1.Association of serum inflammatory cytokines and Resolvin D1 concentration with pathological stage of colon cancer.
Qiulin ZHUANG ; Qingyang MENG ; Qiulei XI ; Guohao WU
Chinese Journal of Gastrointestinal Surgery 2018;21(11):1285-1290
OBJECTIVE:
To investigate the levels of serum inflammatory cytokines and Resolvin D1 (RvD1) and their association with pathological staging of colon cancer.
METHODS:
Clinical data of 50 colon cancer patients (colon cancer group) admitted to the General Surgery Department of Zhongshan Hospital of Fudan University from January to December 2016 and 5 ml of whole blood specimen were collected at admission. During the same period, 50 healthy volunteers were enrolled (healthy volunteer group). Inclusion criteria for the colon cancer group: colon cancer diagnosed by preoperative colonoscopy and pathology; no recent enteral or parenteral nutrition support treatment or use of oral nutrition preparation; age ≤85 years; no surgical contraindications by preoperative evaluation; no history of taking fish oil-related preparations; no radiotherapy or chemotherapy before surgery. Healthy volunteer group enrollment criteria: no history of malignant tumors; no organ with organic lesions detected by the healthy examination center of our hospital; detection indicators in normal reference range; no administration of fish oil-related preparations; age ≤ 85 years. Serum inflammatory factors(IL-1β, IL-6, IL-10 and TNF-α) concentrations were detected by chemiluminescence immunoassay; serum RvD1 concentration was measured by enzyme-linked immunosorbent assay. The levels of inflammatory factors and RvD1 were compared between the two groups, and their associations with TNM staging of colon cancer patients were analyzed.
RESULTS:
There were no significant differences in age, gender and nutrition-related indicators between the two groups (all P>0.05). There were 31 males and 19 females in the healthy volunteer group with age of (61.8±11.6) years. There were 23 males and 27 females in the colon cancer group with age of (65.4±12.4) years. According to the 7th edition of the American Cancer Society TNM staging criteria, 10 cases were stage I, 13 cases stage II, 17 cases stage III, and 10 cases stage IV. Compared with healthy volunteer group, colon cancer group had higher serum IL-1β [(3.89±0.24)×10 μg/L vs.(1.55±0.37)×10 μg/L, t=37.52, P<0.01], higher IL-6 [(129.14±3.07)×10 μg/L vs.(51.46±3.14)×10 μg/L, t=125.08, P<0.01], higher IL-10 [(100.59±8.69)×103 μg/L vs.(27.57±4.77)×10 μg/L, t=52.09, P<0.01] and higher TNF-α [(114.31±4.43)×10 μg/L vs.(41.04±5.27)×10 μg/L, t=75.25, P<0.01], while lower RvD1 [(34.19±1.93)×10 μg/L vs.(77.76±1.02)×10 μg/L, t=140.56, P<0.01], all the differences were statistically significant. Subgroup analysis revealed that concentrations of IL-6, IL-1β, IL-10 and TNF-α gradually increased with the advancement of TNM staging (P<0.01). In stage III, concentrations of IL-6, IL-1β, and IL-10 were the highest, TNF-α concentration was the highest in stage IV. RvD1 concentration gradually decreased with the advancement of TNM staging(P<0.01).
CONCLUSIONS
Compared with healthy volunteers, the levels of serum inflammatory cytokines in colon cancer patients increase significantly while the level of RvD1 decreases significantly. Both are associated with higher TNM stage of colon cancer.
Aged
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Colonic Neoplasms
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blood
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immunology
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pathology
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Cytokines
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blood
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Docosahexaenoic Acids
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blood
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Female
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Humans
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Male
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Middle Aged
2.S1000A12, Chitotriosidase, and Resolvin D1 as Potential Biomarkers of Familial Mediterranean Fever.
Ali TAYLAN ; Oguz GURLER ; Burak TOPRAK ; Ali Riza SISMAN ; Hulya YALCIN ; Ayfer COLAK ; Ismail SARI
Journal of Korean Medical Science 2015;30(9):1241-1245
Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterised by periodic inflammatory attacks. We investigated changes in monocyte-granulocyte derived S10012A and chitotriosidase in both the attack and silent period of FMF for better estimation of inflammation. Endogenous resolvin was determined for utility to restrict inflammation. This study included 29 FMF patients (15 M/14 F) and 30 healthy controls (15 M/15 F). Serum levels of highly sensitive C-reactive protein, serum amiloid A (SAA), S100A12, chitotriosidase, and resolvin D1 were measured. Age, sex, body mass indexes, and lipids were similar between patients and controls. Biomarkers including hs-CRP, SAA, S100A12, chitotriosidase, and resolvin D1 were higher in the attack period of FMF patients compared to controls (P < 0.001). When FMF patients in the silent period were compared with their attack period, hs-CRP, SAA, and chitotriosidase were found elevated in the attack period (P < 0.001, P < 0.001, and P = 0.02 respectively). Serum levels of SAA, S100A12, chitotriosidase, and resolvin D1 in the silent period of FMF patients were still found elevated compared to healthy controls, indicating subclinical inflammation (P < 0.001, P < 0.001, P = 0.009, and P < 0.001 respectively ). In subgroup analysis, patients with M694V homozygote and heterozygote mutations had higher S10012A and hs-CRP compared to other mutation carriers. Our findings indicate that chitotriosidase and S10012A are useful in diagnosis and detection of subclinical inflammation and/or assessment of disease activity in FMF patients. They could be more informative for inflammation in various disease states compared to hsCRP and SAA. Resolvin D1 is elevated in both the attack and silent periods of FMF. It may be helpful to restrict inflammation.
Adult
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Biomarkers
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Docosahexaenoic Acids/*blood
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Familial Mediterranean Fever/*blood/*diagnosis
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Feasibility Studies
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Female
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Hexosaminidases/*blood
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Humans
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Male
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Reproducibility of Results
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S100A12 Protein/*blood
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Sensitivity and Specificity
3.Effects of docosahexaenoic acid on inflammation-associated cytokines in blood and pulmonary tissue of rats with severe scald injury.
Jie ZHANG ; Zhengguo XIA ; Xingzhao LI ; Chen CAI ; Qinglian XU
Chinese Journal of Burns 2015;31(1):16-20
OBJECTIVETo observe the effects of docosahexaenoic acid (DHA) on the expressions of TNF-α, IL-6, and leukotriene B4 (LTB4) in serum and expression of NF-κB in pulmonary tissue of rats with severe scald injury.
METHODSOne hundred and sixty SD rats were divided into sham injury (A), sham injury+DHA (B), scald (C), and scald+DHA (D) groups according to the random number table, with 40 rats in each group. Rats in groups A and B were sham injured, while rats in groups C and D were inflicted with 30% TBSA full-thickness scald on the back. Rats in groups B and D were injected with 0.5 mg/mL DHA solution with the dosage of 1 mL/kg via tail vein 5 minutes post injury, while rats in groups A and C with normal saline solution 1 mL/kg. At post injury hour (PIH) 3, 6, 12, 24, and 48, pulmonary tissue and abdominal aorta blood were collected from 8 rats in each group. The serum levels of TNF-α, IL-6, and LTB4 were determined with ELISA, and the protein expression of NF-κB p65 in pulmonary tissue was determined with Western blotting. Data were processed with analysis of variance of factorial design and LSD-t test.
RESULTS(1) The serum levels of TNF-α and IL-6 of rats in group A were similar to those of group B at each time point (with tTNF-α values from 0.223 to 0.947, tIL-6 values from 0.767 to 2.084, P values above 0.05). Compared with those of group A, the serum levels of TNF-α and IL-6 of rats in groups C and D were significantly higher at each time point (with tTNF-α values from 11.800 to 40.357, tIL-6 values from 10.334 to 39.321, P values below 0.01). The serum levels of TNF-α and IL-6 of rats in group D were significantly lower than those of group C at each time point (with tTNF-α values from -17.643 to -8.331, tIL-6 values from -21.596 to -6.332, P values below 0.01). The serum levels of TNF-α and IL-6 in groups C and D both showed a trend of increase earlier and decrease later, and they peaked at PIH 12, respectively (360.4 ± 13.2), (306.8 ± 7.2) pg/mL and (265.4 ± 12.3), (230.5 ± 2.2) pg/mL. (2) The serum level of LTB4 in group A was similar to that of group B at each time point (with t values from 0.787 to 1.096, P values above 0.05). The serum level of LTB4 was significantly higher in groups C and D than in group A at each time point (with t values from 7.501 to 38.962, P values below 0.01). The serum level of LTB4 in group D was obviously lower than that of group C at each time point (with t values from -19.244 to -2.532, P values below 0.01). The serum level of LTB4 in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, (4.59 ± 0.29) and (2.85 ± 0.32) ng/mL respectively. (3) The protein expression of NF-κB p65 in pulmonary tissue in group A was similar to that of group B at each time point (with t values from 0.847 to 1.256, P values above 0.05). The protein expression of NF-κB p65 was significantly higher in groups C and D than in group A at each time point (with t values from 15.167 to 98.074, P values below 0.01). The protein expression of NF-κB p65 in group D was obviously lower than that of group C at each time point (with t values from -37.190 to -14.415, P values below 0.01). The protein expression of NF-κB p65 in groups C and D both showed a trend of increase earlier and decrease later, and it peaked at PIH 12, respectively 4.46 ± 0.12 and 2.94 ± 0.21.
CONCLUSIONSParenteral supply of DHA to rats with severe scald injury can reduce the levels of TNF-α, IL-6, and LTB4 in serum and decrease the expression of NF-κB in pulmonary tissue, thus alleviating the inflammation response.
Animals ; Blotting, Western ; Burns ; Cytokines ; Docosahexaenoic Acids ; Enzyme-Linked Immunosorbent Assay ; Inflammation ; Interleukin-6 ; blood ; Leukotriene B4 ; blood ; Lung ; metabolism ; pathology ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serum ; Soft Tissue Injuries ; Tumor Necrosis Factor-alpha ; blood ; genetics ; Up-Regulation ; physiology
4.Xuebijing Injection () and Resolvin D1 Synergize Regulate Leukocyte Adhesion and Improve Survival Rate in Mice with Sepsis-Induced Lung Injury.
Shu-Kun ZHANG ; Yu-Zhen ZHUO ; Cai-Xia LI ; Lei YANG ; Hong-Wei GAO ; Xi-Mo WANG
Chinese journal of integrative medicine 2018;24(4):272-277
OBJECTIVETo investigate the effect of combined application of Xuebijing Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury.
METHODSThe cecal ligation and puncture (CLP) method was used to develop a mouse sepsis model. Specific pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each): sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 μL/g body weight), RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and RvD1), respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase (MPO) and the expression of intercellular cell adhesion molecule 1 (ICAM-1).
RESULTSCompared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP+XBJ and CLP+RvD1 groups (P<0.05). In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP+XBJ+RvD1 group (P<0.05 or P<0.01).
CONCLUSIONSXBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.
Animals ; CD18 Antigens ; metabolism ; Cell Adhesion ; drug effects ; Docosahexaenoic Acids ; administration & dosage ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Injections ; Intercellular Adhesion Molecule-1 ; metabolism ; Leukocytes ; drug effects ; metabolism ; pathology ; Lung ; drug effects ; enzymology ; pathology ; Lung Injury ; blood ; complications ; drug therapy ; Male ; Mice, Inbred C57BL ; Peroxidase ; metabolism ; Sepsis ; blood ; complications ; drug therapy ; Survival Analysis