Effect of decoy-oligodeoxynucleotides on expression of inflammation mediators in pMΦ cells from rats

Objective: To study the effect of decoy-oligodeoxynucleotides (decoy-ODNs) in dumbbell shape with the oligodeoxynucleotide sequence similar to nuclear factor kappa B (NF-κB) cis-elements on expression of inflammation mediators in pMΦ cells from rats. Methods: With carriers of cationic liposomes, decoy-ODNs were transfected into pMΦ cells of rats. Then the inhibiting effects of the decoy-ODNs on tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and IL-10 were analyzed. Results: Decoy-ODNs could decrease the expression of TNFα and IL-6 in dose-dependent fashion but had weaker inhibiting effect on IL-10. Conclusions: Decoy-ODNs targeting NF-κB can decrease the expression of inflammatory mediators in pMΦ cells from rats.

Genetic predisposition to inflammation:a new risk factor of Alzheimer's disease

Inflammation has been shown to play an important role in the progression of Alzheimer＇s disease （AD）. Recent epidemical study indicates that the incidence of AD in some populations is substantially influenced by the gene polymorphisms of the inflammation mediators. Meanwhile, an ensured risk factor, the ApoE ε4 allele is also reported to directly promote inflammation. Accordingly, it appears that an individual genetic background has partly determined his predisposition for AD by the extent of the inflammation response to the chronic stimulus by β-amyloid peptide （Aβ） deposits and other antigen stressor in the elderly. Hence we present a hypothesis that the inflammation genotypes may contribute to AD susceptibility. This may provide a new orientation both for future identification of individuals at risk and for personalized medication.

Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis

AIM： To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis （AP）, and the influences of artemisinin on them.METHODS： AP was induced by 4 intraperitoneal iojections of caerulein at 1 h intervals. To induce apoptosis, solution of artemisinin （50 mg/kg） was given intraperitoneally 1, 12, 24 and 36 h after the last caerulein injection. Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis. Apoptosis and oncosis were detected with acridine orange （AO） and ethylene dibromide （EB） staining. Caspase-3 and myeloperoxidase （MPO） activity were measured by colorimetric assay. Nuclear factor-kappa B （NF-KB） activation was detected by flow cytometry. Macrophage inflammatory protein-lα（MIP-1α） protein was measured by Western blot. Interleukin- 1β（IL-1β） mRNA was detected by RT-PCR.RESULTS： Addition of artemisinin increased the number of apoptotic cells （11.7%±1.4% vs 6.3%± 0.7%, P 〈 0.05）, while reduced the number of oncotic cells （13.0% ±2.4% vs 17.5%±2.2%, P 〈 0.05）. The activity of caspase-3 speeded up （1.52±0.21 vs 1.03±0.08, P 〈 0.05）, the pancreas pathological impairment was relieved （3.0±0.5 vs 4.0± 0.5, P 〈 0.05） and the level of serum amylase decreased （5642±721 U/dL vs 7821±653 U/dL, P 〈 0.05）. The activation of NF-1α （29%±4.1% vs 42%±5.8%）, MIP-1α protein （3.7±0.5 vs 5.8±0.7）,MPO （0.52±0.06 U/g vs 0.68±0.09 U/g）, IL-1β mRNA （1.7 ±0.3 vs 2.4 ±0.4） in the apoptosis inducing group was obviously decreased （P 〈 0.05）.CONCLUSION： Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats.

Blood glucose control in patients with severe sepsis and septic shock

The main pathophysiological feature of sepsis is the uncontrollable activation of both pro-and anti-inflammatory responses arising from the overwhelming pro-duction of mediators such as pro-and anti-inflammatory cytokines. Such an uncontrollable inflammatory response would cause many kinds of metabolic derangements. One such metabolic derangement is hyperglycemia. Accordingly, control of hyperglycemia in sepsis is considered to be a very effective therapeutic approach. However, despite the initial enthusiasm, recent studies reported that tight glycemic control with intensive insulin therapy failed to show a beneficial effect on mortality of patients with severe sepsis and septic shock. One of the main reasons for this disappointing result is the incidence of harmful hypoglycemia during intensive insulin therapy. Therefore, avoidance of hypoglycemia during intensive insulin therapy may be a key issue in effective tight glycemic control. It is generally accepted that glycemic control aimed at a blood glucose level of 80-100 mg/dL, as initially proposed by van den Berghe, seems to be too tight and that such a level of tight glycemic control puts septic patients at increased risk of hypoglycemia. Therefore, now many researchers suggest less strict glycemic control with a target blood glucose level of 140-180 mg/dL. Also specific targeting of glycemic control in diabetic patients should be considered. Since there is a significantcorrelation between success rate of glycemic control and the degree of hypercytokinemia in septic patients, some countermeasures to hypercytokinemia may be an important aspect of successful glycemic control. Thus, in future, use of an artificial pancreas to avoid hypoglycemia during insulin therapy, special consideration of septic diabetic patients, and control of hypercytokinemia should be considered for more effective glycemic control in patients with severe sepsis and septic shock.

Mechanisms for amplified mediator release from colonic mast cells:Implications for intestinal inflammatory diseases

The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decadest. Some have concluded that the absence of mast cells is incompatible with life, at least in humans, because no human conditions have been documented where these cells are absent from the body. On the other hand, mice harboring specific mutations in certain growth factors, or their receptors, that

Plasma apo CⅢ Levels in Relation to Inflammatory Traits and Metabolic Syndrome in Patients not Treated with Lipid-lowering Drugs Undergoing Coronary Angiography

Objective Assessment of the comprehensive relationship among apolipoprotein CIII（apoCⅢ） levels, inflammation, and metabolic disorders is rare. Methods A total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCⅢ in the association of inflammation with metabolic syndrome（MetS）. Results Patients with MetS showed higher levels of apoCⅢ [95.1（73.1-131.4） vs. 81.7（58.6-112.4） μg/mL, P 〈 0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7（0.8-3.4） vs. 1.1（0.5-2.2） mg/L; white blood cell count,（6.48 ± 1.68） vs.（6.11 ± 1.67） × 10~9/L]. The levels of apoCⅢ and inflammatory markers increased with the number of metabolic risk components（all P 〈 0.001）. Furthermore, apoCⅢ levels were associated with virtually all individual MetS risk factors and inflammatory markers（all P 〈 0.05）. Importantly, the prevalence of MetS in each metabolic disorder rose as apoCⅢ levels increased（all P 〈 0.05）. Mediation analysis showed that apoCⅢ partially mediated the effect of inflammation on MetS independently from triglycerides. Conclusion Plasma apoCⅢ levels were significantly associated with the development and severity of MetS, and a role of apoCⅢ in the effect of inflammation on the development of MetS was identified.

Expression of platelet-endothelial cell adhesion molecule-1 in human umbilical vein endothelial cells by exposure to advanced glycosylation end products and inflammatory mediators

Objective To determine whether advanced glycosylation end products modified bovine serum albumin (AGEs-BSA) affects endothelial cell lateral junction protein, platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the presence or absence of inflammatory mediators.Methods Cultured human umbilical vein endothelial cells (HUVECs) were exposed to AGEs-BSA for 6, 12, 24, and 36 hours, and exposed to AGEs-BSA glycosylated with different concentrations of glucose, tumor necrosis factord-α (TNF-α), interferon (IFN-γ), TNF-α + IFN-y and AGEs-BSA + TNF-α for 24 hours, respectively. Expression of PECAM-1 mRNA was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) with β-actin as an internal standard, and sequencing of RT-PCR products was performed to confirm the specificity of amplification for PECAM-1 gene. The endothelial cell surface expression of PECAM-1 was determined by flow cytometry (FCM).Results There were no significant changes in the expression of PECAM-1 mRNA and protein when the cells were exposed to AGEs-BSA with different concentrations or periods ( P>0. 05). However, PECAM-1 expression was reduced in the cells treated with TNF-α, IFN-y, TNF-α + IFN-γ and AGEs-BSA + TNF-α. The level of PECAM-1 treated with AGEs-BSA + TNF-α was lower than that of TNF-α treated alone (P<0. 01).Conclusions AGEs-BSA had no effect on the expression of PECAM-1 mRNA and protein in cultured HUVEC. With the presence of inflammatory mediator TNF-α, AGEs-BSA decreased the level of PECAM-1, which might reduce the adhesion interaction between adjacent endothelial cells, enhance the permeability of endothelial cells, and might be implicated in the endothelial dysfunction and pathogenesis of atherosclerosis in patients with diabetes mellitus. The significance of this phenomenon in intracellular signal transduction remains to be determined.

Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats

Background It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis, so blocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis. We studied the regulatory effect of arsenic trioxide （As2O3） on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and its therapeutic effect on acute pancreatitis. Methods Pancreatic acinar cells were isolated by collagenase digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were detected with Hoechst 33258＋PI or Annexin V＋PI double fluorescent staining. Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor α （TNF-α） mRNA, myeloperoxidase, nuclear factor-κB and histological grading of pancreatic damage were measured.Results There was an increased apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment with AS2O3. The levels of lactate dehydrogenase and amylase release were markedly decreased in As2O3 treated group. Myeloperoxidase content, TNF-α mRNA level, nuclear factor-κB activation and pathological score in As2O3 treated group were significantly lower than in the untreated group. Conclusions As2O3 can induce apoptosis and reduce oncosis of pancreatic acinar cell, thus resulting in reduced release of endocellular enzyme of acinar cells, reduced inflammatory cell infiltration and decreased the production of inflammatory cytokines, so that the outcome of alleviated pathological changes was finally achieved.

Clinical study of inflammatory factors in sputum induced early after lung volume reduction surgery

Background The aim of this study was to prospectively study the changes in neutrophil elastase （NE）, fibroblast growth factor 9 （Fgf9）, matrix metalloproteinase-9 （MMP-9）, tissue inhibitor of metalloproteinase 1 （TIMP-1） in sputum induced during the early period after lung volume reduction surgery （LVRS）. Methods From April to October 2005, ten consecutive patients with chronic obstructive pulmonary disease （COPD） underwent LVRS. Ten non-small cell lung cancer patients （stage II-Illa） received Iobectomy as a control group. The induced sputum was collected from both groups at six different times （two weeks before operation and postoperatively at 1, 2, 4, 6 and 10 days）. The level of NE, Fgf9, MMP-9 and TIMP-1 were measured using enzyme-linked immunosorbent assay. Results The pulmonary function （FEV~%） and arterial blood gases （PaO2 and PaCO2） were significantly different belween the groups. There were no significant differences in age, ejection fraction （EF）, and operation duration, but hemoglobin in the LVRS group was statistically higher than in the controls. At certain times, there were significant differences in NE, MMP-9, TIMP-1 and MMP-9/TIMP-1 （P 〈0.05） but not in Fgf9 between the two groups. The levels of NE and TIMP-1 were maximal at 2 days postoperatively and that of MMP-9 and MMP-9/TIMP-1 at 4 days postoperatively in the LVRS group. In the control group, maximal levels of NE and TIMP-1 occurred at 2 days postoperatively and that of MMP-9 and MMP-9/TIMP-1 at 1 day postoperatively. Ten days after surgery, all values of the control group were not significantly different from the baseline. In the LVRS group, the levels were significantly different from the pre-operative values （P 〈0.05） apart from TIMP-1. Conclusion The levels of NE, MMP-9, TIMP-1 and MMP-9/TIMP-1 of the LVRS group were different from those of the control group. The time course of these chanties may be related to LVRS and the underlying process of COPD.

Association between Plasma Leptin Level and Systemic Inflammatory Markers in Patients with Aggressive Periodontitis

Background：Increasing evidence supports an association between periodontitis and systemic diseases.Leptin is involved both in the energy metabolism and inflammatory processes and is suggested to be a link between periodontal infection and systemic health.The present study aimed to evaluate the peripheral leptin concentration in patients with aggressive periodontitis （AgP） and to explore the relationship between leptin and systemic inflammation.Methods：Ninety patients with AgP visiting the Clinic of the Periodontology Department,Peking University School and Hospital of Stomatology between July 2001 and May 2006,and 44 healthy controls （staffand student volunteers in the same institute） were recruited.Plasma levels of leptin and inflammatory cytokines including interleukin （IL）-1β,I L-6,tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP） were measured by enzyme-linked immunosorbent assay.Correlation and multiple linear regression analysis were performed to analyze the association between plasma leptin level and other variables.Results：Plasma leptin level of AgP group was significantly higher than that of the control group （19.7-4.4 ng/ml vs.7.5 ± 1.3 ng/ml,P ＜ 0.01）.After controlling for age,gender,and body mass index,positive correlation was observed between plasma leptin concentration and log-transformed levels of pro-inflammatory cytokines （IL-1β,IL-6,TNF-α and CRP）,and the partial correlation coefficients ranged from 0.199 to 0.376 （P ＜ 0.05）.Log-transformed IL-1β and I L-6 levels entered the final regression model （standardized β were 0.422 and 0.461 respectively,P ＜ 0.01）.Conclusions：Elevated plasma leptin concentration may be associated with increased systemic levels of inflammatory markers in AgP patients.

Anti-inflammatory and analgesic effects of Yaotuitong Capsules in experimental rats with chemically induced radicular neuritis

OBJECTIVE:The aims of this study were to determine the anti-inflammatory and analgesic effects of Yaotuitong(translation:low back and leg pain) capsules,a Chinese herbal preparation,and the histological changes it induces in experimental rats with chemically induced radicular neuritis.METHODS:Wistar rats were randomly divided into normal,model,Western medicine,and traditional Chinese medicine groups(n=24 per group).We surgically duplicated a chemical radicular neuritis model to simulate lumbar intervertebral disc protrusion.Granuloma formation was measured on postoperative days(PODs) 3,7,14,and 21.Prostaglandin E 2 and 5-hydroxytryptamine(inflammation mediators) levels in the surrounding tissue and the histology of the nerve root were determined on PODs 7 and 14.RESULTS:Yaotuitong capsules significantly reduced prostaglandin E 2(P<0.01) and 5-hydroxytryptamine(P<0.01)levels in tissue surrounding the nerve root.It also inhibited granuloma formation(P<0.05).CONCLUSION:Yaotuitong capsules have anti-in-flammatory and analgesic effects that can alleviate the discomfort of lumbar intervertebral disc protrusion.