 10.1152/physrev.00044.2023] [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: 12/04/2023] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/27/2024] Open
Abstract
This review addresses oxidative stress and redox signaling in the pancreas under healthy physiological conditions as well as in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. Physiological redox homeodynamics is maintained mainly by NRF2/KEAP1, NF-κB, protein tyrosine phosphatases, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), and normal autophagy. Depletion of reduced glutathione (GSH) in the pancreas is a hallmark of acute pancreatitis and is initially accompanied by disulfide stress, which is characterized by protein cysteinylation without increased glutathione oxidation. A cross talk between oxidative stress, MAPKs, and NF-κB amplifies the inflammatory cascade, with PP2A and PGC1α as key redox regulatory nodes. In acute pancreatitis, nitration of cystathionine-β synthase causes blockade of the transsulfuration pathway leading to increased homocysteine levels, whereas p53 triggers necroptosis in the pancreas through downregulation of sulfiredoxin, PGC1α, and peroxiredoxin 3. Chronic pancreatitis exhibits oxidative distress mediated by NADPH oxidase 1 and/or CYP2E1, which promotes cell death, fibrosis, and inflammation. Oxidative stress cooperates with mutant KRAS to initiate and promote pancreatic adenocarcinoma. Mutant KRAS increases mitochondrial reactive oxygen species (ROS), which trigger acinar-to-ductal metaplasia and progression to pancreatic intraepithelial neoplasia (PanIN). ROS are maintained at a sufficient level to promote cell proliferation, while avoiding cell death or senescence through formation of NADPH and GSH and activation of NRF2, HIF-1/2α, and CREB. Redox signaling also plays a fundamental role in differentiation, proliferation, and insulin secretion of β-cells. However, ROS overproduction promotes β-cell dysfunction and apoptosis in type 1 and type 2 diabetes.
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Affiliation(s)
- Juan Sastre
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
| | - Salvador Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
| | - Luis Sabater
- Liver, Biliary and Pancreatic Unit, Hospital Clínico, Department of Surgery, Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Sergio Rius-Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
- Department of Cell Biology, Functional Biology and Physical Anthropology, Faculty of Biology, University of Valencia, Valencia, Spain
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Briones-Andrade J, Ramírez-Santiago G, Romero-Arias JR. A mathematical model for pancreatic cancer during intraepithelial neoplasia. ROYAL SOCIETY OPEN SCIENCE 2024; 11:240702. [PMID: 39493299 PMCID: PMC11528534 DOI: 10.1098/rsos.240702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 08/20/2024] [Accepted: 09/11/2024] [Indexed: 11/05/2024]
Abstract
Cancer is the result of complex interactions of intrinsic and extrinsic cell processes, which promote sustained proliferation, resistance to apoptosis, reprogramming and reorganization. The evolution of any type of cancer emerges from the role of the microenvironmental conditions and their impact of some molecular complexes on certain signalling pathways. The understanding of the early onset of cancer requires a multiscale analysis of the cellular microenvironment. In this paper, we analyse a qualitative multiscale model of pancreatic adenocarcinoma by modelling the cellular microenvironment through elastic cell interactions and their intercellular communication mechanisms, such as growth factors and cytokines. We focus on the low-grade dysplasia (PanIN 1) and moderate dysplasia (PanIN 2) stages of pancreatic adenocarcinoma. To this end, we propose a gene-regulatory network associated with the processes of proliferation and apoptosis of pancreatic cells and its kinetics in terms of delayed differential equations to mimic cell development. Likewise, we couple the cell cycle with the spatial distribution of cells and the transport of growth factors to show that the adenocarcinoma evolution is triggered by inflammatory processes. We show that the oncogene RAS may be an important target for developing anti-inflammatory strategies that limit the emergence of more aggressive adenocarcinomas.
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Affiliation(s)
| | | | - J. Roberto Romero-Arias
- Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico
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Ren R, Ren W, Zhang Y, Zhang H, Su W, Hu R, Zhao J, He L, Mu Y, Cheng Y. Breaking the chain in organ failure: Role of umbilical cord and bone marrow derived mesenchymal stem cells in treatment of severe acute pancreatitis. Heliyon 2024; 10:e35785. [PMID: 39220979 PMCID: PMC11365331 DOI: 10.1016/j.heliyon.2024.e35785] [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: 02/03/2024] [Revised: 05/09/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
Background Previous studies showed that MSCs could mitigate damage in the pancreas during acute pancreatitis (AP). However, acute mortality associated with AP was more often a result of persistent failure of remote organs, rather than local damage, especially in severe acute pancreatitis (SAP), and the effect of MSCs may vary depending on their origin. Methods An SAP model was induced in 8-week C57BL/6 J male mice by retrograde injection of 5 % sodium taurocholate solution through the bile duct. SAP mice were divided into the SAP group, UC-MSCs group, and BMSCs group, which were treated with saline, 1 × 106 UC-MSCs, and 1 × 106 BMSCs respectively, through the tail vein. After treatment, serum markers, inflammation, and morphology were assessed in the pancreas, kidneys, lungs, and hearts. Results MSCs infusion ameliorated the systemic inflammatory response in SAP mice. In the MSCs-treated SAP mice, local tissue injury and inflammation response in the pancreas were alleviated. But more importantly, the renal and lung injury were all significantly and drastically mitigated, and the levels of pro-inflammatory factors such as IL-6, MCP-1, IL-1β, and TNF-α in the kidney, lung and heart were sharply decreased. In terms of origin, UC-MSCs exhibited superior efficacy compared with BMSCs. Furthermore, compared to the normal control mice, UC-MSCs showed an earlier appearance, higher distribution densities, and longer duration of presence in the injured tissue. Conclusions This study provides compelling evidence supporting the therapeutic potential of MSCs in SAP treatment and particularly their ability to mitigate multi-organ failure. Our results also suggested that UC-MSCs may offer greater advantages over BMSCs in SAP therapy.
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Affiliation(s)
- Rui Ren
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
- Medical School of Chinese People's Liberation Army, Beijing, 100853, China
| | - Weizheng Ren
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Yue Zhang
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
- Medical School of Chinese People's Liberation Army, Beijing, 100853, China
| | - Haixia Zhang
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
- Medical School of Chinese People's Liberation Army, Beijing, 100853, China
| | - Wanlu Su
- Medical School of Chinese People's Liberation Army, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, 300071, China
| | - Ruofan Hu
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
- Medical School of Chinese People's Liberation Army, Beijing, 100853, China
| | - Jian Zhao
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
- Medical School of Chinese People's Liberation Army, Beijing, 100853, China
| | - Lei He
- Department of Hepatopancreatobiliary Surgery, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Yiming Mu
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
| | - Yu Cheng
- Department of Endocrinology, The First Clinical Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100853, China
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Cirak Z, Tanoglu A, Yeniceri M, Tanoglu EG, Kaplan M, Sade AG. Certolizumab Has Favorable Efficacy on Preventing Pancreas and Target Organs Damage in Acute Pancreatitis. Pancreas 2024; 53:e588-e594. [PMID: 38986079 DOI: 10.1097/mpa.0000000000002343] [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: 07/12/2024]
Abstract
OBJECTIVE It was targeted to assess the efficacy of certolizumab on pancreas and target organs via biochemical parameters and histopathologic scores in experimental acute pancreatitis (AP). MATERIALS AND METHODS Forty male Sprague Dawley rats were divided into the following 5 equal groups: group 1 (sham group), group 2 (AP group), group 3 (AP + low-dose certolizumab group), group 4 (AP + high-dose certolizumab group), and group 5 (placebo group). Rats in all groups were sacrificed 24 hours after the last injection and amylase, tumor necrosis factor α, transforming growth factor β, interleukin 1β, malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were studied in blood samples. Histopathological investigation of both the pancreas and target organs (lungs, liver, heart, kidneys) was performed by a pathologist blind to the groups. In silico analysis were also accomplished. RESULTS The biochemical results in the certolizumab treatment groups were identified to be significantly favorable compared to the AP group (P < 0.001). The difference between the high-dose group (group 4) and low-dose treatment group (group 3) was found to be significant in terms of biochemical parameters and histopathological scores (P < 0.001). In terms of the effect of certolizumab treatment on the target organs (especially on lung tissue), the differences between the low-dose treatment group (group 3) and high-dose treatment group (group 4) with the AP group (group 2) were significant. CONCLUSIONS Certolizumab has favorable protective effects on pancreas and target organs in AP. It may be a beneficial agent for AP treatment and may prevent target organ damage.
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Affiliation(s)
- Zafer Cirak
- From the Department of Internal Medicine, Honaz State Hospital
| | - Alpaslan Tanoglu
- Department of Internal Medicine, Division of Gastroenterology, Bahçeşehir University, Faculty of Medicine
| | - Murat Yeniceri
- University of Health Sciences, Institution of Hamidiye Health Sciences, Department of Molecular Biology and Genetics
| | - Esra Guzel Tanoglu
- Department of Internal Medicine, University of Health Sciences, Bakırköy Dr. Sadi Konuk Hospital
| | - Mustafa Kaplan
- Department of Internal Medicine, University of Health Sciences, Sultan Abdülhamid Han Hospital
| | - Ayşe Gökcen Sade
- Department of Pathology, University of Health Sciences, Sultan Abdülhamid Han Hospital, Istanbul, Turkey
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Jiang Y, Wu H, Peng Y, He P, Qian S, Lin H, Chen H, Qian R, Wang D, Chu M, Ji W, Guo X, Shan X. Gastrodin ameliorates acute pancreatitis by modulating macrophage inflammation cascade via inhibition the p38/NF-κB pathway. Int Immunopharmacol 2024; 129:111593. [PMID: 38290206 DOI: 10.1016/j.intimp.2024.111593] [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: 11/05/2023] [Revised: 01/18/2024] [Accepted: 01/23/2024] [Indexed: 02/01/2024]
Abstract
Acute pancreatitis (AP) is a prevalent, destructive, non-infectious pancreatic inflammatory disease, which is usually accompanied with systemic manifestations and poor prognosis. Gastrodin (4-hydroxybenzyl alcohol 4-O-β-d-glucopyranoside) has ideal anti-inflammatory effects in various inflammatory diseases. However, its potential effects on AP had not been studied. In this study, serum biochemistry, H&E staining, immunohistochemistry, immunofluorescence, western blot, real-time quantitative PCR (RT-qPCR) were performed to investigate the effects of Gastrodin on caerulein-induced AP pancreatic acinar injury model in vivo and lipopolysaccharide (LPS) induced M1 phenotype macrophage model in vitro. Our results showed that Gastrodin treatment could significantly reduce the levels of serum amylase and serum lipase while improving pancreatic pathological morphology. Additionally, it decreased secretion of inflammatory cytokines and chemokines, and inhibited the levels of p-p38/p38, p-IκB/IκB as well as p-NF-κB p-p65/NF-κB p65. Overall our findings suggested that Gastrodin might be a promising therapeutic option for patients with AP by attenuating inflammation through inhibition of the p38/NF-κB pathway mediated macrophage cascade.
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Affiliation(s)
- Yalan Jiang
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Huilan Wu
- Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Yongmiao Peng
- Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Pingping He
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Songwei Qian
- Department of General Surgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Hongzhou Lin
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Huihui Chen
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Rengcheng Qian
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Dexuan Wang
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Maoping Chu
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
| | - Weiping Ji
- Department of General Surgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
| | - Xiaoling Guo
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
| | - Xiaoou Shan
- Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
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Zheng C, Zheng Y, Zheng Z. Therapeutic plasma exchange decreases serum triglyceride level rapidly and reduces early recurrence rate but no advantages in improving outcomes for patients with hyperlipidemic acute pancreatitis: a retrospective propensity score matching analysis based on twenty year's experience. BMC Endocr Disord 2024; 24:32. [PMID: 38443883 PMCID: PMC10916013 DOI: 10.1186/s12902-024-01562-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 02/23/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND Hyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study. METHODS A retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups. RESULTS A total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P = .589), local complications (P = .451) or motality between two groups. CONCLUSIONS TPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty.
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Affiliation(s)
- Canbin Zheng
- Department of Endocrine and Metabolic Disease, Shantou Central Hospital, Shantou, Guangdong, China
| | - Yongping Zheng
- Department of Gastroenterology, Shantou Central Hospital, 114 Waima Road, Shantou,, 515031, Guangdong, China.
| | - Zihui Zheng
- Department of Anesthesiology, Shantou Central Hospital, Shantou, Guangdong, China
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Jamal S, Shaw M, Quasim T, Puxty K, McGovern C. Long term opioid use after burn injury: a retrospective cohort study. Br J Anaesth 2024; 132:599-606. [PMID: 38216388 PMCID: PMC10870133 DOI: 10.1016/j.bja.2023.12.003] [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: 07/03/2023] [Revised: 11/30/2023] [Accepted: 12/04/2023] [Indexed: 01/14/2024] Open
Abstract
BACKGROUND Patients who have survive a burn injury might be at risk of opioid dependence after discharge. This study examined the use of opioids in patients who suffer burn injury and explored factors associated with persistent opioid use after hospital discharge. METHODS This retrospective cohort study compared adults admitted with a burn injury from 2009 to 2019 with two matched comparison cohorts from the general population and adults with a diagnosis of acute pancreatitis. Pre-admission prescription opioid use was determined, and a multivariable negative binomial regression analysis used to explore post-discharge opioid use. RESULTS A total of 7147 burn patients were matched with 6810 pancreatitis patients and with 28 184 individuals from the general population. Pre-admission opioid use was higher in the burn and pancreatitis cohorts (29% and 40%, respectively) compared with the general population (17%). Opioid use increased in both burn and pancreatitis cohorts after discharge (41% and 53%, respectively), although patients with pancreatitis were at even higher risk of increased opioid use in an adjusted analysis (incidence rate ratio 1.43). Female sex, lower socioeconomic status, ICU admission, pre-injury opioid use, and a history of excess alcohol use were all associated with an increase in opioid prescriptions after discharge. CONCLUSIONS Opioid use is high in those admitted with a burn injury or acute pancreatitis when compared with the general population, increasing further after hospital discharge. Female sex and socioeconomic deprivation are among factors that make increased opioid use more likely, although this phenomenon seems even more pronounced in those with acute pancreatitis compared with burn injuries.
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Affiliation(s)
- Sherzah Jamal
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK.
| | - Martin Shaw
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Tara Quasim
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Kathryn Puxty
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
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Poulsen VV, Hadi A, Werge MP, Karstensen JG, Novovic S. Circulating Biomarkers Involved in the Development of and Progression to Chronic Pancreatitis-A Literature Review. Biomolecules 2024; 14:239. [PMID: 38397476 PMCID: PMC10887223 DOI: 10.3390/biom14020239] [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: 12/29/2023] [Revised: 02/13/2024] [Accepted: 02/16/2024] [Indexed: 02/25/2024] Open
Abstract
Chronic pancreatitis (CP) is the end-stage of continuous inflammation and fibrosis in the pancreas evolving from acute- to recurrent acute-, early, and, finally, end-stage CP. Currently, prevention is the only way to reduce disease burden. In this setting, early detection is of great importance. Due to the anatomy and risks associated with direct sampling from pancreatic tissue, most of our information on the human pancreas arises from circulating biomarkers thought to be involved in pancreatic pathophysiology or injury. The present review provides the status of circulating biomarkers involved in the development of and progression to CP.
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Affiliation(s)
- Valborg Vang Poulsen
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - Amer Hadi
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - Mikkel Parsberg Werge
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
| | - John Gásdal Karstensen
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
- Department of Clinical Medicine, University of Copenhagen, 2000 Copenhagen, Denmark
| | - Srdan Novovic
- Pancreatitis Center East, Gastrounit, Copenhagen University Hospital—Amager and Hvidovre, 2000 Copenhagen, Denmark; (V.V.P.); (A.H.); (M.P.W.); (J.G.K.)
- Department of Clinical Medicine, University of Copenhagen, 2000 Copenhagen, Denmark
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Liu S, Luo W, Szatmary P, Zhang X, Lin JW, Chen L, Liu D, Sutton R, Xia Q, Jin T, Liu T, Huang W. Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19. Int J Mol Sci 2023; 24:3246. [PMID: 36834656 PMCID: PMC9964039 DOI: 10.3390/ijms24043246] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.
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Affiliation(s)
- Shiyu Liu
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wenjuan Luo
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Peter Szatmary
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BE, UK
| | - Xiaoying Zhang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jing-Wen Lin
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Lu Chen
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
| | - Dan Liu
- Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Robert Sutton
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BE, UK
| | - Qing Xia
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Tao Jin
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Tingting Liu
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wei Huang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
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11
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Ding X, Chen B. Effect of Aggressive Intravenous Fluid Resuscitation Versus Nonaggressive Fluid Resuscitation in the Treatment of Acute Pancreatitis: A Systematic Review and Meta-Analysis. Pancreas 2023; 52:e89-e100. [PMID: 37523599 DOI: 10.1097/mpa.0000000000002230] [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: 08/02/2023]
Abstract
OBJECTIVES Despite the need for active fluid therapy, fluid management of most acute pancreatitis (AP) cases is still supportive. The aim of this review is to compare the effect of aggressive versus nonaggressive intravenous (IV) fluid resuscitation in the treatment of acute pancreatitis. METHODS A systematic search of medical databases, such as Medline, Google Scholar, Science Direct, Cochrane Central, was conducted for publication until April 2022. We included randomized controlled trials or cohort (prospective and retrospective) studies reporting the outcomes of AP in patients that were managed with aggressive and nonaggressive IV fluid resuscitation. The primary outcome of interest was in-hospital mortality. RESULTS Fourteen trials involving 3423 acute pancreatitis patients were included in the review. We did not observe any differences in the risk of mortality, persistent organ failure, and systemic inflammatory response syndrome in both study groups. However, there was an increased risk of development of pancreatic necrosis, renal failure, and respiratory failure in the aggressive fluid therapy group compared with nonaggressive therapy. The funnel plot showed no publication bias. CONCLUSIONS Aggressive fluid therapy did not improve mortality rates in acute AP patients and was associated with an increased risk of acute renal failure, and respiratory failure.
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Affiliation(s)
| | - Bo Chen
- Department of Gastroenterology, QiLu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China
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12
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Yan X, Lin T, Zhu Q, Zhang Y, Song Z, Pan X. Naringenin protects against acute pancreatitis-associated intestinal injury by inhibiting NLRP3 inflammasome activation via AhR signaling. Front Pharmacol 2023; 14:1090261. [PMID: 36713830 PMCID: PMC9881748 DOI: 10.3389/fphar.2023.1090261] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 01/02/2023] [Indexed: 01/15/2023] Open
Abstract
Background: In this study, we examined the functions and mechanisms by which naringenin protects against SAP (severe acute pancreatitis)-related intestinal injury by modulating the AhR/NLRP3 signaling pathway. Material and methods: Fifteen healthy male C57BL/6 mice were randomly divided into SAP (n = 12) and normal (n = 3) groups. Mice in the SAP group received caerulein and lipopolysaccharide intraperitoneal injections and were then randomly assigned to the SAP, NAR, CH223191, and Dexamethasone (DEX) groups. Pathological changes in the pancreatic and intestinal mucosa were observed by Hematoxylin & Eosin (H&E) staining. In vitro, RAW264.7 cells were exposed to lipopolysaccharide and treated with naringenin. The levels of NLRP3, AhR, IL-1β, TNF, and IL-6 in the SAP model and RAW264.7 cells were evaluated by enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. The nuclear translocation of AhR was shown by immunofluorescence. AutoDockTools was used to predict the conformations of naringenin-AhR binding, and PyMol 2.4 was used to visualize the conformations. Results: Mouse pancreatic and intestinal injury was alleviated by treatment with naringenin. Naringenin inhibited the activation of the NLRP3 inflammasome and inhibited damage to intestinal tight junctions. Moreover, naringenin increased AhR nuclear translocation and activated the AhR pathway. Conclusion: Naringenin can reduce SAP-associated intestinal injury by inhibiting the activation of the NLRP3 inflammasome via the AhR signaling pathway.
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Affiliation(s)
| | | | | | | | | | - Xinting Pan
- The Affiliated Hospital of Qingdao University, Qingdao, China
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13
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Wiseman SM, Leong R, Lee D, Nabata K. Bibliometric analysis of the classic cited papers in the American Journal of Surgery: Citation recapitulates surgical history. Am J Surg 2023; 225:832-840. [PMID: 36635132 DOI: 10.1016/j.amjsurg.2023.01.005] [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: 12/09/2022] [Accepted: 01/06/2023] [Indexed: 01/08/2023]
Abstract
BACKGROUND We performed a bibliometric analysis of the American Journal of Surgery (AJS) to identify, characterize and place within a historical context, its published classic cited papers (CCPs). METHODS Bibliometric data from papers published in the AJS between January 1, 1945, and December 31, 2021 was extracted from the Web of Science database. Analysis was performed utilizing Bibliometrix and VOSViewer software. RESULTS 27,070 papers were published in the AJS over the study period. There were 16 CCPs, including 5 Top CCPs, identified. Review of the Top CCPs reveals that they are based on careful clinical observations, innovation and generally build on prior published work. Top CCPs usually are specific to a particular diagnosis or a commonly performed procedure, as such papers frequently present a scoring or classification system, or important details related to new operative approaches or techniques. CONCLUSIONS Bibliometric study of the AJS has allowed for identification, characterization and appreciation of many of the key changes that have occurred in the discipline throughout the history of modern surgery.
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Affiliation(s)
- Sam M Wiseman
- Department of Surgery, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, Canada.
| | - Rachel Leong
- Department of Surgery, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, Canada
| | - Debon Lee
- Department of Surgery, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, Canada
| | - Kylie Nabata
- Department of Surgery, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, Canada
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14
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Dasgupta T, Manickam V. Fibrosis in Liver and Pancreas: a Review on Pathogenic Significance, Diagnostic Options, and Current Management Strategies. Inflammation 2023; 46:824-834. [PMID: 36595108 DOI: 10.1007/s10753-022-01776-0] [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: 11/13/2022] [Revised: 12/15/2022] [Accepted: 12/16/2022] [Indexed: 01/04/2023]
Abstract
Inflammation is one of the most natural ways of the body's biological response against invading foreign pathogens or injured cells which eventually can lead to a chronic or acute productive response. Fibrosis is an end-stage event associated with an inflammatory response addressed with tissue hardening, discoloration, and most importantly overgrowth of associated tissue. Various organs at different diseased conditions are affected by fibrosis including the liver, pancreas, brain, kidney, and lung. Etiological factors including internal like inflammatory cytokines, growth factors, and oxidative stress and external like alcohol and viruses contribute to the development of fibrosis in both the liver and pancreas. More frequently, these organs are associated with pathogenic progression towards fibrosis from acute and chronic conditions and eventually fail in their functions. The pathogenesis of the organ-fibrotic events mainly depends on the activation of residential stellate cells; these cells help to accumulate collagen in respective organs. Various diagnostic options have been developed recently, and various therapeutic options are in trial to tackle fibrosis. In this review, an overview on fibrosis, the pathogenesis of fibrosis in the liver and pancreas, various diagnostic options developed in recent years, and possible present therapeutic measures to overcome options of fibrosis in the liver and pancreas; thus, restoring the functional status of organs is discussed.
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Affiliation(s)
- Tiasha Dasgupta
- Department of Bio Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India
| | - Venkatraman Manickam
- Department of Bio Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.
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15
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Zhu X, Duan F, Zhang Y, Wang X, Wang Y, Chen J, Zhang L, Wu M, Pan Z, Chen B. Acadesine alleviates acute pancreatitis-related lung injury by mediating the barrier protective function of pulmonary microvascular endothelial cells. Int Immunopharmacol 2022; 111:109165. [PMID: 35987144 DOI: 10.1016/j.intimp.2022.109165] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 08/06/2022] [Accepted: 08/11/2022] [Indexed: 11/16/2022]
Abstract
Severe acute pancreatitis (SAP) is a condition characterized by highly fatal acute inflammation and is usually associated with multiple organ dysfunction syndrome. Acute lung injury (ALI) is the most common complications of SAP, which is the accelerator of other organ dysfunction caused by SAP and the primary cause of early death due to SAP. Acadesine, an adenosine analog and an AMPK activator, has been discovered to modulate glucose and lipid metabolism, and inhibit the production of pro-inflammatory cytokines and iNOS. However, its role in SAP-ALI and its mechanism remains unclear and need to be explored. Herein, we discovered that acadesine mitigated the generation of reactive oxygen species (ROS) in human pulmonary microvascular endothelial cells (HPMECs), alleviated apoptosis and recovered barrier integrity, thereby contributing to anti-inflammatory effects in vitro and in vivo. Moreover, Nrf2 deficiency partially eliminated the effects of acadesine-induced antioxidant effects and thus weakened the protective effects on cells and Nrf2-knockout (Nrf2-/-) mice. This study demonstrates that acadesine attenuated SAP-ALI associated inflammation and tissue damage by modulating the Nrf2-dependent antioxidant pathway by triggering AMPK. These findings are of great significance for the treatment of SAP-related lung injury.
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Affiliation(s)
- Xiandong Zhu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Feixiang Duan
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Yan Zhang
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Xiaowu Wang
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Yongqiang Wang
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Jiawei Chen
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Lanyu Zhang
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Minmin Wu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China
| | - Zhuo Pan
- Department of General Surgery, First People's Hospital Affiliated to Huzhou Normal College, No. 158, Guangchang Hou Road, Huzhou, Zhejiang Province 313000, China
| | - Bicheng Chen
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
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16
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Chauhan R, Saxena N, Kapur N, Kardam D. Comparison of modified Glasgow-Imrie, Ranson, and Apache II scoring systems in predicting the severity of acute pancreatitis. POLISH JOURNAL OF SURGERY 2022; 95:6-12. [PMID: 36806163 DOI: 10.5604/01.3001.0015.8384] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
<b>Aim:</b> The course of acute pancreatitis is variable with patients at risk of poor outcomes. The purpose of this study was to compare Modified Glasgow-Imrie, Ranson, and APACHE II scoring systems in predicting the severity of acute pancreatitis. </br></br> <b> Material and Methods: </b> After a brief history, clinical examination and qualifying inclusion criteria, 70 patients (41 women, 29 men) diagnosed with acute pancreatitis were included in the study. The three scores were calculated for each patient and evaluated for their role in the assessment of specific outcomes. </br></br> <b>Results:</b> 34.3% patients were diagnosed with severe acute pancreatitis, while 65.7% patients had mild acute pancreatitis. A strong positive correlation was found between all the prognostic scores and the severity of disease. In the prediction of the severity of disease according to AUC, it was found that Glasgow-Imrie score had an AUC of 0.864 (0.7560.973), followed very closely by APACHE II score with an AUC of 0.863 (0.7580.968). APACHE II had the highest sensitivity (79.17%) in predicting severity while Glasgow-Imrie score was the most specific (97.83%) of all the scores. Patients with a Glasgow-Imrie score above the cut-off value of 3 had more complications and a longer hospital stay. </br></br> <b>Conclusion:</b> The Glasgow-Imrie score was comparable to APACHE II score and better than Ranson score statistically in predicting the severity of acute pancreatitis. Its administration in predicting the severity of acute pancreatitis is recommended.
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Affiliation(s)
- Rohit Chauhan
- Department of General & Minimally Invasive Surgery, Atal Bihari Vajpayee Institute of Medical Sciences & Dr. Ram Manohar Lohia Hospital, New Delhi, India
| | - Neeraj Saxena
- Department of General & Minimally Invasive Surgery, Atal Bihari Vajpayee Institute of Medical Sciences & Dr. Ram Manohar Lohia Hospital, New Delhi, India
| | - Neeti Kapur
- Department of General & Minimally Invasive Surgery, Atal Bihari Vajpayee Institute of Medical Sciences & Dr. Ram Manohar Lohia Hospital, New Delhi, India
| | - Dinesh Kardam
- Department of General & Minimally Invasive Surgery, Atal Bihari Vajpayee Institute of Medical Sciences & Dr. Ram Manohar Lohia Hospital, New Delhi, India
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17
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Yang X, Geng H, You L, Yuan L, Meng J, Ma Y, Gu X, Lei M. Rhein Protects Against Severe Acute Pancreatitis In vitro and In vivo by Regulating the JAK2/STAT3 Pathway. Front Pharmacol 2022; 13:778221. [PMID: 35370748 PMCID: PMC8969574 DOI: 10.3389/fphar.2022.778221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 02/28/2022] [Indexed: 01/30/2023] Open
Abstract
Rhein is widely used in inflammation treatment in China, but its effects on severe acute pancreatitis (SAP) have not been studied closely. This study investigated rhein’s protective effects against SAP using in vitro and in vivo models to determine whether its protective mechanism regulated the Janus kinase two and signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway. Thirty-six male Sprague–Dawley rats were randomised into sham operation, SAP and rhein groups. The SAP model was induced by retrograde pancreatic bile duct injection of sodium taurocholate. Serum TNF-α and interleukin (IL)-6 levels were determined by ELISA, whereas serum amylase and lipase concentrations were measured using test kits. Western blot and/or immunohistochemistry quantified JAK2 and STAT3 expression. Furthermore, histopathological pancreatic changes were detected by haematoxylin and eosin staining. AR42J cells were randomly divided into the control, cerulein and rhein groups. Amylase activity was assessed using an amylase test kit; the tumour necrosis factor-α (TNF-α) expression was determined by enzyme-linked immunosorbent assay (ELISA). JAK2 and STAT3 protein expression were evaluated by western blot. SAP was concomitant with increased JAK2 and STAT3 expressions in vivo. Pre-treatment with rhein attenuated serum TNF–α and IL-6 levels effectively, and notably reduced p-JAK2, p-STAT3, JAK2 and STAT3 protein expression. Rhein significantly alleviated pancreatic histopathology. Compared to untreated groups, rhein significantly reduced amylase activity in supernatants of AR42J cells induced by cerulein in vitro. Furthermore, rhein altered JAK2 and STAT3 protein levels in AR42J cells after cerulein induction. Overall, rhein exerted protective effect on SAP in vitro and in vivo, possibly through the JAK2/STAT3 signalling pathway.
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Affiliation(s)
- Xiaofang Yang
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Huan Geng
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lijiao You
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lin Yuan
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jialei Meng
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuhui Ma
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xuelian Gu
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ming Lei
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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18
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Effect of Early Continuous Veno-Venous Haemofiltration in Severe Acute Pancreatitis for the Prevention of Local Pancreatic Complications. Gastroenterol Res Pract 2022; 2022:7575231. [PMID: 35296066 PMCID: PMC8920652 DOI: 10.1155/2022/7575231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 02/12/2022] [Indexed: 12/27/2022] Open
Abstract
Objective To compare the conventional treatment and continuous veno-venous haemofiltration (CVVH) in severe acute pancreatitis (SAP) for the prevention of pseudocyst and walled-off necrosis. Patients and Methods. Forty-two patients were divided into two treatment groups: conventional treatment group contained 24 patients and CVVH had 18. Conventional treatment group patients were treated symptomatically and according to the causes. CVVH group patients were treated symptomatically, and CVVH was done within 2 hours of admission. Results In both groups, there was a decrease in amylase, lipase, CRP, IL-6, IL-10, TNF-alpha, Ranson score, Balthazar score, and APACHE-II score after 72 hours, but the decrease was significantly greater in CVVH patients. There were no any local pancreatic complications in CVVH patients, but 1 patient had an acute peripancreatic fluid collection, 2 patients had pseudocyst, and 2 patients had walled-off necrosis (WON), and a mortality one was seen in the conventional treatment group. Conclusion The present study shows that early CVVH may be able to prevent the formation of pseudocyst and win in SAP patients.
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19
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Ding L, Li J. FXYD domain containing ion transport regulator 5 (FXYD5) silencing promotes cell viability and alleviates inflammatory response in cerulein-induced AR42J cells by blocking JAK2/STAT3 signaling pathway. Bioengineered 2022; 13:2639-2647. [PMID: 35042436 PMCID: PMC8974200 DOI: 10.1080/21655979.2021.2023795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Acute pancreatitis (AP), which causes severe morbidity and mortality, is a heavy burden for people clinically and financially. This study was designed to explore the mechanism of AP and try to find effective therapies against AP. The expression of FXYD5 was interfered by performing transfection. RT-qPCR and Western blot were utilized to measure FXYD5 expression. In addition, the viability, apoptosis and inflammatory response were evaluated using CCK-8, TUNEL and ELISA, respectively. Moreover, Western blot was employed to measure the expressions of apoptosis-, inflammation- and signaling pathway-related proteins. FXYD5 was found to be overexpressed in AP patients and AP cell model. The results showed that in cerulein-induced AR42J cells, cell viability was remarkably increased, and apoptosis was inhibited compared to the normal FXYD5-expressing group because FXYD5 was downregulated. Similarly, in such cells, interference with FXYD5 significantly suppressed the inflammatory response. In addition, Western blot analysis revealed that JAK2/STAT3 signaling was also strongly inhibited by FXYD5 interference. However, the effect of FXYD5 downregulation was reversed upon simultaneous activation of JAK2/STAT3 signaling. In conclusion, downregulation of FXYD5 could promote cell viability and alleviate inflammatory response in cerulein-induced AP via blocking JAK2/STAT3 signaling pathway.
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Affiliation(s)
- Licheng Ding
- Department of Emergency, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu P.R. China
| | - Jie Li
- Department of Emergency, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Hubei Wuhan, P.R. China
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20
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Al-Fartusie F, Farhan M, Al-Bairmani H, Nabil N, Aldhaheri M, Al-Temimi R. Estimation of some vital trace elements in patients with acute pancreatitis: A case-control study. BRAZ J PHARM SCI 2022. [DOI: 10.1590/s2175-97902022e20639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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21
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Batcioglu K, Dogan T, Kustepe E, Uyumlu A, Yilmaztekin Y. Protective effect of Lycium barbarum on renal injury induced by acute pancreatitis in rats. Pharmacogn Mag 2022. [DOI: 10.4103/pm.pm_516_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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22
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Bharmal SH, Kimita W, Ko J, Petrov MS. Cytokine signature for predicting new-onset prediabetes after acute pancreatitis: A prospective longitudinal cohort study. Cytokine 2021; 150:155768. [PMID: 34823207 DOI: 10.1016/j.cyto.2021.155768] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 10/26/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND/PURPOSE Acute inflammation of the pancreas often leads to metabolic sequelae, the most common of which is new-onset prediabetes (and, ultimately, diabetes). However, there is a lack of studies on predictors of this sequela. The aim was to investigate whether cytokines/chemokines measured at baseline are predictive of new-onset prediabetes after acute pancreatitis (NOPAP). METHODS This was a prospective longitudinal cohort study (as part of the LACERTA project) that included 68 individuals with non-necrotising acute pancreatitis who had no diabetes mellitus. Of them, 17 individuals had prediabetes at baseline and during follow-up, 37 individuals had normoglycaemia at baseline and during follow-up, and 14 individuals had normoglycaemia at baseline and developed NOPAP during follow-up. A commercially available human cytokine/chemokine multiplex kit was used to measure a total of 28 analytes at baseline. Multinomial regression analyses were conducted to investigate the associations between the cytokines/chemokines and the three study groups. RESULTS Interleukin-1β and interferon γ significantly predicted progression to NOPAP with an odds ratio (95% confidence interval) of 1.097 (1.002, 1.201) and 1.094 (1.003, 1.192), respectively (after accounting for age, sex, body mass index, and aetiology of acute pancreatitis). None of the studied cytokines/chemokines showed statistically significant associations with the antecedent prediabetes group (after accounting for the above covariates). CONCLUSION Elevated levels of interleukin-1β and interferon γ in acute pancreatitis individuals with normoglycaemia at baseline may predict progression to NOPAP during follow-up.
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Affiliation(s)
| | - Wandia Kimita
- School of Medicine, University of Auckland, New Zealand
| | - Juyeon Ko
- School of Medicine, University of Auckland, New Zealand
| | - Maxim S Petrov
- School of Medicine, University of Auckland, New Zealand.
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23
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Lin Y, Yu S, Wu X, Huang L, Huang S, Huang Y, Ding J, Li D. Clinical analysis of the therapeutic effect of plasma exchange on hypertriglyceridemic acute pancreatitis: A retrospective study. Transfusion 2021; 62:72-81. [PMID: 34735720 DOI: 10.1111/trf.16724] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 10/08/2021] [Accepted: 10/08/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND The therapeutic effect of plasma exchange (PE) on hypertriglyceridemic acute pancreatitis (HTGAP) is unclear. Therefore, we aimed to explore this therapeutic effect. STUDY DESIGN AND METHODS This study included 204 patients with HTGAP who underwent treatment at two provincial tertiary grade A hospitals in Fujian Province from October 2012 to May 2021. Patients were divided into a conventional group and a PE group. The Student's t-test and chi-square test were used for data analysis. RESULTS Among 204 patients, 56 and 148 were included in the PE and conventional groups, respectively. After propensity score matching (PSM), the PE and conventional groups each had 42 patients. There was no significant difference in age; sex; pregnancy; comorbidities; laboratory findings; incidences of complications, and multiple organ dysfunction syndrome (MODS); organ support treatment; surgical rate; mortality; and hospital stay between the groups (p > 0.05). The total expenses were significantly higher in the PE group than in the conventional group (p < 0.05). There was no statistically significant difference in the times of PE; total volume of PE; incidences of complications, and MODS; organ support treatment; surgical rate; mortality; and hospital stay between the early PE and delayed PE groups (p > 0.05). All patients in the PE group and conventional group with acute renal failure had significantly higher D-dimer levels than those without acute renal failure (p < 0.05). DISCUSSION Compared with conventional treatment, PE does not have a better therapeutic effect on HTGAP. The D-dimer level can predict whether patients with HTGAP will have acute renal failure.
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Affiliation(s)
- Yongxu Lin
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Shufang Yu
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaofan Wu
- Department of Tuberculosis Ward 2, Wuhan Pulmonary Hospital, Wuhan, China
| | - Letong Huang
- School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Simei Huang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yongzhu Huang
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jian Ding
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Dan Li
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
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Zhu X, Xie B, Liang D, Qin W, Zhao L, Deng Y, Wen P, Xu F, Aschner M, Jiang Y, Ou S. Protective Effects of Sodium Para-aminosalicylic Acid on Manganese-Induced Damage in Rat Pancreas. Biol Trace Elem Res 2021; 199:3759-3771. [PMID: 33405079 DOI: 10.1007/s12011-020-02516-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 11/24/2020] [Indexed: 12/17/2022]
Abstract
Sodium p-aminosalicylic acid (PAS-Na) has been previously shown to protect the brain from manganese (Mn)-induced toxicity. However, the efficacy of PAS-Na in protecting other organs from Mn toxicity and the mechanisms associated with this protection have yet to be addressed. Therefore, here, we assessed pancreatic damage in response to Mn treatment and the efficacy of PAS-Na in limiting this effect, along with specific mechanisms that mediate PAS-Na's protection. Mn exposure led to increased blood Mn content in dose- and time-dependent manner. Furthermore, subchronic Mn exposure (20 mg/kg for 8 weeks) led to pancreatic damage in a dose-dependent manner. In addition, the elevated Mn levels increased iron and decreased zinc and magnesium content in the pancreas. These effects were noted even 8 weeks after Mn exposure cessation. Mn exposure also affected the levels of amylase, lipase, and inflammatory factors such as tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β). PAS-Na significantly inhibited the increase in Mn concentration in both blood and pancreas, restored Mn-induced pancreatic damage, reversed the Mn-induced alterations in metal levels, and restored amylase and lipase concentrations. Taken together, we conclude that in rats, PAS-Na shows pharmacological efficacy in protecting the pancreas from Mn-induced damage.
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Affiliation(s)
- Xiaojuan Zhu
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Bingyan Xie
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Dianyin Liang
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Wenxia Qin
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Lin Zhao
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Yue Deng
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Pingjing Wen
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Fang Xu
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
| | - Michael Aschner
- Albert Einstein College of Medicine, Bronx, NJ, 10461, USA
- IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Yueming Jiang
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China.
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China.
| | - Shiyan Ou
- Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
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25
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Joshi V, Dimri U, Gopalakrishnan A, Bhanuprakash AG, Gupta VK. Porcine scabies induces marked apoptosis, increased pro-inflammatory cytokines IL-1, TNF-α and shedding of ICAM-1. Parasite Immunol 2021; 43:e12878. [PMID: 34559899 DOI: 10.1111/pim.12878] [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: 08/02/2021] [Revised: 09/05/2021] [Accepted: 09/20/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND Scabies is one of the leading causes of morbidity in pigs worldwide. Limited data are available regarding the role of immune reactions in the development of porcine scabies. MATERIALS AND METHODS The aim of this study was to investigate key pro-inflammatory cytokines (IL-1, TNF-α), soluble variant of adhesion molecule ICAM-1 and mite-mediated apoptosis of peripheral leukocytes in 20 pigs with scabies, in addition to 10 healthy controls. The pigs with at least three typical clinical signs and found positive for Sarcoptes scabiei var. suis in microscopy were recruited for the present study. RESULTS IL-1 acted as the major pro-inflammatory cytokine as serum IL-1 concentrations showed significantly (p < .05) higher levels (7-fold increase) in cases than in controls. The minor cytokine TNF-α was 4-fold higher during scabies, and its mean serum concentration was significantly increased (p < .05) in cases when compared to healthy controls. Soluble ICAM-1 levels were significantly higher (p < .05) in all the pigs of infested group compared with the controls. The percentage of apoptotic and necrotic leukocytes was found to be significantly higher (p < .05) in scabies positive pigs as compared to the healthy controls. CONCLUSION It is concluded that systemic elevation in pro-inflammatory cytokines IL-1 and TNF-α, shedding of soluble ICAM-1 variant in peripheral blood and increased rate of host-cell apoptosis in peripheral leukocytes might be implicated in the immunopathology of naturally acquired porcine scabies.
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Affiliation(s)
- Vivek Joshi
- Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.,Animal Health Section, ICAR-National Research Centre on Mithun, Medziphema, Dimapur, Nagaland, India
| | - Umesh Dimri
- Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
| | - Arumugam Gopalakrishnan
- Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.,Resident Veterinary Services Section, Madras Veterinary College, Chennai, Tamil Nadu, India
| | | | - Vinod Kumar Gupta
- Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
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Zheng CB, Zheng ZH, Zheng YP. Therapeutic plasma exchange for hyperlipidemic pancreatitis: Current evidence and unmet needs. World J Clin Cases 2021; 9:5794-5803. [PMID: 34368298 PMCID: PMC8316951 DOI: 10.12998/wjcc.v9.i21.5794] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/24/2021] [Accepted: 05/26/2021] [Indexed: 02/06/2023] Open
Abstract
With changes in lifestyle and diet worldwide, the prevalence of hyperlipidemic acute pancreatitis (HLAP) has greatly increased, and it has become the most common cause of acute pancreatitis not due to gallstones or alcohol. There are many available therapies for HLAP, including oral lipid-lowering agents, intravenous insulin, heparin, and therapeutic plasmapheresis (TPE). It is believed that the risk and severity of HLAP increase with rising levels of serum triglycerides (TG), thus a rapid decrease in serum TG level is the key to the successful management of HLAP. TPE has emerged as an effective modality in rapidly reducing serum TG levels. However, due to its cost and accessibility, TPE remains poorly evaluated until now. Some studies revealed its efficacy in helping to treat and prevent the recurrence, while some studies suggested that TG levels were not correlated with disease severity, mortality, or length of hospital stay. Thus TPE might have no beneficial effect for the outcome. This article gives an overview of the published evidence of TPE in the treatment of HLAP and outlines current evidence regarding individual outcome predictors, adverse effects of the procedure, and TPE in special occasions such as for pregnant patients and patients with diabetic ketoacidosis. Future direction of TPE research for HLAP is also discussed in this review.
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Affiliation(s)
- Can-Bin Zheng
- Department of Endocrine and Metabolic Disease, Shantou Central Hospital, Shantou 515031, Guangdong Province, China
| | - Zi-Hui Zheng
- Nursing College, Guangdong Pharmaceutical University, Guangzhou 510000, Guangdong Province, China
| | - Yong-Ping Zheng
- Department of Gastroenterology, Shantou Central Hospital, Shantou 515031, Guangdong Province, China
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Yazbeck R, Jaenisch SE, Abbott CA. Dipeptidyl peptidase 4 inhibitors: Applications in innate immunity? Biochem Pharmacol 2021; 188:114517. [PMID: 33722535 PMCID: PMC7954778 DOI: 10.1016/j.bcp.2021.114517] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 03/04/2021] [Accepted: 03/05/2021] [Indexed: 12/25/2022]
Abstract
Dipeptidyl peptidase (DPP)-4 inhibitors are a class of orally available, small molecule inhibitors that prolong the insulinotropic activity of the incretin hormone glucagon-like peptide-1 (GLP-1) and are highly effective for the treatment of Type-2 diabetes. DPP4 can also cleave several immunoregulatory peptides including chemokines. Emerging evidence continues to implicate DPP4 inhibitors as immunomodulators, with recent findings suggesting DPP4 inhibitors modify specific aspects of innate immunity. This review summarises recent insights into how DPP4 inhibitors could be implicated in endothelial, neutrophil and monocyte/macrophage mediated immunity. Additionally, this review highlights additional avenues of research with DPP4 inhibitors in the context of the COVID-19 pandemic.
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Affiliation(s)
- R Yazbeck
- College of Medicine and Public Health & Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia; College of Science and Engineering, Flinders University, Adelaide, Australia.
| | - S E Jaenisch
- College of Medicine and Public Health & Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia; College of Science and Engineering, Flinders University, Adelaide, Australia.
| | - C A Abbott
- College of Medicine and Public Health & Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia; College of Science and Engineering, Flinders University, Adelaide, Australia.
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Wu Z, Lu G, Zhang L, Ke L, Yuan C, Ma N, Yu X, Guo X, Zhao W, Wang Y, Hu S, Wu D, Li W. Protectin D1 decreases pancreatitis severity in mice by inhibiting neutrophil extracellular trap formation. Int Immunopharmacol 2021; 94:107486. [PMID: 33639566 DOI: 10.1016/j.intimp.2021.107486] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/19/2020] [Accepted: 02/05/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Docosahexaenoic acid-derived protectin D1 (PD1) was identified critical in the resolution of inflammation in vivo, where it modulates the innate immune response and stimulates resolution. Acute pancreatitis (AP) is characterized by local pancreatic inflammation with mild forms whereas systemic inflammation with severe forms. Herein we investigate the impact of PD1 in murine models of pancreatitis. METHODS Three independent AP models, which induced in male mice via intraperitoneal injection of caerulein, L-arginine or pancreatic duct ligation, were used to confirm the protective effect of PD1. Infiltrationsof neutrophils and macrophages in pancreas were detected by flow cytometry and immunohistochemistry. In vitro and in vivo neutrophil extracellular traps formation was detected by immunofluorescence staining. Expression of peptidylarginine deiminase 4 (PAD4) in activated neutrophils was evaluated by western blotting. RESULTS Systemic treatment with PD1 reduced serum activities of amylase and lipase, blunted the concentrations of tumor necrosis factor-α and interleukin-6 in serum and protected against pancreas histologic damage in three AP models. PD1 also prolonged the survival in the pancreatic duct ligation model. Moreover, pancreatic infiltrationofneutrophils and neutrophil CitH3 expression were reduced after PD1 administration. In vitro studies revealed PD1 decreased supernatant cell-free DNA and CitH3 levels and downregulated PAD4 expression in mouse bone-marrow derived neutrophils. However, in the caerulein mice pretreated with GSK484 hydrochloride, an inhibitor of PAD4, PD1 treatment showed no more protective effect. CONCLUSIONS PD1 ameliorates AP by decreasing early infiltration of neutrophils into the pancreas and neutrophil extracellular traps formation through PAD4. These results supply the foundation to consider PD1 as a therapy for AP.
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Affiliation(s)
- Zhiyang Wu
- Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China
| | - Guotao Lu
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China
| | - Luyao Zhang
- Department of Pathology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 210023 Nanjing, China
| | - Lu Ke
- Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Chenchen Yuan
- Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Nan Ma
- Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Xianqiang Yu
- Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Xi Guo
- Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China
| | - Wei Zhao
- Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China
| | - Yingjie Wang
- Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China
| | - Sanyuan Hu
- Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Dawei Wu
- Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong 266035, China.
| | - Weiqin Li
- Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
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Sternby H, Hartman H, Thorlacius H, Regnér S. The Initial Course of IL1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α with Regard to Severity Grade in Acute Pancreatitis. Biomolecules 2021; 11:biom11040591. [PMID: 33920566 PMCID: PMC8073083 DOI: 10.3390/biom11040591] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/10/2021] [Accepted: 04/14/2021] [Indexed: 12/12/2022] Open
Abstract
Clinical reports on early immune dysregulation in acute pancreatitis (AP) are scarce. Herein we investigate the initial temporal development of selected biomarkers. Blood samples were taken at 0–24 and 25–48 h after onsets of AP were acquired. Mean values and temporal intermediate difference (delta-values) of IL-1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were calculated. Differences between severity groups, predictive capacity of the biomarkers and association with severe disease were analyzed. Paired comparison of samples (n = 115) taken at 0–24 and 25–48 h after onsets of AP showed a change over time for IL-1β, IL-6, IL-8 and IL-10 (p < 0.05) and a significant difference between severity groups after 24 h. In ROC-analysis an IL-6 cut-off level of 196.6 pg/mL could differentiate severe AP (sensitivity 81.9, specificity 91.3). The delta-values of IL-1β and IL-6 were significantly associated with severe outcomes (odds ratios 1.085 and 1.002, respectively). Data of this work demonstrate a distinct change in IL-1β, IL-8, IL-10 and IL-6 over the first 48 h after onset of AP. The temporal development of biomarkers can assist in the early stratification of the disease. Herein IL-1β and IL-6 were associated with severe disease, however the prognostic capacity of investigated biomarkers is low.
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Effects of sildenafil citrate on pancreatic and lung complications in an experimental L-arginine-induced acute pancreatitis model. GASTROENTEROLOGY REVIEW 2021; 16:29-35. [PMID: 33986885 PMCID: PMC8112277 DOI: 10.5114/pg.2021.104734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 04/16/2020] [Indexed: 11/17/2022]
Abstract
Aim In this study, we aimed to investigate the effects of sildenafil citrate on acute pancreatitis and pulmonary complications of the disease. Material and methods In this study, we used 21 male Wistar-Albino rats weighing between 185 and 230 g. The rats were divided into 3 groups. Group 1 rats (control group, n = 7) were administered intraperitoneal 0.9% NaCl injection. Group 2 (study group, n = 7) and Group 3 (treatment group, n = 7) rats were given 100 mg/100 gr L-arginine twice, with an interval of 1 h to create acute pancreatitis. Group 3 was also administered intraperitoneal 10 mg/kg/day sildenafil citrate in 2 equal doses, 30 min and 12 h after creation of AP. The pancreas and lungs of all rats were stained with haematoxylin and eosin and examined histopathologically. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), interleukin (IL) 1α (IL-1α), IL-6, tumor necrosis factor α (TNF-α), nitric oxide (NO) and ADMA levels were measured in blood samples. Results In the treatment group, levels of amylase, AST, ALT, LDH, IL-1, IL-6, TNF-α, and NO were lower. In addition, pancreas and lung oedema, and perivascular inflammation were significantly less on histopathological examination when compared to the study group (p < 0.001). The ADMA level was significantly higher in the treatment group when compared to the control and study groups. There was no acinar cell necrosis or haemorrhage in the treatment group. However, the difference was not regarded as statistically significant because sufficient acinar cell necrosis and haemorrhage could not be created in the study group. Conclusions Sildenafil citrate significantly decreases various biochemical and histopathological changes in the early phase of acute pancreatitis and protects pancreatic tissue.
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Lin T, Song J, Pan X, Wan Y, Wu Z, Lv S, Mi L, Wang Y, Tian F. Downregulating Gasdermin D Reduces Severe Acute Pancreatitis Associated with Pyroptosis. Med Sci Monit 2021; 27:e927968. [PMID: 33582700 PMCID: PMC7891845 DOI: 10.12659/msm.927968] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background Intestinal injury plays a key role in the pathogenesis of severe acute pancreatitis (SAP). In this study, we investigated the protective function of downregulated Gasdermin D (GSDMD) in intestinal damage in a mouse model of severe acute pancreatitis (SAP). Material/Methods Twenty-four healthy male C57BL/6 mice were randomly divided into 4 groups – the NS group, the siRNA-NS group, the SAP group, and the siRNA-SAP group – with 6 mice in each group. SAP was induced in mice by intraperitoneal injection of caerulein and lipopolysaccharide. The pathological changes of pancreatic and the intestinal mucosa and the relative gene and protein expressions in each group were compared, and the levels of GSDMD and serum IL-1β and IL-18 were evaluated after induction of the SAP model. Results The mice in the SAP group were in more serious condition than those in the siRNA-SAP group, with various degrees of edema and hemorrhage in the intestinal tract. Under an optical microscope, the pathological changes of pancreatic tissue such as edema, inflammatory cell infiltration, and the damage of lobular structural were gradually increased in the SAP group and the siRNA-NS group. In addition, intestinal mucosal damage and intestinal villus breakage were found in the SAP group and the siRNA-NS group, and the latter was lighter than the former. Compared with the SAP group, the level of GSDMD protein expression in the siRNA-SAP group was lower, and the serum levels of IL-1β and IL-18 were higher in the SAP group and siRNA-SAP group (P<0.05). Immunohistochemical analysis showed the occludin and ZO-1 proteins in the NS group had a strong brown linear signal, while the brown-positive signals were weaker in the siRNA-SAP group and the SAP group. Conclusions Downregulating GSDMD protein can reduce pancreatitis associated with pyroptosis.
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Affiliation(s)
- Tianjiao Lin
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Jingyu Song
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Xinting Pan
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Youdong Wan
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Ziqian Wu
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Shaoyan Lv
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Liangyu Mi
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Yunyun Wang
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
| | - Fei Tian
- Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
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Di Mauro D, Smith R, Wijesurendere C, Hubble S, Manzelli A. Does the Implementation of a Clinical Care Pathway Have an Impact on Early Intravenous Fluid Therapy of Acute Pancreatitis?: A Pilot Quality Improvement Study. Pancreas 2021; 50:189-195. [PMID: 33565794 DOI: 10.1097/mpa.0000000000001736] [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: 12/10/2022]
Abstract
OBJECTIVES Early intravenous fluid (IVF) resuscitation is crucial in the management of acute pancreatitis; variation in IVF prescription practice had been demonstrated. This pilot study aims to assess whether the implementation of an Acute Pancreatitis Care Pathway (APCP) produces a change toward a more adequate IVF regimen in the first 24 hours. METHODS Patients with confirmed diagnosis of acute pancreatitis, from July 2015 to February 2016 (group 1) and from September 2017 to March 2018 (group 2), were considered. The APCP was developed between March 2016 and August 2017. Median IVF rate, volume, and type infused in the first 24 hours, were compared between groups. Nonparametric data were analyzed with the Mann-Whitney U test, differences in frequencies with the McNemar test; significance was set at P < 0.05. RESULTS Seventy-two patients were included, 36 in each group. In the first 24 hours, the median IVF rate was 177 mL/h vs 225 mL/h (P = 0.004); Ringer lactate infusion was 30% vs 77.8% (P = 0.0003). The median total IVF volume did not differ between groups. CONCLUSIONS The implementation of the APCP has the potential to lead to a successful change in early IVF resuscitation practice.
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Affiliation(s)
- Davide Di Mauro
- From the Department of Upper GI Surgery, Royal Devon and Exeter NHS Foundation Trust, Exeter
| | - Radford Smith
- Department of Surgery, Norwich & Norfolk University Hospitals NHS Foundation Trust, Norwich, United Kingdom
| | | | - Sheena Hubble
- From the Department of Upper GI Surgery, Royal Devon and Exeter NHS Foundation Trust, Exeter
| | - Antonio Manzelli
- From the Department of Upper GI Surgery, Royal Devon and Exeter NHS Foundation Trust, Exeter
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Xie X, Zhao J, Gao W, Chen J, Hu B, Cai X, Zheng Y. Prussian blue nanozyme-mediated nanoscavenger ameliorates acute pancreatitis via inhibiting TLRs/NF-κB signaling pathway. Theranostics 2021; 11:3213-3228. [PMID: 33537083 PMCID: PMC7847676 DOI: 10.7150/thno.52010] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 12/14/2020] [Indexed: 12/14/2022] Open
Abstract
Rationale: Acute pancreatitis (AP) is a serious acute condition affecting the abdomen and shows high morbidity and mortality rates. Its global incidence has increased in recent years. Inflammation and oxidative stress are potential therapeutic targets for AP. This study was conducted to investigate the intrinsic anti-oxidative and anti-inflammatory effects of Prussian blue nanozyme (PBzyme) on AP, along with its underlying mechanism. Methods: Prussian blue nanozymes were prepared by polyvinylpyrrolidone modification method. The effect of PBzyme on inhibiting inflammation and scavenging reactive oxygen species was verified at the cellular level. The efficacy and mechanism of PBzyme for prophylactically treating AP were evaluated using the following methods: serum testing in vivo, histological scoring following hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence staining, polymerase chain reaction array, Kyoto Encyclopedia of Genes and Genomes analysis and Western blotting analysis. Results: The synthetic PBzyme showed potent anti-oxidative and anti-inflammatory effects in reducing oxidative stress and alleviating inflammation both in vitro and in vivo in the prophylactic treatment of AP. The prophylactic therapeutic efficacy of PBzyme on AP may involve inhibition of the toll-like receptor/nuclear factor-κB signaling pathway and reactive oxygen species scavenging. Conclusion: The single-component, gram-level mass production, stable intrinsic biological activity, biosafety, and good therapeutic efficacy suggest the potential of PBzyme in the preventive treatment of AP. This study provides a foundation for the clinical application of PBzyme.
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Affiliation(s)
- Xue Xie
- Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, P. R. China
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University. Chongqing 400010, P. R. China
| | - Jiulong Zhao
- Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P. R. China
| | - Wei Gao
- Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, P. R. China
| | - Jie Chen
- Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, P. R. China
| | - Bing Hu
- Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, P. R. China
| | - Xiaojun Cai
- Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, P. R. China
| | - Yuanyi Zheng
- Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, P. R. China
- Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, P. R. China
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The Effect of Enteral Nutrition on Intra-Abdominal Pressure in Severe Acute Pancreatitis Patients. Int Surg 2020. [DOI: 10.9738/intsurg-d-13-00181.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Thiruvengadam NR, Kochman ML. Emerging Therapies to Prevent Post-ERCP Pancreatitis. Curr Gastroenterol Rep 2020; 22:59. [PMID: 33188441 DOI: 10.1007/s11894-020-00796-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW The aim of this review is to evaluate emerging, novel therapies for the prevention of post-ERCP pancreatitis. RECENT FINDINGS Rectal indomethacin reduces the risk of pancreatitis in low- and average-risk patients, who comprise the majority of patients undergoing ERCP. An 8-h protocol of aggressive lactated Ringer's reduces the risk of pancreatitis in average-risk patients. Sublingual nitrate may provide additional benefit to rectal NSAIDs in preventing PEP. A tacrolimus trough > 2.5 ng/mL was recently shown to be associated with a lower risk of PEP in liver transplant patients undergoing ERCP. Routine usage of rectal indomethacin in all patients undergoing ERCP reduces the risk of PEP. Pancreatic-duct stents reduce the risk of PEP in high-risk patients. There is emerging data that aggressive hydration with lactated Ringer's and nitrates may further reduce PEP. Tacrolimus is a promising potential agent to prevent PEP but needs further clinical study.
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Affiliation(s)
- Nikhil R Thiruvengadam
- Division of Gastroenterology and Hepatology, University of California San Francisco, 513 Parnassus Avenue, S-357, Box 0538, San Francisco, CA, 94143-0538, USA. .,Gastroenterology Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
| | - Michael L Kochman
- Gastroenterology Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Center for Endoscopic Innovation, Research and Training, Perelman School of Medicine, Philadelphia, PA, USA
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Sun H, Tian J, Li J. MiR-92b-3p ameliorates inflammation and autophagy by targeting TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells. Int Immunopharmacol 2020; 88:106691. [PMID: 32822908 DOI: 10.1016/j.intimp.2020.106691] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 05/20/2020] [Accepted: 06/08/2020] [Indexed: 02/08/2023]
Abstract
Acute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality. Dysregulation of microRNAs (miRNAs) was involved in human diseases, including AP. However, the effects of miR-92b-3p on AP process and its mechanism remain not been fully clarified. The expression levels of miR-92b-3p and tumor necrosis factor receptor-associated factor-3 (TRAF3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of TRAF3, tumor necrosis factor α (TNF-α) TNF-α, interleukin-6 (IL-6), phosphorylated mitogen-activated protein kinase kinase 3 (p-MKK3), MKK3, p38 and phosphorylated p38 (p-p38) were detected by western blot. The concentration of TNF-α and IL-6 in the medium was measured using ELISA kits. The possible binding sites of miR-92b-3p and TRAF3 were predicted by TargetScan and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression level of miR-92b-3p was decreased and TRAF3 expression was increased in AR42J cells stimulated with caerulein. Moreover, the protein levels of pro-inflammatory cytokines (TNF-α and IL-6) were markedly elevated, and the expression levels of autophagy-related markers Beclin1 as well as the ratio of LC3-II/I were obviously increased in AR42J cells treated with caerulein. In addition, overexpression of miR-92b-3p or knockdown of TRAF3 significantly suppressed the release of pro-inflammatory cytokines and autophagy in caerulein-induced AR42J cells. Furthermore, TRAF3 was a direct target of miR-92b-3p and its upregulation reversed the effects of miR-92b-3p overexpression on inflammatory response and autophagy. Besides, overexpression of miR-92b-3p inhibited the activation of the MKK3-p38 pathway by affecting TRAF3 expression. In conclusion, miR-92b-3p attenuated inflammatory response and autophagy by downregulating TRAF3 and suppressing MKK3-p38 pathway in caerulein-induced AR42J cells, providing a novel avenue for treatment of AP.
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Affiliation(s)
- Hongzhi Sun
- Department of Critical Care Medicine, The Second Hospital of Jilin University, No 218 Ziqiang Street, Nanguan District 130041, Changchun, China
| | - Jiakun Tian
- Department of Critical Care Medicine, The Second Hospital of Jilin University, No 218 Ziqiang Street, Nanguan District 130041, Changchun, China
| | - Jinliang Li
- Department of Critical Care Medicine, The Second Hospital of Jilin University, No 218 Ziqiang Street, Nanguan District 130041, Changchun, China.
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López-Iranzo FJ, López-Rodas AM, Franco L, López-Rodas G. Pentoxifylline and Oxypurinol: Potential Drugs to Prevent the "Cytokine Release (Storm) Syndrome" Caused by SARS-CoV-2? Curr Pharm Des 2020; 26:4515-4521. [PMID: 32787748 DOI: 10.2174/1381612826666200811180232] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 07/09/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND COVID-19, caused by SARS-CoV-2, is a potentially lethal, rapidly-expanding pandemic and many efforts are being carried out worldwide to understand and control the disease. COVID-19 patients may display a cytokine release syndrome, which causes severe lung inflammation, leading, in many instances, to death. OBJECTIVE This paper is intended to explore the possibilities of controlling the COVID-19-associated hyperinflammation by using licensed drugs with anti-inflammatory effects. HYPOTHESIS We have previously described that pentoxifylline alone, or in combination with oxypurinol, reduces the systemic inflammation caused by experimentally-induced pancreatitis in rats. Pentoxifylline is an inhibitor of TNF-α production and oxypurinol inhibits xanthine oxidase. TNF-α, in turn, activates other inflammatory genes such as Nos2, Icam or IL-6, which regulate migration and infiltration of neutrophils into the pulmonary interstitial tissue, causing injury to the lung parenchyma. In acute pancreatitis, the anti-inflammatory action of pentoxifylline seems to be mediated by the prevention of the rapid and presumably transient loss of PP2A activity. This may also occur in the hyperinflammatory -cytokine releasing phase- of SARS-CoV-2 infection. Therefore, it may be hypothesized that early treatment of COVID-19 patients with pentoxifylline, alone or in combination with oxypurinol, would prevent the potentially lethal acute respiratory distress syndrome. CONCLUSION Pentoxifylline and oxypurinol are licensed drugs used for diseases other than COVID-19 and, therefore, phase I clinical trials would not be necessary for the administration to SARS-CoV-2- infected people. It would be worth investigating their potential effects against the hyperinflammatory response to SARS-CoV-2 infection.
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Affiliation(s)
- Francisco J López-Iranzo
- Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain,Residential Centre for Elderly People, Savia-Requena, Spain
| | - Ana M López-Rodas
- Medical Specialist in Family and Community Medicine, SAMU Service, Hospital of Sagunto, Spain,Royal Academy of Medicine of the Valencian Community, Spain
| | - Luis Franco
- Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain,Royal Academy of Medicine of the Valencian Community, Spain,Institute for Health Research of the University Clinic Hospital (INCLIVA), Spain,Spanish Royal Academy of Sciences, Spain
| | - Gerardo López-Rodas
- Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain,Royal Academy of Medicine of the Valencian Community, Spain,Institute for Health Research of the University Clinic Hospital (INCLIVA), Spain
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Wang M, Phadke M, Packard D, Yadav D, Gorelick F. Zinc: Roles in pancreatic physiology and disease. Pancreatology 2020; 20:1413-1420. [PMID: 32917512 PMCID: PMC7572834 DOI: 10.1016/j.pan.2020.08.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/23/2020] [Accepted: 08/25/2020] [Indexed: 12/11/2022]
Abstract
Zinc is an essential trace element. Deficiencies are frequently seen with gastrointestinal diseases, including chronic pancreatitis, nutritional deficiency, and reduced intestinal absorption. Additionally, reduced zinc levels have been linked to cellular changes associated with acute pancreatitis such as enhanced inflammation with increased macrophage activation and production of inflammatory cytokines such as IL-1β, impaired autophagy, and modulation of calcium homeostasis. Preliminary data suggest that zinc deficiency may lead to pancreatic injury in animal models. The purpose of this review is to explore the biologic effects of zinc deficiency that could impact pancreatic disease. MESH KEYWORDS: Malnutrition, inflammation, trace element.
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Affiliation(s)
- Melinda Wang
- Yale School of Medicine, Department of Internal Medicine and VA HealthCare System, CT, USA
| | - Madhura Phadke
- Yale School of Medicine, Department of Internal Medicine and VA HealthCare System, CT, USA
| | - Daniel Packard
- Yale School of Medicine, Department of Internal Medicine and VA HealthCare System, CT, USA
| | - Dhiraj Yadav
- University of Pittsburgh, Department of Medicine, USA
| | - Fred Gorelick
- Yale School of Medicine, Department of Internal Medicine and VA HealthCare System, CT, USA.
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Kuzi S, Mazaki-Tovi M, Suchodolski JS, Rimer D, Lidbury JA, Steiner JM, Buono A, Nivy R, Segev G, Aroch I. Protease inhibitors, inflammatory markers, and their association with outcome in dogs with naturally occurring acute pancreatitis. J Vet Intern Med 2020; 34:1801-1812. [PMID: 32893923 PMCID: PMC7517856 DOI: 10.1111/jvim.15895] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 08/15/2020] [Accepted: 08/19/2020] [Indexed: 12/13/2022] Open
Abstract
Background Acute pancreatitis (AP) presumably is associated with pancreatic protease activation, protease inhibitor (PI) depletion, and inflammatory mediator secretion. Objectives Examine PIs and inflammatory mediator concentrations in dogs with AP and their association with death. Animals Thirty‐one dogs diagnosed with AP based on clinical signs, ultrasonographic findings, and increased canine pancreatic lipase immunoreactivity (cPLI) and 51 healthy control dogs. Methods Antithrombin and α2‐antiplasmin activity (ATA and α2AP, respectively) and concentrations of α1‐proteinase inhibitor (α1PI), α2‐macroglobulin (α2MG), C‐reactive protein (CRP), interleukins (ILs)‐2,6,8 and tumor necrosis factor‐α (TNF‐α) were prospectively measured. Severity of AP was assessed by clinical severity scoring systems. Results Mortality rate was 19%. Antithrombin activity was lower (P = .004) and maximal CRP, IL‐6, and TNF‐α concentrations higher (P < .04) in the AP group compared to the controls, whereas IL‐2, IL‐8, α1PI, and α2AP concentrations did not differ between groups. Serum α2MG concentration was not reliably detected. Serum cPLI, CRP, and IL‐6 concentrations were significantly and positively correlated. The ATA was lower (P = .04), and canine acute pancreatitis severity (CAPS) scores higher (P = .009) in nonsurvivors compared to survivors. Higher CAPS scores were associated (P < .05) with decreased ATA and increased cPLI, CRP, and IL‐6 concentrations. Conclusions and Clinical Importance Systemic inflammation in dogs with AP is manifested by increased inflammatory mediator concentrations, correlating with cPLI and CRP concentrations. Hypoantithrombinemia is associated with death. Serum concentrations of α2AP and α1PI are less useful prognostic markers. The CAPS score is a useful prognostic marker in dogs with AP.
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Affiliation(s)
- Sharon Kuzi
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Michal Mazaki-Tovi
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Dar Rimer
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Jonathan A Lidbury
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Joerg M Steiner
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Agostino Buono
- Gastrointestinal Laboratory, Texas A&M University, College Station, Texas, USA
| | - Ran Nivy
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Gilad Segev
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
| | - Itamar Aroch
- Department of Small Animal Internal Medicine, The Hebrew University Veterinary Teaching Hospital and Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel
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40
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Shin JY, Choi JW, Kim DG, Zhou ZQ, Shin YK, Seo JH, Song HJ, Choi BM, Bae GS, Park SJ. Protective effects of Coenzyme Q10 against acute pancreatitis. Int Immunopharmacol 2020; 88:106900. [PMID: 32829089 DOI: 10.1016/j.intimp.2020.106900] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 08/05/2020] [Accepted: 08/12/2020] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis (AP) refers to inflammation in the pancreas, which may lead to death in severe cases. Coenzyme Q10 (Q10), generally known to generate energy, plays an important role as an anti-oxidant and anti-inflammatory effector. Here, we showed the effect of Q10 on inflammatory response in murine AP model. For this study, we induced AP by injection of cerulein intraperitoneally or pancreatic duct ligation (PDL) in mice. The level of cytokines and digestive enzymes were measured in pancreas, and blood. All pancreatic tissues were excised for investigation such as histological changes, infiltration of immune cells. Administration of Q10 attenuated the severity of AP and its associated pulmonary complication as shown by reduction of acinar cell death, parenchymal edema, inflammatory cell infiltration and alveolar thickening in both cerulein-induced AP and PDL-induced AP. Moreover, reduction of the cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were observed in pancreas and pancreatic acinar cells by Q10. Furthermore, Q10 reduced the infiltration of immune cells such as monocytes and neutrophils and augmentation of chemokines such as CC chemokine-2 (CCL2) and C-X-C chemokine-2 (CXCL2) in pancreas of AP mice. In addition, Q10 deactivates the phosphorylation of extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) in pancreas. In conclusion, these observations suggest that Q10 could attenuate the pancreatic damage and its associated pulmonary complications via inhibition of inflammatory cytokines and inflammatory cell infiltration and that the deactivation of ERK and JNK by Q10 might contribute to the attenuation of AP.
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Affiliation(s)
- Joon Yeon Shin
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Ji-Won Choi
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Dong-Gu Kim
- Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Zi Qi Zhou
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Yong Kook Shin
- Department of Bio Pharmaceutical Industry, Semyung University, Semyeong-ro 65, Jecheon, Chungcheongbuk-do 27136, Republic of Korea
| | - Jae Ho Seo
- Department of Biochemistry, School of Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Ho-Joon Song
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea
| | - Byung-Min Choi
- Department of Biochemistry, School of Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea.
| | - Gi-Sang Bae
- Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Department of Pharmacology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Research Center of Traditional Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea.
| | - Sung-Joo Park
- Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea; Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan-daero 460, Iksan, Jeollabuk-do 54538, Republic of Korea.
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41
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El Morsy EM, Ahmed MA. Carvedilol attenuates l-arginine induced acute pancreatitis in rats through modulation of oxidative stress and inflammatory mediators. Chem Biol Interact 2020; 327:109181. [DOI: 10.1016/j.cbi.2020.109181] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 05/29/2020] [Accepted: 06/15/2020] [Indexed: 12/18/2022]
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Xiao J, Huang K, Lin H, Xia Z, Zhang J, Li D, Jin J. Mogroside II E Inhibits Digestive Enzymes via Suppression of Interleukin 9/Interleukin 9 Receptor Signalling in Acute Pancreatitis. Front Pharmacol 2020; 11:859. [PMID: 32587518 PMCID: PMC7298197 DOI: 10.3389/fphar.2020.00859] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/26/2020] [Indexed: 12/20/2022] Open
Abstract
The incidence of pancreatitis (AP) is increasing and there is no specific treatment available. Intracellular digestive enzyme activation is a key event in the pathogenesis of AP downstream of cytosolic calcium overload and impaired autophagy. Siraitia grosvenorii (Swingle) was used in Traditional Chinese Medicine to reduce inflammation and facilitate bowel movement. The bioactive components of this plant show hypolipedimic, antidiabetic, antifibrotic activity and have been used against pancreatic cancer. Here, we examined whether mogroside IIE, a major bioactive component of unripe S. grosvenorii fruit, can protect against AP. We found that mogroside IIE decreased the activity of trypsin and cathepsin B induced by cerulein plus lipopolysaccharide (LPS) in the pancreatic acinar cell line AR42J and primary acinar cells in a dose- and time-dependent manner. Mogroside IIE treatment decreased the levels of serum lipase and serum amylase in mice injected with cerulein plus LPS without influencing inflammation significantly. A multi-cytokine array revealed that mogroside IIE decreased the level of interleukin 9 (IL-9) in AP mice. Exogenous IL-9 eliminated the mogroside IIE induced reduction of trypsin and cathepsin B activity and reversed the inhibition of cytosolic calcium and modulation of autophagy mediated by mogroside IIE. An IL-9 receptor antibody neutralized the effect of IL-9, restoring mogroside IIE activity. The mogroside IIE targeted IL-9 may partially arise from Th9 cells. Taken together, we provide experimental evidence that mogroside IIE ameliorates AP in cell models and mice through downregulation of the IL-9/IL-9 receptor pathway.
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Affiliation(s)
- Juan Xiao
- Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin, China.,China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, China.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, China
| | - Kai Huang
- Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Houmin Lin
- Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Zhijia Xia
- Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Jing Zhang
- Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Dianpeng Li
- Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, Guilin, China
| | - Junfei Jin
- Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin, China.,China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, China.,Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, China.,Guangxi Key Laboratory of Sphingolipid Metabolism (Incubated), Guilin Medical University, Guilin, China
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Zhu C, Liu Y, Song Y, Wang Q, Liu Y, Yang S, Li D, Zhang Y, Cheng B. Deletion of macrophage migration inhibitory factor ameliorates inflammation in mice model severe acute pancreatitis. Biomed Pharmacother 2020; 125:109919. [PMID: 32062385 DOI: 10.1016/j.biopha.2020.109919] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 12/15/2019] [Accepted: 12/21/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine implicated in sepsis, rheumatoid arthritis and other diseases. However, the role of MIF in acute pancreatitis (AP) remains unclear. This study aims to explore the role of MIF in the pathogenesis of AP using MIF-/- mice (referred to as KO) and the biological effects of pharmacological inhibition of MIF in l-arginine induced AP. METHODS AP was induced in C57BL/6 wild-type (referred to as WT) and KO mice by administration of l-arginine. The severity of AP was assessed by serum analysis of amylase and lipase, and of these pro-inflammatory cytokines TNF-α and IL-1β. Histological hematoxylin and eosin (H&E) and immunohistochemical staining of pancreatic tissues were examined for inflammation and expression of pro-inflammatory mediators. We also investigated the biological effects of pharmacological inhibition of MIF activity using ISO-1((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester). RESULTS At 72 h after the induction of AP with l-arginine, significantly lower levels of serum amylase, lipase, TNF-α, and IL-1β were observed in KO mice when compared with WT controls. Histological examination further showed protective effects against pancreatic tissue damage and inflammation, with pancreatic expression of TNF-α, IL-1β and NF-κB p65 markedly reduced. Pharmacological inhibition of MIF activity with ISO-1 markedly mirrored the protective effect seen in the KO AP model providing further evidence that MIF is involved in the pathogenesis of AP. CONCLUSION Our data provided strong evidence for the participation of MIF in the pathogenesis of AP and subsequent inflammatory response. The genetic ablation of MIF or its inhibition with pharmacological agents significantly ameliorated the severity of AP.
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Affiliation(s)
- Changju Zhu
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China.
| | - Yanna Liu
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China
| | - Yaodong Song
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China
| | - Qiaofang Wang
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China
| | - Yanyan Liu
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China
| | - Shujun Yang
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China
| | - Dejian Li
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, China
| | - Yan Zhang
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China
| | - Bo Cheng
- Department of Emergency, The First Affiliated Hospital of Zhengzhou University, No 1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China
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Yu S, Yao D, Liang X, Jin K, Fu Y, Liu D, Zhang L, Yang J, Song X, Xu J, Yu X. Effects of different triglyceride-lowering therapies in patients with hypertriglyceridemia-induced acute pancreatitis. Exp Ther Med 2020; 19:2427-2432. [PMID: 32256719 PMCID: PMC7086183 DOI: 10.3892/etm.2020.8501] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 09/10/2019] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to investigate the effects of various triglyceride (TG)-lowering therapies on hypertriglyceridemia-induced acute pancreatitis (HTGAP). A total of 132 patients with HTGAP were retrospectively divided into an insulin intensive therapy (IIT), a plasma exchange (PE) and a non-intensive insulin therapy (NIIT) group according to the TG-lowering therapies they had received. The clinical and biochemical data of the subjects were analyzed. The baseline data, including sex, age, TG, amylase, severe acute pancreatitis and systemic inflammatory response syndrome were not significantly different among the three groups (P>0.05). The 24-h TG clearance rate (χ2=7.74, P=0.021), onset to treatment time (χ2=14.50, P<0.001) and the time required to reach the target TG level (χ2=6.12, P=0.047) were different in these three groups, but no significant differences were observed between the IIT and NIIT groups (P>0.05). The incidence of therapy-associated complications in the PE group (30.23%) was higher than that in the IIT (2.17%) and NIIT (4.65%) groups. The difference in the incidence of therapy-associated complications was significant among the three groups (P<0.001), but no significant difference was present between the IIT and NIIT groups (P>0.05). In the PE group, the length of stay was increased compared with that in the IIT and NIIT groups (χ2=7.05, P<0.05), while there was no significant difference between the IIT and NIIT groups (P>0.05). The present study suggested that NIIT at presentation had a similar therapeutic efficacy to that of IIT to improve the prognosis of HTGAP, and NIIT and IIT were associated with fewer complications than PE treatment. NIIT may favorably perform in patients presenting early after symptom onset and may be considered for clinical application.
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Affiliation(s)
- Shanshan Yu
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Dongqi Yao
- Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
| | - Xianquan Liang
- Department of Emergency, The Second People's Hospital of Guiyang, Guiyang, Guizhou 550023, P.R. China
| | - Kui Jin
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Yangyang Fu
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Danyu Liu
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Lili Zhang
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Jing Yang
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Xiao Song
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Jun Xu
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
| | - Xuezhong Yu
- Department of Emergency, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China
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Charalabopoulos A, Davakis S, Lambropoulou M, Papalois A, Simopoulos C, Tsaroucha A. Apigenin Exerts Anti-inflammatory Effects in an Experimental Model of Acute Pancreatitis by Down-regulating TNF-α. In Vivo 2019; 33:1133-1141. [PMID: 31280202 DOI: 10.21873/invivo.11583] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Revised: 06/06/2019] [Accepted: 06/10/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND/AIM This study investigated the anti-inflammatory effect of apigenin in an experimental model of acute pancreatitis. Inflammatory response was reflected by tissue expression of the cytokine TNF-α coupled with histological examination. MATERIALS AND METHODS Wistar rats were divided into three groups: Sham-group animals underwent laparotomy only, without any other interventions. Control-group animals underwent laparotomy and bilio-pancreatic duct ligation to induce pancreatitis without apigenin administration. Apigenin group animals were further treated with apigenin. Euthanasia was performed at 6, 12, 24, 48 and 72 h post-operatively. RESULTS Over-expression of TNF-α in relation to postoperative time was observed in the control group (p<0.001). In the apigenin group, under-expression of TNF-α in relation to postoperative time was observed (p<0.013). At 72 h, apigenin reduced pancreatic TNF-α expression and prevented pancreatic necrosis. CONCLUSION Apigenin slows progression and reduces severity of acute pancreatitis. Apigenin may serve as an adjunct to a more successful therapeutic strategy in acute pancreatitis.
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Affiliation(s)
- Alexandros Charalabopoulos
- Department of Upper Gastrointestinal and General Surgery, Broomfield Hospital, Mid Essex Hospital Services NHS Trust, Essex, U.K.,Experimental-Research Center, ELPEN Pharmaceuticals, Athens, Greece
| | - Spyridon Davakis
- Department of Upper Gastrointestinal and General Surgery, Broomfield Hospital, Mid Essex Hospital Services NHS Trust, Essex, U.K. .,First Department of Surgery, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Lambropoulou
- Department of Histopathology, Faculty of Medicine, Democritus University of Thrace, Alexandroupoli, Greece
| | | | - Constantinos Simopoulos
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, Alexandroupoli, Greece
| | - Alexandra Tsaroucha
- Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, Alexandroupoli, Greece
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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: 12] [Impact Index Per Article: 2.0] [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.
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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.
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Lin Y, He S, Gong J, Ding X, Liu Z, Gong J, Zeng Z, Cheng Y. Continuous veno-venous hemofiltration for severe acute pancreatitis. Cochrane Database Syst Rev 2019; 10:CD012959. [PMID: 31618443 PMCID: PMC6953293 DOI: 10.1002/14651858.cd012959.pub2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Severe acute pancreatitis is associated with high rates of mortality and life-threatening complications. Continuous veno-venous hemofiltration (CVVH) has been used in some centers to reduce mortality and avoid local or systemic complications, however its efficiency and safety is uncertain. OBJECTIVES To assess the benefits and harms of CVVH in patients suffering from severe acute pancreatitis; to compare the effects of different CVVH techniques; and to evaluate the optimal time for delivery of CVVH. SEARCH METHODS We searched the Cochrane Library (2019, Issue 8), MEDLINE (1946 to 13 September 2019), Embase (1974 to 13 September 2019), and Science Citation Index Expanded (1982 to 13 September 2019). SELECTION CRITERIA We included all randomized controlled trials (RCTs) that compared CVVH versus no CVVH in participants with severe acute pancreatitis. We also included RCTs that compared different types of CVVH and different schedules for CVVH in participants with severe acute pancreatitis. DATA COLLECTION AND ANALYSIS Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes, and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS We included two studies, involving a total of 94 participants, in the review.Continuous veno-venous hemofiltration versus no interventionWe included one study in which 64 participants with severe acute pancreatitis were randomized to undergo CVVH (32 participants) or no intervention (32 participants). There were no deaths in either group (very low-quality evidence). Adverse events, length of stay in the intensive care unit (ICU), length of hospital stay, total hospital cost, and quality of life were not reported in the study.One type of continuous veno-venous hemofiltration versus a different type of continuous veno-venous hemofiltrationWe included one study in which 30 participants with severe acute pancreatitis were randomized to undergo high-volume CVVH (15 participants) or standard CVVH (15 participants). High-volume CVVH may lead to little or no difference in in-hospital mortality rates (20.0% in the high-volume CVVH group versus 33.3% in the standard CVVH group; risk ratio (RR) 0.60, 95% confidence interval (CI) 0.17 to 2.07; 30 participants; 1 study; low-quality evidence). We are uncertain whether high-volume hemofiltration reduces rates of adverse events (13.3% in both groups; RR 1.00, 95% CI 0.16 to 6.20; 30 participants; 1 study; very low-quality evidence). Length of ICU stay, length of hospital stay, total hospital cost, and quality of life were not reported in the study. AUTHORS' CONCLUSIONS The quality of the current evidence is very low or low. For both comparisons addressed in this review, data are sparse. It is unclear whether CVVH has any effect on mortality or complications in patients with severe acute pancreatitis. It is also unclear whether high-volume CVVH is superior, equivalent or inferior to standard CVVH in patients with severe acute pancreatitis.
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Affiliation(s)
- Yanjun Lin
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, No. 74, Lin Jiang Road, Chongqing, China, 400010
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Rodriguez-Nicolas A, Jiménez P, Carmona FD, Martín J, Matas Cobos AM, Ruiz-Cabello F, Redondo-Cerezo E. Association between Genetic Polymorphisms of Inflammatory Response Genes and Acute Pancreatitis. Immunol Invest 2019; 48:585-596. [PMID: 31044631 DOI: 10.1080/08820139.2019.1576729] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Inflammation plays a central role in the pathophysiology of acute pancreatitis (AP). We hypothesized that changes in the function of key components of the inflammatory cascade, caused by genetic polymorphisms, could determine the development and/or severity of AP. We studied the following polymorphisms in 269 patients: IL23R rs11209026, TNF rs1800629, RIPK2 rs42490, NOD2 rs9302752, MCP1 rs1024611 and NFKB1 rs28362491. The rs11209026 A allele was related to the presence of AP (p = 0.007261; OR = 1 .523). Epistasis analysis revealed that AP susceptibility was increased by interaction between IL23R rs11209026 and TNF rs1800629 (p = 1.205 × 10-5; ORinteraction = 4.031). The rs42490-G allele was associated with an increased risk of severe pancreatitis (p = 0.01583; OR = 2.736), severe or moderately severe pancreatitis (p = 0.04206; OR = 1.609), and death (p = 0.03226; OR = 3.010). In conclusion, these results point to a plausible role for genetic polymorphisms in IL23R and RIPK2 in the development and severity of AP.
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Affiliation(s)
- Antonio Rodriguez-Nicolas
- a Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico , Hospital Universitario Virgen de las Nieves , Granada , Spain
- b Programa de doctorado en Biomedicina , Universidad de Granada , Granada , Spain
| | - Pilar Jiménez
- a Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico , Hospital Universitario Virgen de las Nieves , Granada , Spain
| | - F David Carmona
- c Departamento de Genética e Instituto de Biotecnología , Universidad de Granada , Granada , Spain
| | - Javier Martín
- d Instituto de Parasitología y Biomedicina López Neyra , CSIC , Granada , Spain
| | - Ana M Matas Cobos
- e Servicio de Aparato Digestivo , Hospital Universitario Virgen de las Nieves , Granada , Spain
| | - Francisco Ruiz-Cabello
- a Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico , Hospital Universitario Virgen de las Nieves , Granada , Spain
- f Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA) , Granada , Spain
| | - Eduardo Redondo-Cerezo
- e Servicio de Aparato Digestivo , Hospital Universitario Virgen de las Nieves , Granada , Spain
- f Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA) , Granada , Spain
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Arutla M, Raghunath M, Deepika G, Jakkampudi A, Murthy HVV, Rao GV, Reddy DN, Talukdar R. Efficacy of enteral glutamine supplementation in patients with severe and predicted severe acute pancreatitis- A randomized controlled trial. Indian J Gastroenterol 2019; 38:338-347. [PMID: 31612309 DOI: 10.1007/s12664-019-00962-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 05/14/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND In severe acute pancreatitis (AP), intravenous glutamine has been shown to reduce the rate of complications, hospital stay, and mortality. In the present randomized trial, we aimed to evaluate the effect of enteral glutamine supplementation on clinical outcomes, gut permeability, systemic inflammation, oxidative stress, and plasma glutamine levels in patients with severe and predicted severe AP. METHODS Patients with AP admitted within 72 h of onset of symptoms were included. The primary outcome measure was development of infected pancreatic and peri-pancreatic necrosis and in-hospital mortality. High-sensitivity C-reactive protein (HS-CRP) and interleukin-6 (IL-6) were evaluated as markers of inflammation; plasma thiobarbituric acid reactive substances (TBARS) and activities of serum superoxide dismutase and glutathione peroxidase were determined to evaluate oxidative stress; serum polyethylene glycol (PEG) was tested for intestinal permeability; subjective global assessment (SGA) was used for nutritional assessment, and an improvement in organ function was measured by the Modified Marshall score. Intention-to-treat analysis was used. A p-value of < 0.05 was considered statistically significant. RESULTS After power calculation, we enrolled 18 patients in the glutamine and 22 in the control arm. There was no significant improvement in the development of infected necrosis and in-hospital mortality between the groups. Improvement in Modified Marshall score was observed in a higher proportion of patients receiving glutamine (15 [83.3%] vs. 12 [54.5%]; p = 0.05). Plasma glutamine levels improved more in glutamine-treated group (432.72 ± 307.83 vs. 618.06 ± 543.29 μM/L; p = 0.004), while it was lower in controls (576.90 ± 477.97 vs. 528.20 ± 410.45 μM/L; p = 0.003). PEG level was lower after glutamine supplementation (39.91 ± 11.97 vs. 32.30 ± 7.39 ng/mL; p = 0.02). Statistically significant reduction in IL-6 concentration was observed in the glutamine group at the end of treatment (87.44 ± 7.1 vs. 63.42 ± 33.7 μM/L; p = 0.02). CONCLUSIONS Despite absence of improvement in infected necrosis and in-hospital mortality, enteral glutamine supplementation showed improvement in gut permeability, oxidative stress, and a trend towards improvement in organ function as depicted by improvement in the Modified Marshall score. TRIAL REGISTRATION NCT01503320.
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Affiliation(s)
- Madhulika Arutla
- Department of Clinical Nutrition, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India
| | - M Raghunath
- Department of Endocrinology and Metabolism, National Institute of Nutrition, Near Tarnaka, Jamai-Osmania, Hyderabad, 500 007, India
| | - G Deepika
- Department of Biochemistry, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India
| | - Aparna Jakkampudi
- Wellcome DBT Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, 500 082, India
| | - H V V Murthy
- Department of Biostatistics, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India
| | - G V Rao
- Department of Surgical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India
| | - D Nageshwar Reddy
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India
| | - Rupjyoti Talukdar
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India. .,Pancreas Clinic, Pancreas Research Group, Asian Healthcare Foundation, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India.
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50
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Gulla A, Gulbinas A, Dambrauskas Z, Strupas K. Heme Oxygenase-1 Polymorphism Is Associated With the Development of Necrotic Acute Pancreatitis Via Vascular Cell Adhesion Molecule-1 and the E-Selectin Expression Regulation Pathway. Pancreas 2019; 48:787-791. [PMID: 31210657 DOI: 10.1097/mpa.0000000000001328] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Severe acute pancreatitis can lead to systemic complications. Here, we explore the mechanisms based on our previous study associated with the deregulation of heme oxygenase-1 (HO-1) and development of severe acute pancreatitis. METHODS Acute pancreatitis patients (n = 135) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed with an ABI 3130 genetic analyzer and GeneMapper software. A short allele was defined ≤27 dinucleotide (GT) repeats, whereas a long allele was defined >27 GT. Levels of 12 different cytokines in blood serum were measured by enzyme-linked immunosorbent assay. All samples in this study were consistently stored in -80°C. RESULTS Patients with the long long genotype expressed E-selectin and vascular cell adhesion molecule-1 at statistically significantly higher levels in serum compared with short short genotype or short long genotypes. Vascular cell adhesion molecule-1 and E-selectin serum levels significantly correlate with the total allele length of the HO-1 promoter region. CONCLUSION Polymorphism of the GT repeats in the HO-1 promoter region may be a risk factor for developing acute necrotizing pancreatitis due to deregulation of the immune response.
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Affiliation(s)
| | - Antanas Gulbinas
- Department of Surgery, Hospital of Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Zilvinas Dambrauskas
- Department of Surgery, Hospital of Lithuanian University of Health Sciences, Kaunas, Lithuania
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