scholarly journals Acanthopanaxversus3-Methyladenine Ameliorates Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting the Autophagic Pathway in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaohong Wang ◽  
Guoxiong Zhou ◽  
Chun Liu ◽  
Ronglong Wei ◽  
Shunxing Zhu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Mrna Expression ◽  
Serum Amylase ◽  
Sodium Taurocholate ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Therapeutic Effects ◽  
Expression Levels ◽  
Treatment Groups ◽  
Mrna Expression Levels

Objectives. To observe the therapeutic effects of Acanthopanax and 3-methyladenine against severe acute pancreatitis (SAP).Methods. Sodium taurocholate-induced SAP rats were equally randomized into a SAP group, an Acanthopanax group, and a 3-methyladenine group. Serum amylase levels were determined by ELISA; protein and mRNA expression levels of nucleus nuclear factor kappa B (NF-κB) p65, light chain 3II (LC3-II), and Beclin-1 and mRNA expression levels of Class III phosphatidylinositol 3-kinase (PI3K-III) in pancreas tissue were detected by Western blot and quantitative real-time PCR, respectively; mortality and pathological change of the pancreas were observed at 3, 12, and 24 h after operation.Results. There was no significant difference in mortality between SAP group and both treatment groups (P>0.05). Serum amylase levels, protein, and mRNA expression levels of nucleus NF-κB p65, LC3-II, and Beclin-1 protein, mRNA expression levels of PI3K-III, and pathological score of the pancreas in both treatment groups were significantly lower than those in SAP group at 12 and 24 h after operation (P<0.05or 0.01). The number of autophagosomes and autophagolysosomes of pancreatic acinar cells in both treatment groups was smaller than that in SAP group at 12 and 24 h.Conclusions. Acanthopanax and 3-methyladenine had similar therapeutic effects against SAP in rats. The mechanism may be through inhibiting abnormal autophagy activation of pancreatic acinar cells.

scholarly journals α-Lipoic Acid Inhibits IL-6 Expression by Upregulating PPAR-γ-Mediated Expression of Antioxidants in Cerulein/Resistin-Stimulated Pancreatic Acinar Cells

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1133-1133
Author(s):  
Yujin Lee ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Acute Pancreatitis ◽  
Mrna Expression ◽  
Lipoic Acid ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Pcr Analysis ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Ar42j Cells ◽  
Ppar Γ

Abstract Objectives Oxidative stress is regarded as a major pathogenic factor in acute pancreatitis. Obesity is thought to be a negative prognostic factor in acute pancreatitis. Levels of serum resistin, an adipocytokine secreted by fat tissues, increase with obesity. Recent study showed that resistin aggravates the expression of inflammatory cytokines such as interleukine-6 (IL-6) and production of reactive oxygen species (ROS) in pancreatic acinar cells stimulated with cerulein, a cholecystokinin analogue, as an in vitro acute pancreatitis model. Peroxisome proliferator-activated receptor (PPAR)-γ increases expression of antioxidant enzymes such as catalase and heme oxygenase-1 (HO-1). α-Lipoic acid is a powerful antioxidant and anti-inflammatory nutrient. The present study was purposed to investigate whether α-lipoic acid inhibits IL-6 expression in resistin/cerulein-stimulated pancreatic acinar cells and to determine whether it reduces ROS in AR42J cells by upregulating PPAR-γ-mediated expression of HO-1 and catalase in pancreatic acinar cells. Methods Rat pancreatic acinar cell line, AR42J cells, were stimulated with resistin (2 ng/ml) and cerulean (10−8 M), in the presence or absence of α-lipoic acid. mRNA expression of IL-6 was determined by real-time PCR analysis. ROS levels were measured using DCF-DA fluorescence. Expression of PPAR-γ, HO-1, and catalase were determined by Western blotting. Results α-Lipoic acid significantly decreased IL-6 mRNA expression and ROS production in resistin/cerulein-stimulated AR42J cells. α-Lipoic acid also increased expression of PPAR-γ, HO-1 and catalase. Inhibitory effect of α-lipoic acid on resistin/cerulein–induced IL-6 expression was suppressed by addition of a specific PPAR-γ inhibitor GW9662. GW9662 reversed the effect of α-lipoic acid on expression of HO-1 and catalase in AR42J cells. Conclusions α-Lipoic acid suppresses cerulein/resistin-induced IL-6 expression and ROS production through PPAR-γ-mediated expression of HO-1 and catalase in pancreatic acinar cells. Funding Sources This study was supported by a Brain Korea 21 FOUR Project, Yonsei University, Seoul, Republic of Korea.

scholarly journals Effect of dietary pyrroloquinoline quinone disodium in sows on intestinal health of the offspring

2020 ◽  
Author(s):  
Chenxi Wang ◽  
Boru Zhang ◽  
Hongyun Zhang ◽  
Wei Yang ◽  
Qingwei Meng ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Pyrroloquinoline Quinone ◽  
Intestinal Health ◽  
Weaned Piglets ◽  
Expression Levels ◽  
Treatment Groups ◽  
Positive Effects ◽  
Newborn Piglets ◽  
Essential Nutrient ◽  
Mrna Expression Levels

Abstract Background: Pyrroloquinoline quinone (PQQ) is a putative essential nutrient and redox modulator in microorganisms, cell and animal models. The objective of this study was to investigate the effects of pyrroloquinoline quinone disodium (PQQ·Na2) in sows during gestation and lactation on intestinal health in the offspring.Results: The activities of SOD and GSH-Px were significantly (P<0.05) increased by PQQ·Na2 supplementation, and MDA activity was decreased (P<0.05) in the plasma of piglets. CAT, SOD and GSH-Px activities were significantly (P<0.05) increased, and MDA activity was decreased (P<0.05) in the small intestine of piglets. The mRNA expression levels of SOD1, CAT and MGST1 in the jejunum were increased in newborn piglets (P<0.05), and the mRNA expression levels of HO1, SOD1, CAT, SOD2, GPX4, GPX1 and GCLC in the jejunum were increased in weaned piglets (P<0.05). The mRNA expression of ZO-1 was increased (P<0.05) in the jejunum of newborn piglets, and the mRNA expression of Occludin and ZO-1 was increased (P<0.05) in the jejunum of weaned piglets. The villous height of the duodenum and jejunum of weaned piglets was increased (P<0.05) by dietary PQQ·Na2. In weaned piglets, Bacteroidetes and Firmicutes were the most prevalent phyla in both the Con and PQQ·Na2 treatment groups, and the most prevalent genera were Alloprevotella and Bacteroides. At the phylum level, the abundance of Firmicutes was significantly increased (P<0.05), and the abundance of Proteobacteria was significantly decreased (P<0.05). At the genus level, the abundance of Alloprevotella was significantly increased (P<0.05), and the abundance of Actinobacillus and Escherichia was decreased (P<0.05).Conclusions: In conclusion, dietary supplementation with PQQ·Na2 in sows during gestation and lactation had positive effects on intestinal health in offspring.

scholarly journals Sinisan Protects Primary Hippocampal Neurons Against Corticosterone by Inhibiting Autophagy via the PI3K/Akt/mTOR Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingjia Zhang ◽  
Yi Zhang ◽  
Haitao Sun ◽  
Hui Ni ◽  
Jialing Sun ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Mtor Pathway ◽  
Therapeutic Effects ◽  
Protein Ratio ◽  
Expression Levels ◽  
Primary Hippocampal Neurons ◽  
Mrna Expression Levels

Objective: Corticosterone causes significant neurotoxicity in primary hippocampal neurons which is associated with depression. Dysfunctional autophagy is implicated in cognitive impairment and depressive-like behavior. The traditional Chinese medicine Sinisan (SNS) is highly effective in clinical treatment of depression. However, the molecular mechanisms underlying therapeutic effects of SNS are unknown.Purpose: The aim of this study was to elucidate the protective effect of SNS and the underlying mechanisms against corticosterone-induced neuronal damage.Study Design: The effects of serum derived from rats containing SNS (or untreated controls) on the expression of autophagy-related molecules in primary rat hippocampal neurons exposed to different concentrations of corticosterone for different intervals were explored.Methods: CCK-8 assay, LDH assay were used to analyze cell viability and LDH activity. Western blot, qRT-PCR, and immunofluorescence assays were used to determine protein and mRNA expression levels of molecules such as LC3, p62, Beclin1, ULK1, PI3K, p-PI3K, Akt p-Akt, mTOR, p-mTOR, p70S6, p-p70S6, 4ebp1 and p-4ebp1.Results: Corticosterone induced a dose- and time-dependent reduction in cellular viability. Moreover, corticosterone (100–400 μM) treatment for 24 h increased LC3-II/LC3-I protein ratio, increased Beclin1 and ULK1 protein expression levels, and decreased p62, PI3K, p-PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein expression levels. Notably, SNS-containing serum reversed corticosterone-induced reduction of neuronal viability, and increased p62, PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein and mRNA expression levels. In addition, SNS-containing serum decreased LC3-II/LC3-I protein ratio, and downregulated Beclin1, and ULK1 protein and mRNA expression in primary hippocampal neurons.Conclusion: SNS protects primary hippocampal neurons against corticosterone-induced neurotoxicity by preventing excessive autophagy through activation of PI3K/AKT/mTOR pathway.

scholarly journals In vivo Therapeutic Effects and Mechanisms of Hydroxyasiaticoside Combined With Praziquantel in the Treatment of Schistosomiasis Induced Hepatic Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Huilong Fang ◽  
Ling Yu ◽  
Da You ◽  
Nan Peng ◽  
Wanbei Guo ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mrna Expression ◽  
Hepatic Fibrosis ◽  
Inflammatory Factors ◽  
Control Group ◽  
Therapeutic Effects ◽  
Type I ◽  
Expression Levels ◽  
Tnf Α ◽  
Mrna Expression Levels

Schistosomiasis has been a fatal obstinate disease that threatens global human health, resulting in the granulomatous inflammation and liver fibrosis.Objective:The aim of this study was to evaluate the therapeutic effects and mechanisms of hydroxyasiaticoside combined with praziquantel in the treatment of schistosomiasis-induced liver fibrosis.Methods:Mice were randomly distributed into four experimental groups: normal control group, model group, praziquantel group, praziquantel + hydroxyasiaticoside group. Except for the normal control group, they were infected with Schistosomia cercariae through the abdominal skin to induce liver fibrosis. In the intervention group, mice were administered with the respective drugs by gavage after 8 weeks of infection. At the end of the treatment, mice were sacrificed to collect blood for the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Moreover, the liver was excised, weighed, and liver indices were calculated. Histopathological examination was performed to assess liver morphology. Besides, the expression of collagen type I and III in liver was determined; the mRNA expression levels of IL-6 and TNF-α in liver tissues were measured using Real-time PCR while ELISA and western blotting were performed on liver tissue homogenate to determine the protein expression of IL-6 and TNF-α.Results:The combination of praziquantel and hydroxyasiaticoside lowered the pathological scores of schistosomiasis-induced hepatic fibrosis, the liver indice, serum AST and ALT levels, improved liver morphology, downregulated the expression levels of hepatic type I and III collagen, inhibited the mRNA expression levels of pro-inflammatory factors (IL-6 and TNF-α) in the liver of mice relative to the praziquantel alone.Conclusion:The combination of hydroxyasiaticoside and praziquantel is a potential therapeutic option for schistosomiasis-induced hepatic fibrosis. Notably, this combination noticeably suppresses the protein and mRNA expression levels of pro-inflammatory factors (TNF-α and IL-6) in the liver.

scholarly journals Efficacy of 5-Aminolevulinic Acid in Photodynamic Detection and Photodynamic Therapy in Veterinary Medicine

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 495 ◽  
Author(s):  
Tomohiro Osaki ◽  
Inoru Yokoe ◽  
Yuji Sunden ◽  
Urara Ota ◽  
Tomoki Ichikawa ◽  
...  
Keyword(s):  
Veterinary Medicine ◽  
Mrna Expression ◽  
Tumor Cells ◽  
Aminolevulinic Acid ◽  
Metabolic Enzyme ◽  
Tumor Control ◽  
Therapeutic Effects ◽  
Expression Levels ◽  
Mrna Expression Levels

5-Aminolevulinic acid (5-ALA), a commonly used photosensitizer in photodynamic detection (PDD) and therapy (PDT), is converted in situ to the established photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. To extend 5-ALA-PDT application, we evaluated the PpIX fluorescence induced by exogenous 5-ALA in various veterinary tumors and treated canine and feline tumors. 5-ALA-PDD sensitivity and specificity in the whole sample group for dogs and cats combined were 89.5 and 50%, respectively. Notably, some small tumors disappeared upon 5-ALA-PDT. Although single PDT application was not curative, repeated PDT+/−chemotherapy achieved long-term tumor control. We analyzed the relationship between intracellular PpIX concentration and 5-ALA-PDT in vitro cytotoxicity using various primary tumor cells and determined the correlation between intracellular PpIX concentration and 5-ALA transporter and metabolic enzyme mRNA expression levels. 5-ALA-PDT cytotoxicity in vitro correlated with intracellular PpIX concentration in carcinomas. Ferrochelatase mRNA expression levels strongly negatively correlated with PpIX accumulation, representing the first report of a correlation between mRNA expression related to PpIX accumulation and PpIX concentration in canine tumor cells. Our findings suggested that the results of 5-ALA-PDD might be predictive for 5-ALA-PDT therapeutic effects for carcinomas, with 5-ALA-PDT plus chemotherapy potentially increasing the probability of tumor control in veterinary medicine.

scholarly journals Protective effects of baicalin on caerulein-induced AR42J pancreatic acinar cells by attenuating oxidative stress through miR-136-5p downregulation

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110261
Author(s):  
Zhu-fen Zhao ◽  
Ye Zhang ◽  
Yang Sun ◽  
Chun-hai Zhang ◽  
Ming-wei Liu
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Relative Survival ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Amylase Level ◽  
Sod1 Gene ◽  
Expression Levels ◽  
Thiazolyl Blue Tetrazolium Bromide ◽  
Gene And Protein Expression

Baicalin, the main active component of Scutellaria baicalensis, has antioxidant and anti-apoptotic effects and is used to treat acute pancreatitis; however, its specific mechanism is unclear. This study aims to determine the protective effect and underlying mechanism of baicalin on AR42J pancreatic acinar cell injury. AR42J acinar cells (caerulein, 10 nmol/L) were induced in vitro to establish a cell model for acute pancreatitis. Cell relative survival was measured by thiazolyl blue tetrazolium bromide, and cell apoptosis and death were examined by flow cytometry. The expression levels of superoxide dismutase1 (SOD1), Bax, survivin, Bcl-2, caspase-3, and caspase-7 proteins were analyzed by Western blot, and those of SOD1 mRNA and miR-136-5p were determined by RT-PCR. The activities of GSH, SOD1, ROS, and MDA were also investigated. Compared with those of the caerulein group, the relative survival rate and activity of AR42J pancreatic acinar cells with different baicalin concentrations were significantly increased ( p < 0.05), and the supernatant amylase level was markedly decreased ( p < 0.05). In addition, the ROS and MDA activities and mir-136-5p expression were significantly decreased, and the GSH activities and SOD1 gene and protein expression levels were markedly increased ( p < 0.05). These results suggest that baicalin reduced the caerulein-induced death of AR42J acinar cells and alleviated the caerulein-induced injury in pancreatic acinar cells by inhibiting oxidative stress. The mechanism may be related to the decreased expression of Mir-136-5p and the increased expression of SOD1 gene and protein.

scholarly journals Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ali A. Aghdassi ◽  
Daniel S. John ◽  
Matthias Sendler ◽  
Christian Storck ◽  
Cindy van den Brandt ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Serine Protease ◽  
Acinar Cells ◽  
Neutrophil Infiltration ◽  
Cathepsin G ◽  
Pancreatic Acinar Cells ◽  
Neutrophil Granulocyte ◽  
Zymogen Activation ◽  
Trypsinogen Activation ◽  
Extracellular Matrix Components

AbstractAcute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG−/− mice and corresponding controls acute experimental pancreatitis was induced by serial caerulein injections. Severity was assessed by histology, serum enzyme levels and zymogen activation. Neutrophil infiltration was quantified by chloro-acetate ersterase staining and myeloperoxidase measurement. CTSG was expessed in inflammatory cells but not in pancreatic acinar cells. CTSG had no effect on intra-acinar-cell trypsinogen activation. In CTSG−/− mice a transient decrease of neutrophil infiltration into the pancreas and lungs was found during acute pancreatitis while the disease severity remained largely unchanged. CTSG is involved in pancreatic neutrophil infiltration during pancreatitis, albeit to a lesser degree than the related neutrophil (PMN) elastase. Its absence therefore leaves pancreatitis severity essentially unaffected.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Inflammatory Infiltration ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Inflammatory Damage ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

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