1.The correlation between expression of DLC-1 and colon cancer staging
Jian'gang WANG ; Quan SHAO ; Yingbin WANG ; Yuanlian WAN ;
Cancer Research and Clinic 2014;26(4):246-249
Objective To investigate the relationship between the expression level of deleted in liver cancer-1 (DLC-1) gene and colon cancer staging or lymph nodes metastatic ratio.Methods Total 60 resection specimens were collected from colon cancer patients between September 2009 and September 2011,and 10 resection specimens from patients with trauma,colonic diverticulitis and colitis were used as the control.The DLC-1 mRNA level was measured with real time quantitative RT-PCR in colon cancer patients and the control group.TNM system was used for colon cancer staging.The linear correlation analysis was performed to determine the relationship between DLC-1 expression level and colon cancer staging or lymph nodes metastatic ratio.Results The mRNA level of DLC-1 was significantly reduced in colon cancer tissues in comparison to that in adjacent normal tissues,while adjacent tissues showed significantly lower DLC-1 level than normal clone tissues.The expression of DLC-1 was negatively correlated with both colon cancer stage and the lymph nodes metastatic ratio (r =0.46,P < 0.05).Conclusions DLC-1 expression was negatively correlated with pathological stage and lymph node metastasis ratio,indicating a critical role of DLC-1 gene in colon cancer genesis,which provide a possible new direction for colon cancer research.
2.Effect of sufentanil postconditioning on level of cathepsin B in myocardium during ischemia-reperfusion in rats
Shouyuan TIAN ; Wenjie ZHANG ; Lixia NIE ; Jian'gang WANG ; Jian ZHU ; Xin WANG ;
Chinese Journal of Anesthesiology 2017;37(4):435-438
Objective To evaluate the effect of sufentanil postconditioning on the level of cathepsin B in the myocardium during ischemia-reperfusion (I/R) in the rats.Methods Eighteen healthy adult male Sprague-Dawley rats,weighing 250-300 g,were divided into 3 groups (n=6 each) using a random nunber table:shamn operation group (group S),group I/R and sufentanil postconditioning group (group SP).The rats were anesthetized with intraperitoneal 20% urethane 5 ml/kg.Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.At 5 min before reperfusion,sufentanil 1.0 μg/kg was intravenously injected in group SP,and the equal volume of normal saline was given instead in S and I/R groups.At the end of reperfusion,blood samples from the abdominal aorta were collected for determination of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) concentrations,and myocardial specimnens were obtained for examination of the ultrastructure of cardiomyocytes (using transmission electron microscopy) and for determination of Beclin1,microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) and cathepsin B expression (by Western blot) and cathepsin B activity (by fluorometric assay).Results Compared with group S,the serum cTnI and CK-MB concentrations were significantly increased,the expression of Beclin-1,LC3 Ⅱ and cathepsin B was up-regulated,and the activity of cathepsin B was enhanced in I/R and SP groups (P<0.05).Compared with group I/R,the serum cTnI and CK-MB concentrations were significantly decreased,the expression of Beclin-1 and LC3 Ⅱ was down-regulated,the expression of cathepsin B was up-regulated,and the activity of cathepsin B was enhanced (P<0.05),the pathological changes of myocardial tissues were signifieantly attenuated,and autophagosomes were reduced in group SP.Conclusion The mechanism by which sufentanil postconditioning inhibits cardiomyocyte autophagy during myocardial I/R is probably related to increased expression and activity of cathepsin B in rats.
3.Correlation analysis of clinical indicators and liver failure-related prognostic score associated with prognosis in patients with amanita phalloides poisoning
Xiaoli LIANG ; Shanshou LIU ; Bingyue WANG ; Xiaojun ZHAO ; Chujun DUAN ; Xiaomin HU ; Jian'gang XIE
Chinese Critical Care Medicine 2022;34(11):1178-1182
Objective:To analyze and compare the clinical indicators and the liver failure-related prognostic score of patients with amanita phalloides poisoning with different prognoses, and to explore potential prognostic indicators.Methods:A retrospective case-control study was conducted. The clinical data of 52 patients with amanita phalloides poisoning admitted to the department of emergency of Xijing Hospital Affiliated to Air Force Medical University from September 2016 to September 2021 were collected, including general information (gender, age), clinical indicators at admission [mean arterial pressure (MAP), total bilirubin (TBil), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK), D-dimer, fibrinogen degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), white blood cell count (WBC), platelet count (PLT)], liver failure-related prognostic score [sequential organ failure assessment (SOFA), chronic liver failure (CLIF)-SOFA score, European Foundation for the Study of Chronic Liver Failure-organ failure (CLIF-C OF)], and 28-day outcome. The clinical indicators and liver failure-related prognostic scores of the patients with different prognoses were compared. Receiver operator characteristic curve (ROC curve) was used to determine the prognostic value of statistically significant indicators between different prognosis of patients with amanita poisoning.Results:A total of 45 patients were enrolled, of which 38 survived and 7 died within 28 days. The coagulation indicators including PT, APTT, INR, and liver failure-related prognostic scores including SOFA score, CLIF-SOFA score, and CLIF-C OF score in the patients of death group were significantly higher than those in the survival group [PT (s): 69.59±15.94 vs. 25.99±4.64, APTT (s): 83.44±17.82 vs. 42.64±3.79, INR: 6.13±1.47 vs. 2.07±0.33, SOFA score: 11.57±1.38 vs. 6.03±0.77, CLIF-SOFA score: 9.86±2.17 vs. 5.55±0.67, CLIF-C OF score: 11.71±0.97 vs. 8.37±0.35], and PLT was significantly lowered (×10 9/L: 80.57±29.65 vs. 169.60±11.80, all P < 0.05). ROC curves showed that coagulation indicators including PT, APTT, INR, PLT, and liver failure-related prognostic scores including SOFA score and CLIF-C OF score were associated with the prognosis of patients with amanita phalloides poisoning, with the area under the ROC curve (AUC) of > 0.75. The sensitivity of the clinical indicators was above 85%, and the AUC and specificity of INR were the highest, which were 0.88 [95% confidence interval (95% CI) was 0.74-1.00] and 83.0%, respectively; meanwhile, the sensitivity of the liver failure-related prognostic scores was 100%, and the AUC and specificity of the CLIF-C OF score were the highest, which were 0.86 (95% CI was 0.74-0.99) and 66.0%, respectively. Conclusion:INR and CLIF-C OF score can be used to evaluate the poor prognosis of patients with amanita phalloides poisoning.
4.Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress.
Maoxian YANG ; Haitao TIAN ; Peng SHEN ; Longsheng XU ; He LIU ; Jian'gang ZHU ; Qianqian WANG ; Yunchao SHI
Chinese Critical Care Medicine 2023;35(4):393-397
OBJECTIVE:
To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS).
METHODS:
A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope.
RESULTS:
Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05).
CONCLUSIONS
Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.
Male
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Rats
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Animals
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Rats, Sprague-Dawley
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NF-kappa B
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Actins
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Caspase 3
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Curcumin
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Lipocalin-2
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Toll-Like Receptor 4
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Inflammasomes
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NLR Family, Pyrin Domain-Containing 3 Protein
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Reactive Oxygen Species
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Saline Solution
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Kidney
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Superoxide Dismutase