The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Anti-Inflammatory Agents ; therapeutic use ; Biomarkers, Pharmacological ; Cardiovascular Diseases ; drug therapy ; enzymology ; immunology ; Cyclooxygenase 2 ; immunology ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; immunology ; Reactive Oxygen Species ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Adult ; Chemical and Drug Induced Liver Injury, Chronic ; Dimethylformamide ; poisoning ; Female ; Humans

Comorbidity ; Humans

Objective To evaluate the effect of hydrogen-rich saline on the expression of phosphor-p38 mitogen-activated protein kinase (p-p38MAPK) during cerebral ischemia-reperfusion (I/R) in rats.Methods Seventy-two adult male Sprague-Dawley rats,weighing 220-250 g,were randomly divided into 3 groups (n =20 each) using a random number table:sham operation group (group S),I/R group and hydrogen-rich saline group (group I/RH).Cerebral ischemia was induced in chloral hydrate-anesthetized rats by 2 h middle cerebral artery occlusion in I/R and I/RH groups.The artery was only exposed but not occluded in group S.At 3 days before operation and immediately after onset of reperfusion,hydrogen-rich saline (0.6 mmol/L) 10 ml/kg was intraperitoneally injected in group I/RH,while the equal volume of normal saline was given in S and I/R groups.Neurological deficits were blindly assessed and scored at the end of 24 h reperfusion.The animals were then sacrificed,and brains were removed for microscopic examination and for determination of the cerebral infarct size (by TTC),brain water content,cell apoptosis (by TUNEL),and expression of p38MAPk and phosphor-p38MAPK (p-p38MAPK) (by immunohistochemistry and Western blot).Apoptosis index was calculated.Results Compared with group S,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly increased,and the expression of p38MAPK and p-p38MAPK was up-regulated in I/R and I/RH groups.Compared with group I/R,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly decreased,and the expression of p38MAPK and p-p38MAPK was down-regulated in group I/RH.The pathological changes of cerebral tissues were significantly attenuated in group I/RH as compared with group I/R.Conclusion Hydrogen-rich saline can reduce cell apoptosis through inhibiting p-p38MAPK expression,thus attenuating cerebral I/R injury in rats.

Objective To investigate the effect of dexamethasone combined with oridonin on proliferation and apoptosis in multiple myeloma cells U266 and the related molecular mechanism. Methods Exponential phase of growth U266 cells were treated with different concentrations of oridonin combined with dexamethasone or alone. U266 cells treated by DMSO were taken as control group. The proliferation inhibitory ratios were measured by CCK-8 assay followed by 24 h, 48 h and 72 h. Apoptosis induction was assessed by using Annexin V-FITC kit. Real time PCR was used to examine the mRNA changes of Notch1, NF-κB/p65 and bcl-2. Western blot assay was applied to detect the protein expression of Notch1, cleaved Notch1, NF-κB/p65 and bcl-2. Results Compared with that in control group, proliferation in all the experimental groups was inhibited (P<0.05), and the apoptosis was promoted (P<0.05); especially the combination of dexamethasone and oridonin had a synergistic effect on the proliferation and apoptosis of U266 cells (P<0.05). The results of PCR and Western blot showed that after treatment of U266 cells with dexamethasone, the mRNA as well as their protein levels of NF-κB/p65 and bcl-2 were decreased compared with those in the control group (P<0.05). Moreover, the mRNA and protein expression of Notch1, cleaved Notch1, NF-κB/p65 and bcl-2 was obviously down-regulated in oridonin group and the combination group (P<0.05). Conclusion Combination of dexamethasone and oridonin can significantly increase the anti-tumor effect by inhibiting proliferation and inducing apoptosis of U266 cells, which may be related to the inhibition of the Notch1 pathway.

Eighty-five endophytic fungal strains were isolated from the roots、stems and leaves of Polygala tenuifolia Willd, among which, fifty-two from natural plants and thirty-three from cultivated ones. Sev-enty-six strains were classified as twenty-three fungal genera. The inhibitory activity screening to fourteen microbe were conducted research. The results showed that some endophytic fungi had remarkble inhibitory activities to Bacillus subtilis, Shigella sonnei, Escherichia coli, Candida albicans, Fusarium kyrushuense and they were all belonged to Fusarium, Alternaria, Aphanocladium respectively. All of the endophytic fungi isolated from Polygala tenuifolia showed no inhibitory activities to Staphyloccocus aureus, Salmonel-lae enteritis, Bibrio parahemolyticus.

OBJECTIVE: To study the effect of Boschniakia rossica extract on free radicals in the brain of D-galactose induced senile rats. METHODS: Sixty Wistar rats were randomly divided into normal group, model group (48 mg.kg(-1).d(-1) D-galactose, SC), Boschniakia rossica group (100, 150, 200 mg/kg ig and 48 mg.kg(-1).d(-1) D-galactose, SC). After 40 days, the activities of SOD, MAO and the content of MDA were measured with colorimetric method, and the histological changes were synchronously observed by electronic microscope. RESULTS: Boschniakia rossica extract significantly increased the SOD activity, decreased the MDA content, and inhibited the MAO activity in the brain tissue. It was observed under microscope that Boschniakia rossica extract could retrieve the degeneration of mitochondrion. CONCLUSION: Boschniakia rossica extract can clear the free radicals for D-galactose induced senile rats.

Objective To evaluate the effect of hydrogen on the activation of caspase-3 in brain tissues during cerebral ischemia-reperfusion (I/R) in rats.Methods Thirty-six healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 3 groups (n=12 each) using a random number table:sham operation (group S),I/R group and hydrogen group (group H).Cerebral ischemia was induced by occlusion of the middle cerebral artery followed by reperfusion in I/R and H groups.In group H,hydrogen-rich saline 5 ml/kg (0.6 mmol/L) was injected intraperitoneally at 3 days before establishment of the model and immediately after the onset of reperfusion.At 24 h of reperfusion,the rats were sacrificed,and hippocampal tissues were obtained for determination of neuroapoptosis (by TUNEL),apoptotic neuron count and expression of activated caspase-3 (by Western blot).The brain tissues in the ischemic area were obtained and stained with haematoxylin and eosin for examination of the pathological changes.Results Compared with group S,the expression of activated caspase-3 was significantly up-regulated,and the apoptotic neuron count was increased in I/R and H groups (P<0.05).Compared with group I/R,the expression of activated caspase-3 was significantly down-regulated,the apoptotic neuron count was decreased (P<0.05),and the pathological changes of brain tissues were significantly reduced in group H.Conclusion The mechanism by which hydrogen inhibits neuroapoptosis during cerebral I/R is probably related to inhibited activation of caspase-3 in brain tissues of rats.

OBJECTIVETo investigate the effect of component I from agkistrodon acutus venomon (AAVC-I) the migration of human umbilical vein endothelial cells (HUVECs), and to elucidate the possible anti-angiogenic mechanism of AAVC-I.

METHODSThe effect of AAVC-I on the migration of HUVECs which was cultivated in vitro and treated with AAVC-1 at four concentrations: 0, 20, 40, 80 microg/ml, was observed by methods of scratch wound-healing and Transwell assay. The expression level of mRNA and protein of P-selectin and intercellular cell adhension molecule-I (ICAM-1) were examined by RT-PCR and Western blot assay.

RESULTSCompared with the blank group, the migration ability of HUVECs in each AAVE-I treated group was reduced in a dose-dependent manner, and the expression level of the mRNA and protein of P-selectin and ICAM-1 were decreased.

CONCLUSIONAAVC-I inhibits the migration of endothelial cell, which is acted by down-regulation of the expression content of mRNA and protein of P-selectin and ICAM-1.

Cell Movement ; drug effects ; Cells, Cultured ; Crotalid Venoms ; pharmacology ; Down-Regulation ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; P-Selectin ; metabolism ; RNA, Messenger

Objective To investigate the plasma vitamin D3 level and its association with B cell subsets of patients with primary Sj(o)gren's syndrome (pSS).The role of vitamin D3 levels in the pathogenesis of pSS was explored.Methods The expression of plasma vitamin D3 levels of 55 patients with pSS and 32 controls were analyzed by ELISA.Frequencies of peripheral blood CD19+CD27-na(i)ve B cells,CD19+CD27+ memory B cells and CD19+CD27high plasma cells were analyzed by flow cytometry in 34 pSS patients without therapy and 22 controls.The relationship between the vitamin D3 levels and B cell subsets,SSDAI,tear flow rate,saliva flow rate,rheumatoid factor,immunoglobulin was analyzed in pSS patients.Non-parametric test,t test,one-way ANOVA,x2test,Pearman's and Spearman's correlation analysis were used for statistical analysis.Results ① There was significant difference in the levels of plasma 1,25 (OH)2D3 between the pSS patients group and normal control group,1,25 (OH)2D3 was significantly lower in pSS patients than that in the normal control group [24.17(22.20,28.41) pg/ml and 41.25(23.38,62.18) pg/ml,P＜0.05],and that was also obviously lower in the active group [22.64(20.74,24.90) pg/ml] than that in the normal control group (P＜0.05),and that was also obviously lower in the active disease group than that in the inactive disease group [25.39 (23.16,33.09) pg/ml,P＜0.05],but there was no difference between the inactive group and the normal control group (P＞0.05).② The percentage of peripheral blood of CD19+CD27high plasma cells and CD19+CD27+ memory B cells in CD19+ cells was reduced in patients in the pSS group compared with the control group [(0.89±0.30)％ and (1.72±0.43)％,(24±8)％ and (34±5)％; P＜0.05],and that was also significantly lower in the active group [(1.03±0.59) ％ ; (26± 10)％] and inactive group [(1.00±0.16)％,(26± 3)％] than that in the normal controls (P＜0.05).However,there was no difference between the active group and the inactive group (P＞0.05),but the frequency of peripheral blood of CD19+ CD27-naive B cells in CD19+ B cells was increased in patients with pSS compared with normal control group [(75.4±7.5)％ and (63.9±5.2)％,P＜0.05],and that was also significantly higher in the active group [(73.4±9.7)％] and inactive group [(73.3±2.9)％] than that in the normal control (P＜0.05),there was no difference between the active group and the inactive group.③ Significant negative correlation was observed between 1,25 (OH)2D3 and the percentage of peripheral blood CD19+CD27+ memory B cells in CD19+ cells as well as immunoglobulin G(r=-0.627,P=0.039; r=-0.657,P＜0.01) level.Conclusions These results demonstrate that abnormality of vitamin D levels may play an important role in the pathogenesis of pSS.