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Clinical Significance of Serum Nitric Oxide, Urine Nitric Oxide, and Urinary Nitric Oxide-to-Creatinine Ratio in Acute Pancreatitis. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03580-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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Shi Z, Ye W, Zhang J, Zhang F, Yu D, Yu H, Chen B, Zhou M, Sun H. LipoxinA4 attenuates acute pancreatitis-associated acute lung injury by regulating AQP-5 and MMP-9 expression, anti-apoptosis and PKC/SSeCKS-mediated F-actin activation. Mol Immunol 2018; 103:78-88. [PMID: 30219663 DOI: 10.1016/j.molimm.2018.09.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Revised: 07/20/2018] [Accepted: 09/04/2018] [Indexed: 11/29/2022]
Abstract
An essential component of acute pancreatitis(AP)-induced acute lung injury(ALI) is the inflammation that is part of the body's systemic inflammatory response to a variety of systemic stimuli. Lipoxins(LXs) are considered important endogenous lipids that mediate the resolution of inflammation. In previous studies, we found that Lipoxin A4 (LXA4) reduced AP-induced pulmonary oedema and TNF-α production in lung. However, the underlying mechanism remains unclear. Due to the above studies, we investigated the aquaporin, matrix metalloprotein, apoptosis and PKC/SSeCKS signal pathway in cellular and animal models of AP-associated lung injury following LXA4 intervention. In this study, we first proved LXA4 could effectively promote F-actin reconstruction and regulate its expression in pulmonary microvascular endothelial cells both in vivo and vitro via suppressing PKC/SSeCKS signalling pathway. Next, we found that LXA4 attenuated cell growth inhibition and apoptosis in lung tissues of AP-ALI mice and HPMECs. Additionally, we demonstrated that LXA4 could regulate the expression of AQP-5 and MMP-9 to stabilize the permeability of pulmonary microvascular endothelial cell. In summary, our results suggest that the anti-inflammatory eff ;ects of LXA4 may be due to the inhibition of both the PKC/SSeCKS pathway and apoptosis to reduce alveolar fluid exudation and to the regulation of AQP-5 and MMP-9 expression to maintain the clearance of alveolar fluid. Thus, LXA4 is capable of exerting protective eff ;ects on AP-induced ALI.
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Affiliation(s)
- Zhehao Shi
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China
| | - Wen Ye
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China
| | - Jiecheng Zhang
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China
| | - Fan Zhang
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China
| | - Dinglai Yu
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China
| | - Huajun Yu
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China
| | - Bicheng Chen
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, People's Republic of China
| | - Mengtao Zhou
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China; Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, People's Republic of China.
| | - Hongwei Sun
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.
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Zaman A, Bivona TG. Emerging application of genomics-guided therapeutics in personalized lung cancer treatment. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:160. [PMID: 29911108 DOI: 10.21037/atm.2018.05.02] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
In lung cancer, genomics-driven comprehensive molecular profiling has identified novel chemically and immunologically addressable vulnerabilities, resulting in an increasing application of precision medicine by targeted inactivation of tumor oncogenes and immunogenic activation of host anti-tumor surveillance as modes of treatment. However, initially profound response of these targeted therapies is followed by relapse due to therapy-resistant residual disease states. Although distinct mechanisms and frameworks for therapy resistance have been proposed, accounting for and upfront prediction of resistance trajectories has been challenging. In this review, we discuss in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the current standing, and challenges associated with genomics-guided strategies for personalized therapy against both oncogenic alterations as well as post-therapy resistance mechanisms. In NSCLC, we catalog the targeted therapy approaches against most notable oncogenic alterations such as epidermal growth factor receptor (EGFR), serine/threonine-protein kinase b-raf (BRAF), Kirsten rat sarcoma viral proto-oncogene (KRAS), anaplastic lymphoma kinase (ALK), ROS1 proto-oncogene receptor tyrosine kinase (ROS1). For SCLC, currently highly recalcitrant to targeted therapy, we enumerate a range of exciting and maturing precision medicine approaches. Furthermore, we discuss a number of immunotherapy approaches, in combination or alone, that are being actively pursued clinically in lung cancer. This review not only highlights common mechanistic themes underpinning different classes of resistance and discusses tumor heterogeneity as a source of residual disease, but also discusses potential ways to overcome these barriers. We emphasize how an extensive understanding of these themes can predict and improve therapeutic strategies, such as through poly-therapy approaches, to forestall tumor evolution upfront.
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Affiliation(s)
- Aubhishek Zaman
- Department of Medicine, University of California, San Francisco, CA, USA.,UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USA
| | - Trever G Bivona
- Department of Medicine, University of California, San Francisco, CA, USA.,UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USA
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Is MicroRNA-127 a Novel Biomarker for Acute Pancreatitis with Lung Injury? DISEASE MARKERS 2017; 2017:1204295. [PMID: 29434409 PMCID: PMC5757136 DOI: 10.1155/2017/1204295] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 09/23/2017] [Accepted: 10/15/2017] [Indexed: 02/05/2023]
Abstract
Background and Aims The aim of this study was to determine the expression of microRNA-127 (miR-127) in both rat models and patients of acute pancreatitis (AP) with lung injury (LI). Methods Rats were administrated with retrograde cholangiopancreatography injection of 0.5% or 3.5% sodium taurocholate to induce AP with mild or severe LI and were sacrificed at 6, 12, and 24 h. Rats from the control group received a laparotomy only. Plasma from a prospective cohort of AP patients was collected. The levels of miR-127 in the tissues and plasma were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results The upregulation of miR-127 in the lungs of rats was detected in the groups of AP with severe LI at 6 h and 24 h, whereas it was scarcely detectable in plasma. In the pilot study that included 18 AP patients and 5 healthy volunteers, the plasma miR-127 level was significantly downregulated in AP patients with respiratory failure compared with the healthy volunteers (P = 0.014) and those without respiratory failure (P = 0.043). Conclusion miR-127 might serve as a potential marker for the identification of AP with LI.
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Jin Y, Liu L, Chen B, Bai Y, Zhang F, Li Q, Lv C, Sun H, Li J, Rubby S, Yang L, Andersson R, Zhou M. Involvement of the PI3K/Akt/NF- κB Signaling Pathway in the Attenuation of Severe Acute Pancreatitis-Associated Acute Lung Injury by Sedum sarmentosum Bunge Extract. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9698410. [PMID: 29359164 PMCID: PMC5735615 DOI: 10.1155/2017/9698410] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 09/19/2017] [Accepted: 10/22/2017] [Indexed: 01/22/2023]
Abstract
Sedum sarmentosum Bunge possesses excellent anti-inflammatory properties and was used in the treatment of inflammatory diseases. The aim of the present study was to investigate the efficiency of Sedum sarmentosum Bunge extract (SSBE) on severe acute pancreatitis-associated (SAP-associated) acute lung injury (ALI) in rats and to explore the underlying mechanisms. Here, we used a sodium taurocholate-induced SAP rat model to determine the role of SSBE in ALI. During the course of pancreatitis, the expressions of phosphorylated phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt) and nuclear factor-kappa B (NF-κB) p65 in the lungs were upregulated. Meanwhile, a parallel increase in the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the lungs was observed after the induction of SAP. Treatment with SSBE significantly reduced the expression of p-Akt and p-p65 in the lungs and attenuated the severity of SAP-associated ALI compared to the SAP group at 12 h and 24 h. In summary, this study showed that SSBE has beneficial effects on SAP-associated ALI, probably through the PI3-K/Akt signaling pathways by suppressing the NF-κB activities.
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Affiliation(s)
- Yuepeng Jin
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Lewei Liu
- YueQing Affiliated Hospital of Wenzhou Medical University, YueQing People's Hospital, Yueqing, Zhejiang Province, China
| | - Bicheng Chen
- Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Yongyu Bai
- Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Fan Zhang
- Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Qiang Li
- Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Chongqing Lv
- Shengli Oilfield Central Hospital, Dongying, Shandong Province, China
| | - Hongwei Sun
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Junjian Li
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Sadman Rubby
- Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Lihong Yang
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Lund University and Lund University Hospital, Sweden
| | - Mengtao Zhou
- Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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Guibing R, Xiping Z, Xiaowen D, Dehong Z, Hongjiang Y, Xiaoru M, Wenju M, Xiangming H, Shuai Z. EFFECTS OF SALVIA MILTIORRHIZAE ON THE KIDNEY OF RATS WITH SEVERE ACUTE PANCREATITIS AND OBSTRUTIVE JAUNDICE. AFRICAN JOURNAL OF TRADITIONAL, COMPLEMENTARY, AND ALTERNATIVE MEDICINES : AJTCAM 2017; 14:103-124. [PMID: 28573227 PMCID: PMC5446434 DOI: 10.21010/ajtcam.v14i2.12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Background: Severe acute pancreatitis (SAP) and obstructive jaundice (OJ) are frequent recurring diseases that bring about huge threat to human health. Some reports have demonstrated that Salviae miltiorrhizae can protect multiple organs of SAP and OJ model animals or patients, but their related mechanisms were not clear. In this study, we observed the effects of Salvia miltiorrhizae injection on apoptosis and NF-κB expression in kidney and explored the protective effect and mechanism of Salvia miltiorrhizae on the kidney of SAP or OJ rats. The results obtained will provide a theoretical basis for clinical application of Salvia miltiorrhizae. Material and Methods: A total of 288 rats were used for SAP -and OJ-associated experiments. The mortality rates of rats, the contents of serum BUN and CREA, the expression levels of Bax, NF-κB proteins and the apoptosis index were observed, respectively. Results: The pathological changes in the kidney of SAP or OJ rats in treated group were mitigated to varying degrees. At 6 and 12 hours after operation in SAP rats or on 21 and 28 days after operation in OJ rats, the contents of serum CREA in treated group were significantly lower than those in model control group; At 3 and 6 hours after operation, the staining intensity of Bax protein of kidney in treated group was significantly lower than that in model control group; on 14 days after operation, the apoptosis index in the kidney of OJ rats in treated group was significantly lower than that in model control group. Conclusion: Salvia miltiorrhizae can exert protective effects on the kidney of SAP and OJ rats.
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Affiliation(s)
- Ren Guibing
- Department of Oncological Surgery, Affiliated Hospital, Logistics University of the Chinese People's Armed Police Force, Tianjin, 300162, PR China
| | - Zhang Xiping
- Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, PR China.,Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, PR China
| | - Ding Xiaowen
- Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, PR China
| | - Zou Dehong
- Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, PR China
| | - Yang Hongjiang
- Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, PR China
| | - Meng Xiaoru
- Department of Oncological Surgery, Affiliated Hospital, Logistics University of the Chinese People's Armed Police Force, Tianjin, 300162, PR China
| | - Mo Wenju
- Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, PR China
| | - He Xiangming
- Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, PR China
| | - Zhao Shuai
- Department of Breast Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, PR China
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Ateyya H, Wagih HM, El-Sherbeeny NA. Effect of tiron on remote organ injury in rats with severe acute pancreatitis induced by L-arginine. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:873-85. [PMID: 27118662 DOI: 10.1007/s00210-016-1250-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 04/19/2016] [Indexed: 12/11/2022]
Abstract
Acute pancreatitis (AP) is an acute inflammatory disorder of the pancreas that can be complicated by involvement of other remote organs. Oxidative stress is known to have a crucial role in the development of pancreatic acinar damage and one of the main causes in multisystem organ failure in experimental AP. The aim of the study was to determine the effect of tiron on pancreas and remote organ damage in L-arginine (L-Arg) induced AP rat model. Thirty-two male rats were divided in random into four groups: control, tiron, L-Arg, and tiron with L-Arg. At the end of the experiment, blood samples were withdrawn for biochemical analysis. The pancreas, lung, kidney, and liver were collected for histopathological examination. Estimation of pancreatic water content was done. Analysis of pulmonary, hepatic, renal, and pancreatic lipid peroxide levels (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) were carried out. Finally, nuclear factor kappa B (NF-κB) and transforming growth factor β1 (TGF-β1) expression in pancreatic tissue was determined. Results indicated that treatment with tiron significantly decreased lipid peroxide levels and markedly increased both SOD activity and GSH level. Moreover, histopathological analysis further confirmed that administration of tiron relatively ameliorates pancreatic acinar cells and remote organ damage. Increased immunoreactivity of NF-κB and TGF-β1 were reduced also by tiron treatment. These findings pointed out the protective role of the mitochondrial antioxidant, tiron against AP induced by L-Arg.
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Affiliation(s)
- Hayam Ateyya
- College of Pharmacy, Taibah University, El-Madinah, El-Munawarah, Saudi Arabia. .,Department of Clinical Pharmacology, Faculty of Medicine, Cairo University, Giza, Egypt.
| | - Heba M Wagih
- Medical Laboratories Technology Department, Faculty of Applied Medical Sciences, Taibah University, El-Madinah El-Munawarah, Saudi Arabia.,Pathology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Nagla A El-Sherbeeny
- College of Pharmacy, Taibah University, El-Madinah, El-Munawarah, Saudi Arabia.,Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
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Shamoon M, Deng Y, Chen YQ, Bhatia M, Sun J. Therapeutic implications of innate immune system in acute pancreatitis. Expert Opin Ther Targets 2015; 20:73-87. [PMID: 26565751 DOI: 10.1517/14728222.2015.1077227] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Acute pancreatitis (AP) is an inflammatory disorder of the pancreas encompassing a cascade of cellular and molecular events. It starts from premature activation of zymogens with the involvement of innate immune system to a potential systemic inflammatory response and multiple organ failure. Leukocytes are the major cell population that participate in the propagation of the disease. Current understanding of the course of AP is still far from complete, limiting treatment options mostly to conservative supportive care. Emerging evidence has pointed to modulation of the immune system for strategic therapeutic development, by mitigating the inflammatory response and severity of AP. In the current review, we have focused on the role of innate immunity in the condition and highlighted therapeutics targeting it for treatment of this challenging disease. AREAS COVERED The current review has aimed to elaborate in-depth understanding of specific roles of innate immune cells, derived mediators and inflammatory pathways that are involved in AP. Summarizing the recent therapeutics and approaches applied experimentally that target immune responses to attenuate AP. EXPERT OPINION The current state of knowledge on AP, limitations of presently available therapeutic approaches and the promise of therapeutic implications of innate immune system in AP are discussed.
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Affiliation(s)
- Muhammad Shamoon
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
| | - Yuanyuan Deng
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
| | - Yong Q Chen
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
| | - Madhav Bhatia
- b 2 University of Otago, Inflammation Research Group, Department of Pathology , Christchurch, 2 Riccarton Avenue, P.O. Box 4345, Christchurch 8140, New Zealand
| | - Jia Sun
- a 1 Jiangnan University, School of Food Science and Technology, The Synergetic Innovation Center of Food Safety and Nutrition, State Key Laboratory of Food Science and Technology , Wuxi, Jiangsu, China
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Tian XX, Wang BL, Cao YZ, Zhong YX, Tu YY, Xiao JB, He QF, Zhai LN. Comparison of protective effects of safflor injection and extract of Ginkgo biloba on lung ischemia/reperfusion injury in rabbits. Chin J Integr Med 2015; 21:229-233. [PMID: 24142260 DOI: 10.1007/s11655-013-1513-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2011] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To observe the protective effects of safflor Injection (SI) and extract of Ginkgo biloba (EGB) on lung ischemia-reperfusion injury (LIRI) and investigate its mechanism. METHODS In vivo rabbit model of LIRI was reconstructed. Forty rabbits were randomly and equally divided into four groups: sham-operation group (sham group), ischemia-reperfusion group (model group), ischemia-reperfusion plus SI group (safflor group) and ischemia-reperfusion plus EGB injection group (EGB group). Malondialdehyde (MDA) content, superoxide dismutase (SOD) and xanthine oxidase (XO) activity in serum were measured. The wet/dry weight ratio (W/D) of the lung tissue and activity of myeloperoxidase (MPO) were also tested. Ultrastructure change of the lung tissue was observed by the electron microscope. The expression of intercellular adhesion molecule-1 (ICAM-1) was measured by immunohistochemistry (IHC). RESULTS In the model group, MDA and XO increased and SOD decreased in serum compared with the sham group (P<0.01). The values of W/D, MPO and ICAM-1 of the model group were higher than those of the sham group (P<0.01), but those of the safflor group and EGB group were significantly lower than those of the model group (P<0.01). The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group (P<0.01). Compared with safflor group, in the EGB group MDA, XO, MPO decreased, SOD and ICAM-1 expression increased (P<0.05), but the change of W/D was not statistically significant (P>0.05). CONCLUSIONS SI and EGB may attenuate LIRI through antioxidation, inhibition of neutrophil aggregation and down-regulation of ICAM-1 expression. But EGB had more effect on the antioxidation, while SI did better on regulating ICAM-1 expression.
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Affiliation(s)
- Xiao-xi Tian
- Emergency Department, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China
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Thalidomide alleviates acute pancreatitis-associated lung injury via down-regulation of NFκB induced TNF-α. Pathol Res Pract 2014; 210:558-64. [DOI: 10.1016/j.prp.2014.04.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Revised: 04/21/2014] [Accepted: 04/29/2014] [Indexed: 12/20/2022]
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Matone J, Moretti AIS, Apodaca-Torrez FR, Goldenberg A. Ethyl-pyruvate reduces lung injury matrix metalloproteinases and cytokines and improves survival in experimental model of severe acute pancreatitis. Acta Cir Bras 2013; 28:559-67. [DOI: 10.1590/s0102-86502013000800002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2013] [Accepted: 07/22/2013] [Indexed: 01/14/2023] Open
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Akbarshahi H, Rosendahl AH, Westergren-Thorsson G, Andersson R. Acute lung injury in acute pancreatitis--awaiting the big leap. Respir Med 2012; 106:1199-1210. [PMID: 22749752 DOI: 10.1016/j.rmed.2012.06.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2011] [Revised: 05/09/2012] [Accepted: 06/01/2012] [Indexed: 12/12/2022]
Abstract
Acute lung injury is a severe complication to acute pancreatitis and a significant health problem associated with a considerable mortality. Underlying mechanisms are complex and poorly understood, although recent insights have identified several inflammatory profiles and cellular components involved to varying degrees during different phases of pancreatitis exacerbation and acute lung injury. This review aims to highlight the current understanding of the inflammatory and cellular components involved in and responsible for the associations of acute pancreatitis and acute lung injury, with the hope of thereby providing an increased understanding of the underlying mechanisms. In addition, novel experimental models of modulating the pancreatitis-associated acute lung injury are presented, interventions that may be of potential future clinical value.
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Affiliation(s)
- Hamid Akbarshahi
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund, Sweden
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You Z, Feng D, Xu H, Cheng M, Li Z, Kan M, Yao S. Nuclear factor-kappa B mediates one-lung ventilation-induced acute lung injury in rabbits. J INVEST SURG 2012; 25:78-85. [PMID: 22439834 DOI: 10.3109/08941939.2011.603817] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION Several studies have revealed the adverse effect of one-lung ventilation (OLV) on pulmonary function. Nuclear factor-kappa B (NF-κB) is a principal transcription factor of proinflammatory genes. This study was designed to investigate the role of NF-κB in OLV-mediated lung injury. METHODS Male rabbits, weighing 2.2 ± 0.3 kg, were randomly divided into five groups: sham tracheostomized (Sham), OLV (V(T) = 10 ml/kg, FiO(2) = 1.0), two-lung ventilation (TLV, V(T) = 10 ml/kg, FiO(2) = 1.0), OLV preceded by the treatment with NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC, 50 mg/kg, i.v.), and TLV with the PDTC pretreatment. Arterial blood gases, lung pathological changes, and production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-8) were assessed. NF-κB activation was determined by electrophoretic mobility shift assay (EMSA) and western blotting of nuclear NF-κB p65. RESULTS The OLV significantly decreased the ratio of partial pressure of oxygen and fraction inspired oxygen (PaO(2)/FiO(2)) compared to the Sham group (p < .01). However, the TLV had no evident effect on the PaO(2)/FiO(2) ratio. The pretreatment with PDTC significantly reversed the OLV-induced reduction in the PaO(2)/FiO(2) ratio. The PDTC pretreatment also markedly attenuated the OLV-mediated lung injury and proinflammatory cytokine production. The OLV potentiated the NF-κB DNA binding activity assessed by EMSA and the NF-κB nuclear translocation. The OLV-mediated NF-κB activation was markedly inhibited by the PDTC pretreatment. CONCLUSION Our data collectively demonstrate that OLV can cause lung injury through the activation of NF-κB and the production of proinflammatory cytokines. Blocking NF-κB reduces lung inflammation and may be an effective strategy in the management of OLV-induced lung damage.
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Affiliation(s)
- Zhijian You
- Department of Anesthesiology, First Affiliated Hospital of Shantou University Medical College, Shantou, China.
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Lin CC, Hsieh NK, Liou HL, Chen HI. Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs. J Biomed Sci 2012; 19:27. [PMID: 22375599 PMCID: PMC3311060 DOI: 10.1186/1423-0127-19-27] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2011] [Accepted: 03/01/2012] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes. METHODS The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 μg/g), PMA 4 μg/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined. RESULTS PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. CONCLUSIONS Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative effect on the PMA-induced ALI. NAC exerts protective effects on the inflammatory cascade leading to pulmonary injury. This B complex compound may be applied for clinical usage and therapeutic regimen.
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Affiliation(s)
- Chia-Chih Lin
- Department of Physical Education and Kinesiology, National Dong Hwa University, Hualien, Taiwan
| | - Nan-Kuang Hsieh
- Department of Family Medicine, Tao-Yuan General Hospital, Department of Health, Executive Yuan, Taoyuan, Taiwan
- Department of Pathology, China Medical University, Taichung, Taiwan
| | - Huey Ling Liou
- Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsing I Chen
- Institute of Physiological and Anatomical Medicine, Tzu Chi University, Hualien, Taiwan
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Zhu J, Piao RL, Gao RP. Toll-like receptor 4 signaling pathway and pancreatitis. Shijie Huaren Xiaohua Zazhi 2012; 20:271-275. [DOI: 10.11569/wcjd.v20.i4.271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The pathogenesis of pancreatitis has long been a hot topic in basic and clinical research but is still not fully clarified. Toll-like receptor 4 (TLR4) recognizes the lipopolysaccharide (LPS) of Gram-negative bacteria and stimulates the synthesis and release of inflammatory cytokines through activation of the NF-κB signaling pathway, which ultimately results in inflammatory responses that involve multiple organs. Animal and clinical studies have shown that the TLR4 signal pathway plays an important role in the development of tissue injury during acute pancreatitis (AP) and up-regulation of TLR4 and the TLR4 signaling pathway contributes to the development of multiple organ dysfunction syndrome (MODS) associated with severe acute pancreatitis (SAP) by increasing proinflammatory cytokines. Therefore, further studies are required to clarify the role of the TLR 4 signaling pathway in the pathogenesis of pancreatitis to explore novel methods for treating this disease.
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Hegyi P, Rakonczay Z. The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas. Antioxid Redox Signal 2011; 15:2723-2741. [PMID: 21777142 DOI: 10.1089/ars.2011.4063] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
SIGNIFICANCE Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. RECENT ADVANCES The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. CRITICAL ISSUES Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. FUTURE DIRECTIONS Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.
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Affiliation(s)
- Péter Hegyi
- First Department of Medicine, University of Szeged, Szeged, Hungary
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Wang M, Liu T, Wang D, Zheng Y, Wang X, He J. Therapeutic effects of pyrrolidine dithiocarbamate on acute lung injury in rabbits. J Transl Med 2011; 9:61. [PMID: 21569464 PMCID: PMC3112441 DOI: 10.1186/1479-5876-9-61] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2011] [Accepted: 05/13/2011] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is an early characteristic of multiple organ dysfunction, responsible for high mortality and poor prognosis in patients. The present study aims to evaluate therapeutic effects and mechanisms of pyrrolidine dithiocarbamate (PDTC) on ALI. METHODS Alveolar-arterial oxygen difference, lung tissue edema and compromise, NF-κB activation in polymorphonuclear neutrophil (PMN), and systemic levels of tumor necrosis factor-alpha (TNFa) and intercellular adhesion molecule-1 (ICAM-1) in rabbits induced by the intravenous administration of lipopolysaccharide (LPS) and treated with PDTC. Production of TNFa and IL-8, activation of Cathepsin G, and PMNs adhesion were also measured. RESULTS The intravenous administration of PDTC had partial therapeutic effects on endotoxemia-induced lung tissue edema and damage, neutrophil influx to the lung, alveolar-capillary barrier dysfunction, and high systemic levels of TNFa and ICAM-1 as well as over-activation of NF-κB. PDTC could directly and partially inhibit LPS-induced TNFa hyper-production and over-activities of Cathepsin G. Such inhibitory effects of PDTC were related to the various stimuli and enhanced through combination with PI3K inhibitor. CONCLUSION NF-κB signal pathway could be one of targeting molecules and the combination with other signal pathway inhibitors may be an alternative of therapeutic strategies for ALI/ARDS.
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Affiliation(s)
- Meitang Wang
- Department of Emergency Medicine, The Second Military University Changhai Hospital, China
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