The main eicosanoids inflammatory mediators, prostaglandins and leukotrienes, are both generated from arachidonic acid (AA; 20:4 n-6). AA is a member of polyunsaturated fatty acids (PUFAs). Numerous studies have demonstrated that various contents of PUFAs can modulate the inflammatory responses. However, fewer studies have examined n-9PUFAs and their effects on the inflammatory responses. In the present study, the role of 5,8,11-cis-eicosatrienoic acid (ETrA; 20:3 n-9, also called Mead acid) in the inflammatory responses has been investigated. The anti-inflammatory activities of ETrA were examined using an in vitro macrophage system and the inhibitory effect was confirmed by western blot analysis for iNOS and COX-2 expressions. The interactions between ETrA and COX-2 protein were simulated to produce a computer modeling protein-ligand complexes and the results suggest a possible mechanism for the effects of ETrA. In this study, we described a significant inhibition of the inflammatory activities initiated by ETrA. Since ETrA is a substance presented in the tissues of young animals, we therefore anticipate that ETrA can be utilized as a natural therapeutic supplement to inhibit inflammatory activities.
Tumor metastasis is a major cause of death of patients with colorectal cancer (CRC). Our previous findings show that adenine has antiproliferation activity against tumor cells. However, whether adenine reduces the invasiveness of DLD-1 and SW480 CRC cells has not been thoroughly explored. In this study, we aimed to explore the effects of adenine on the invasion potential of DLD-1 cells. Our findings showed that adenine at concentrations of ≤200 μM did not influence the cell viability of DLD-1 and SW480 CRC cells. By contrast, adenine reduced the migratory potential of the CRC cells. Moreover, it decreased the invasion capacity of the CRC cells in a dose-dependent manner. We further observed that adenine downregulated the protein levels of tissue plasminogen activator, matrix metalloproteinase-9, Snail, TWIST, and vimentin, but upregulated the tissue inhibitor of metalloproteinase-1 expression in DLD-1 cells. Adenine decreased the integrin αV level and reduced the activation of integrin-associated signaling components, including focal adhesion kinase (FAK), paxillin, and Src in DLD-1 cells. Further observations showed that adenine induced AMP-activated protein kinase (AMPK) activation and inhibited mTOR phosphorylation in DLD-1 cells. The knockdown of AMPK restored the reduced integrin αV level and FAK/paxillin/Src signaling inhibited by adenine in DLD-1 cells. Collectively, these findings reveal that adenine reduces the invasion potential of DLD-1 cells through the AMPK/integrin/FAK axis, suggesting that adenine may have anti-metastatic potential in CRC cells.
Prostate specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). Recently, proPSAs, comprised of native proPSA, as well as truncated proPSA forms, [-2] proPSA, [-5] proPSA, and [-7] proPSA, have been shown to be better diagnostic targets than PSA for PCa. Stable isotope labeling-multiple reaction monitoring mass spectrometry (SIL/MRM-MS) has been frequently used to measure low-abundance biomarkers in tissues and biofluids, owing to its high sensitivity and specificity, simplicity, and multiplexing capability. In this study, we have developed and optimized a strategy using immunoprecipitation in conjunction with SIL/MRM-MS assay which is capable of sensitive and accurate quantification of proPSA in serum. Since serum and plasma are by far the most complex biological fluids, the immunoprecipitation workflow was optimized to achieve sufficient sensitivity, efficiencies of protein purification with immunoaffinity depletion were determined. The developed strategy can detect proPSA and PSA with a limit of detection (LOD) and limit of quantitation (LOQ) at nanogram per milliliter levels, corresponding to a concentration 6 orders-of-magnitude lower than the most abundant serum proteins. Furthermore, the simultaneous measurement of multiple biomarkers, including the mature and precursor forms of PSA, can be achieved in a single multiplexed analysis using LC/MRM-MS. The strategy demonstrated here provides an attractive alternative to ELISAs or RIAs for the reliably measurement of proPSA to improve the specificity of PCa diagnosis.
There are many kinds of therapies for acute cerebral infarction,Now the most effective therapy is thrombolysis by vessel,while the therapy including anti-platelet aggregation,fibrin-decreasing,anti-coagulation and cerebral protection in the patients passing its super early phase has the same importance.Scaffold implantation is the hot spot in current study.To explore effective methods is very important.This disease needs individualized therapy based on grouping and staging.The emphasis should be put on the therapy of its acute phase.This article reviews therapeutic progress and typing of acute cerebral infarction in domestic and abroad recent years.
Objective To investigate the application value of methylene blue excretion test in early reasonable nutritional support for severe traumatic brain injury.Methods One hundred and thirty-three cases of severe traumatic brain injury admitted to hospital from January 2010 to June 2012 were chosen as treatment group,while the 127 cases of similar patients admitted to hospital from January 2007 to December 2009 were chosen as control group.Patients in treatment group underwent methylene blue excretion test in 3 days,8 days,15 days after injury,and the nutritional support ways were determined according to the elimination time of methylene blue in patients' urine.The control group conventionally receive enteral nutrition support therapy firstly,after 15 days if they still cannot be tolerant of the enteral nutrition,then parenteral nutrition therapy were adopted.The weight,serum albumin and hemoglobin circumstances of the two groups were determined and the complications were recorded.Glasgow coma score (GCS) of 3 months after injury were followed up.Results There was no significant difference on the average body weigh between these two groups before treatment.The average body weight of the treatment group was significantly higher than that of control group after 3 months treatment((56.3 ± 5.5) kg vs.(52.6 ± 5.3) kg,t =5.93,P ＜ 0.01).The serum albumin and hemoglobin of 14 d,21 d after injury were significantly higher than those of the control group (serum albumin of 14 d:(32.7 ±3.4) g/L vs.(28.8 ±3.1) g/L; serum albumin of 21 d:(34.3 ±3.8) g/L vs.(30.7 ±3.3) g/L;hemoglobin of 14 d:(113.4±12.5) g/L vs.(102.2 ±11.6) g/L;hemoglobin of 21 d:(118.5 ±13.3) g/L vs.(106.7 ± 12.4) g/L.Nutritional status of treatment group was significantly better than that of the control groupall P ＜ 0.05).After three months,the effective rate of treatment group (93.23％ (124/133)) was significantly higher than that of the control group (84.25％ (107/127)),the difference was statistically significant (x2 =5.29,P ＜ 0.05).Conclusion Determining the early reasonable nutrition support ways for patients with severe traumatic brain injury according to the elimination time of methylene blue in the urine,can provide comprehensive nutrition to patients,enhance their body resistance,reduce the incidence of complications,and create an important clinical value for improving prognosis.
Key words:
Severe traumatic brain injury; Methylene blue excretion test; Enteral nutrition; Parenteral nutrition
The AMP-activated protein kinase (AMPK) signaling system plays a key role in cellular stress by repressing the inflammatory responses induced by the nuclear factor-kappa B (NF-κB) system. Previous studies suggest that the anti-inflammatory role of AMPK involves activation by adenine, but the mechanism that allows adenine to produce these effects has not yet been elucidated. In human umbilical vein endothelial cells (HUVECs), adenine was observed to induce the phosphorylation of AMPK in both a time- and dose-dependent manner as well as its downstream target acetyl Co-A carboxylase (ACC). Adenine also attenuated NF-κB targeting of gene expression in a dose-dependent manner and decreased monocyte adhesion to HUVECs following tumor necrosis factor (TNF-α) treatment. The short hairpin RNA (shRNA) against AMPK α1 in HUVECs attenuated the adenine-induced inhibition of NF-κB activation in response to TNF-α, thereby suggesting that the anti-inflammatory role of adenine is mediated by AMPK. Following the knockdown of adenosyl phosphoribosyl transferase (APRT) in HUVECs, adenine supplementation failed to induce the phosphorylation of AMPK and ACC. Similarly, the expression of a shRNA against APRT nullified the anti-inflammatory effects of adenine in HUVECs. These results suggested that the role of adenine as an AMPK activator is related to catabolism by APRT, which increases the cellular AMP levels to activate AMPK.
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