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  • Hindawi Limited  (13)
  • 1
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2020 ( 2020-04-08), p. 1-12
    Abstract: Background . Danshen ( Salvia miltiorrhiza Bunge) and its main active component Tanshinone IIA (TSA) are clinically used in China. However, the effects of TSA on acute pancreatitis (AP) and its potential mechanism have not been investigated. In this study, our objective was to investigate the protective effects of TSA against AP via three classic mouse models. Methods . Mouse models of AP were established by caerulein, sodium taurocholate, and L-arginine, separately. Pancreatic and pulmonary histopathological characteristics and serum amylase and lipase levels were evaluated, and changes in oxidative stress injury and the ultrastructure of acinar cells were observed. The reactive oxygen species (ROS) inhibitor N-Acetylcysteine (NAC) and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice were applied to clarify the protective mechanism of the drug. Results . In the caerulein-induced AP model, TSA administration reduced serum amylase and lipase levels and ameliorated the histopathological manifestations of AP in pancreatic tissue. Additionally, TSA appreciably decreased ROS release, protected the structures of mitochondria and the endoplasmic reticulum, and increased the protein expression of Nrf2 and heme oxygenase 1 of pancreatic tissue. In addition, the protective effects of TSA against AP were counteracted by blocking the oxidative stress (NAC administration and Nrf2 knockout in mice). Furthermore, we found that TSA protects pancreatic tissue from damage and pancreatitis-associated lung injury in two additional mouse models induced by sodium taurocholate and by L-arginine. Conclusion . Our data confirmed the protective effects of TSA against AP in mice by inhibiting oxidative stress via the Nrf2/ROS pathway.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2455981-7
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  • 2
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2021 ( 2021-11-17), p. 1-17
    Abstract: As a calcium-regulated protein, CaMK II is closely related to cell death, and it participates in the development of pathological processes such as reperfusion injury, myocardial infarction, and oligodendrocyte death. The function of CaMK II activation in acute pancreatitis (AP) remains unclear. In our study, we confirmed that the expression of p-CaMK II was increased significantly and consistently in injured pancreatic tissues after caerulein-induced AP. Then, we found that KN93, an inhibitor of CaMK II, could mitigate the histopathological manifestations in pancreatic tissues, reduce serum levels of enzymology, and decrease oxidative stress products. Accordingly, we elucidated the effect of KN93 in vitro and found that KN93 had a protective effect on the pancreatic acinar cell necroptosis pathway by inhibiting the production of ROS and decreasing the expression of RIP3 and p-MLKL. In addition, we identified the protective effect of KN93 on AP through another mouse model induced by pancreatic duct ligation (PDL). Together, these data demonstrated that CaMK II participates in the development of AP and that inhibiting CaMK II activation could protect against AP by reducing acinar cell necroptosis, which may provide a new idea target for the prevention and treatment of AP in the clinic.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2455981-7
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  • 3
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2021 ( 2021-3-9), p. 1-13
    Abstract: Background and Purpose. Previous studies showed that Maresin1 (MaR1), one of the metabolites from docosahexaenoic acid (DHA), could alleviate acute inflammation and prompt inflammation resolution. Also, it attenuated pancreatic injury in caerulein-induced acute pancreatitis (AP) in mice. However, the mechanisms underlying this suppression of inflammation and AP remain unknown. Method. Repeated caerulein injection was used to induce AP and chronic pancreatitis (CP) models in mice. The histopathological and serological changes were examined for evaluating the severity of the AP model, and flow cytometry was used for detecting macrophage phagocytosis and phenotype. Meanwhile, clodronate liposomes were used for macrophage depletion in mice. Finally, the CP model was adopted to further observe the protective effect of MaR1. Result. MaR1 administration manifested the improved histopathological changes and the lower serum levels of amylase and lipase. However, MaR1 played no protective role in the pancreatic acinar cell line in vitro. It obviously reduced the macrophage infiltration in the injured pancreas, especially M1-type macrophages. After macrophage clearance, MaR1 showed no further protection in vivo. This study also demonstrated that MaR1 could alleviate fibrosis to limit AP progression in the CP model. Conclusion. Our data suggests that MaR1 was a therapeutic and preventive target for AP in mice, likely operating through its effects on decreased macrophage infiltration and phenotype switch.
    Type of Medium: Online Resource
    ISSN: 1466-1861 , 0962-9351
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2008065-7
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  • 4
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2018 ( 2018-09-06), p. 1-3
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2008065-7
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  • 5
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2018 ( 2018-07-29), p. 1-1
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2008065-7
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  • 6
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2018 ( 2018), p. 1-12
    Abstract: Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.
    Type of Medium: Online Resource
    ISSN: 1942-0900 , 1942-0994
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
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  • 7
    Online Resource
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    Hindawi Limited ; 2021
    In:  BioMed Research International Vol. 2021 ( 2021-1-6), p. 1-9
    In: BioMed Research International, Hindawi Limited, Vol. 2021 ( 2021-1-6), p. 1-9
    Abstract: Natural killer T (NKT) cells are a key component of innate immunity. Importantly, a growing body of evidence indicates that NKT cells play an integral role in various acute and chronic liver injuries. NKT cells participate in the progression of an injury through the secretion of cytokines, which promote neutrophil infiltration and enhance Fas ligand (FasL) and granzyme-mediated NKT cytotoxic activity. Therefore, examining the role of NKT cells in hepatic disease is critical for a comprehensive understanding of disease pathogenesis and may provide insight into novel approaches for treatment. For more than a century, mouse models that imitate the physiopathological conditions of human disease have served as a critical tool in biological and medical basic research, including studies of liver disease. Here, we review the role of NKT cells in various mouse models of hepatitis.
    Type of Medium: Online Resource
    ISSN: 2314-6141 , 2314-6133
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2698540-8
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  • 8
    In: BioMed Research International, Hindawi Limited, Vol. 2021 ( 2021-6-11), p. 1-8
    Abstract: Objective. According to reports, liver enzymes might play a role in the incidence and development of cardiometabolic diseases such as metabolic syndrome (MetS), hypertension (HTN), and cardiovascular diseases (CVD). We conducted a study to investigate this hypothesis among the Iranian Kurdish population. Methods. We analyzed data from the baseline phase of the Ravansar noncommunicable disease (RaNCD) cohort. The association between liver enzymes (ALT, AST, ALT/AST ratio, GGT, and ALP) with cardiometabolic disease risk factors was investigated by multiple linear regression. The odds ratio of cardiometabolic diseases in each quartile category of liver enzyme concentration was estimated using multivariable logistic regression. Results. The mean age of participants was 47.3 ± 4.1 years (48.1 years in males and 51.8 years in females). In the adjusted model, all enzymes were positively associated with MetS, HTN, and CVD risk factors except for the ALT/AST ratio with SBP and DBP. In the adjusted model, subjects in the fourth quartile for GGT, ALT/AST ratio, ALT, ALP, and AST had 3.29-, 2.94-, 2.45-, 2.00-, and 1.19-fold increased risk for MetS compared with subjects in the first quartile. Increased levels of GGT and ALP were positively associated with the risk of HTN ( ORs = 1.33 , 95 % CI = 1.03 – 1.71 for GGT; ORs = 1.32 , 95 % CI = – 1.68 for ALP). An increased GGT level was significantly associated with CVD ( ORs = 1.54 , 95 % CI = 1.03 – 1.68 ). Within the normal range quartile, ALT had a significant correlation with the incidence of MetS. Conclusion. According to the present study, the levels of liver enzymes could be considered for early diagnosis of MetS, HTN, and CVD.
    Type of Medium: Online Resource
    ISSN: 2314-6141 , 2314-6133
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
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  • 9
    In: BioMed Research International, Hindawi Limited, Vol. 2019 ( 2019-01-22), p. 1-7
    Abstract: Background and Aim . The incidence of nonalcoholic fatty liver disease (NAFLD) as a metabolic disease is increasing annually. In the present study, we aimed to explore the influence of NAFLD on the severity of acute pancreatitis (AP). Methods . The severity of AP was diagnosed and analyzed according to the 2012 revised Atlanta Classification. Outcome variables, including the severity of AP, organ failure (all types of organ failure), and systemic inflammatory response syndrome (SIRS), were compared for patients with and without NAFLD. Results . Six hundred and fifty-six patients were enrolled in the study and were divided into two groups according to the presence or absence of NAFLD. The non-NAFLD group contained 278 patients and the main etiology in this group was gallstone. The NAFLD group consisted of 378 patients and the main etiology was hyperlipidemia. The incidence of mild AP, moderately severe AP, and severe AP was 77.30%, 18.3%, and 4.3% in the non-NAFLD group and 58.2%, 33.9%, and 7.9% in the NAFLD group, respectively. There were significant differences between the two groups according to the severity of AP (P ≤ 0.001). In addition, the Ranson and BISAP scores as well as the incidence of SIRS and organ failure in the NAFLD group were higher than those in the non-NAFLD group (all P 〈 0.05). The patients were further divided into non-NAFLD, mild-NAFLD, and moderate-severe NAFLD (M+S-NAFLD) groups. The results showed that the severity of AP increased gradually from the non-NAFLD group to the M+S-NAFLD group. In addition, the incidence rates of SIRS and organ failure showed an upward trend with the aggravation of fatty liver severity. Multivariate logistic analysis showed that patients with NAFLD, especially those with M+S-NAFLD, had higher risks of SIRS and organ failure. Conclusions . Compared with non-NAFLD, NAFLD has a clinically relevant impact on the severity of AP and may be an early prognostic parameter for patients with AP.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2019
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  • 10
    In: BioMed Research International, Hindawi Limited, Vol. 2016 ( 2016), p. 1-10
    Abstract: Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF- κ B p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2016
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