Aspirin ; pharmacology ; Drug Resistance ; Humans

Aspirin is the most classic anti-platelet drug, plays its important role in preventing and treating cardio- and cerebro-vascular diseases for its excellent potency ratio; however, there exists individual difference in its anti-platelet effect, aspirin resistance (AR) presented in about 25%-40% of patients, which seriously influences the intervention effect of aspirin. So AR has become a clinical problem that attached more attention. In this paper, the authors put forward a new thinking for clinical studying and inventing new effective Chinese drugs on AR by means of screen out AR suffered from cardio/cerebro-vascular patients long-term received aspirin; find their gene difference sites from MtSNP to establish a foundation for AR predication and reasonable strategy formation; meantime, through platelet intervention in vitro adopting uniform design optimization method to explore the best compatibility and matching relationship of anti-platelet Chinese medicine for AR prevention and treatment, so as to fully display the multi-target intervening effects of Chinese drug-therapy.
Aspirin ; pharmacology ; Drug Resistance ; Humans ; Integrative Medicine ; methods ; Platelet Aggregation Inhibitors ; pharmacology ; Research Design

This paper aims to discuss the potential targets,pathways and possible mechanisms of Danhong Injection in treatment of aspirin resistance by using network pharmacology concept and network analysis technique. Active ingredients and potential targets of Danhong Injection were collected from TCMSP database and the ingredients were further screened based on their topological characteristics. The active ingredients with nodal degree of freedom≥9 were selected as the main active ingredients. Targets related to aspirin resistance were collected from Genecards database. Drug-active ingredient-target-disease network was constructed by using Cytoscape3. 7. 0,and Funrich 3. 1. 3 software was used for gene enrichment analysis. Sixty main active ingredients were screened out from 110 active ingredients of Danhong Injection,including 51 ingredients in Salviae Miltiorrhizae Radix et Rhizoma and 11 ingredients in Carthami Flos,2 of which were both in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. In addition,159 potential targets were collected. The results of gene enrichment analysis showed that Danhong Injection could improve aspirin resistance mainly through21 pathways involving coagulation process,inflammatory response and metabolism. This study revealed the effects of Danhong Injection for improving aspirin resistance in multi-component,multi-target and multi-pathway means mainly through regulation in coagulation process,inflammatory response and metabolism,providing more abundant information and basis for subsequent research and experimental work.
Aspirin ; pharmacology ; Drug Resistance ; Drugs, Chinese Herbal ; pharmacology ; Medicine, Chinese Traditional ; Rhizome

This study was conducted to evaluate the growth and NAG-1 gene expression effected by Non-steroidal anti-inflammatory drug (NSAID) on colon cancer cell lines in vitro. The proliferation of colon cancer cells were determined by MTT assay and COX-2 protein expression were detected by Western blot. Total RNA was isolated from three kinds of colon cancer cell lines; the expressions of NAG-1 mRNA in the cells treated with or without NSAIDs were assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. Celecoxib, meloxicam and aspirin were able to inhibit the growth of HT-29, SW480 and LS174-T cells in dose-dependent manner. COX-2 protein expressed in HT-29 and LS174-T, but not in SW480 cells. All of colon cancer cells expressed NAG-1 gene and the level of LS174-T was lower than that of the other two cell lines. NAG-1 expression was increased by treatment with some NSAIDs in all three kinds of colon cancer cells. NSAIDs were able to potentially inhibit the growth of colon cell lines. Induction of NAG-1 gene expression by NSAID was not consistent with COX-2 expression.
Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Aspirin ; pharmacology ; Celecoxib ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; metabolism ; Gene Expression Regulation, Neoplastic ; HT29 Cells ; Humans ; Neoplasm Proteins ; metabolism ; Pyrazoles ; pharmacology ; RNA, Messenger ; metabolism ; Sulfonamides ; pharmacology ; Thiazines ; pharmacology ; Thiazoles ; pharmacology

Aspirin ; pharmacology ; Drug Resistance ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Integrative Medicine ; Medicine, Chinese Traditional ; methods ; Phytotherapy

BACKGROUND: Aspirin is the most common drug used for the prevention of arterial thrombosis. However, platelet responsiveness to aspirin is variable among individuals and it is important to detect aspirin resistance to improve clinical outcome. We analyzed the changes of platelet reactivity before and after aspirin treatment. We also investigated the incidence and influencing factors of aspirin resistance in Korean. METHODS: We tested platelet function in 198 patients who had been treated with aspirin in a Korean university hospital, and 59 of these patients were tested for platelet function before and after aspirin treatment. We also analyzed platelet reactivity in 136 patients who had not been treated with aspirin. Platelet function was tested using the VerifyNow Aspirin Assay (Accumetrics, USA). Platelet reactivity was expressed as aspirin reaction unit (ARU) and > or =550 ARU was defined as aspirin resistance. RESULTS: Platelet reactivity of 136 patients who had not been treated with aspirin was 632.2+/-46.3 ARU (mean+/-SD) (range, 462-675). Platelet reactivity of 198 patients who had been treated with aspirin was 472.5+/-60.0 (338-666) ARU, and 10.1% of patients were aspirin-resistant. The difference of platelet reactivity before and after aspirin treatment was 128.3+/-68.7 (-40-248) ARU. Hb level was lower and platelet count was higher in aspirin-resistant group than in aspirin-sensitive group (P<0.05). CONCLUSIONS: We demonstrated the distribution of platelet reactivity before and after aspirin treatment using the VerifyNow Aspirin Assay. The incidence of aspirin resistance was 10.1%, and low Hb level and high platelet count were related with aspirin resistance.
Aged ; Aspirin/pharmacology/*therapeutic use ; Drug Resistance ; Female ; Hospitals, University ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/pharmacology/*therapeutic use ; Platelet Function Tests ; Predictive Value of Tests

PURPOSE: The purpose of this study is to investigate the mechanism of cellular proliferation of electromagnetic field (EMF) on human intervertebral disc (IVD) cells. MATERIALS AND METHODS: Human IVD cells were cultured three-dimensionally in alginate beads. EMF was exposed to IVD cells with 650Omega, 1.8 millitesla magnetic flux density, 60 Hz sinusoidal wave. Cultures were divided into a control and EMF group. Cytotoxicity, DNA synthesis and proteoglycan synthesis were measured by MTT assay, [3H]-thymidine, and [35S]-sulfate incorporation. To detect phenotypical expression, reverse transcription-polymerase chain reactions (RT-PCR) were performed for aggrecan, collagen type I, and type II mRNA expression. To assess action mechanism of EMF, IVD cells were exposed to EMF with NG-Monomethyl-L-arginine (NMMA) and acetylsalicylic acid (ASA). RESULTS: There was no cytotoxicity in IVD cells with the EMF group in MTT assay. Cellular proliferation was observed in the EMF group (p < 0.05). There was no difference in newly synthesized proteoglycan normalized by DNA synthesis between the EMF group and the control. Cultures with EMF showed no significant change in the expression of aggrecan, type I, and type II collagen mRNA compared to the control group. Cultures with NMMA (blocker of nitric oxide) or ASA (blocker of prostaglandin E2) exposed to EMF demonstrated decreased DNA synthesis compared to control cultures without NMMA or ASA (p < 0.05). CONCLUSION: EMF stimulated DNA synthesis in human IVD cells while no significant effect on proteoglycan synthesis and chondrogenic phenotype expressions. DNA synthesis was partially mediated by nitric oxide and prostaglandin E2. EMF can be utilized to stimulate proliferation of IVD cells, which may provide efficient cell amplification in cell therapy to degenerative disc disease.
Adult ; Aspirin/pharmacology ; Cell Proliferation/*radiation effects ; Collagen/metabolism ; Dinoprostone/metabolism ; *Electromagnetic Fields ; Enzyme Inhibitors/pharmacology ; Female ; Humans ; Intervertebral Disk/*pathology/radiation effects ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Tetrazolium Salts/pharmacology ; Thiazoles/pharmacology ; omega-N-Methylarginine/pharmacology

OBJECTIVETo observe the anti-tumor effect of combination TNF-related apoptosis-inducing ligand (TRAIL) with aspirin on liver cancer cell line, SMMC-7721.

METHODSThe survival fraction of SMMC-7721 cells was measured by MTT assay, apoptosis rate and cell cycle was determined by flow cytometry, and the expression of apoptosis-related gene was identified by western blot.

RESULTSThe survival fraction of SMMC-7721 cells treated with 300 ng/ml TRAIL, 3 mmol/L or 10 mmol/L aspirin alone was 82.76%, 81.34% and 71.29% respectively, and the survival fractions of SMMC-7721 cells treated with TRAIL and 3 mmol/L or 10 mmol/L aspirin were 43.54% and 37.8% respectively. The apoptosis rates of SMMC-7721 cells induced by TRAIL and 3 mmol/L or 10 mmol/L aspirin were higher than that induced by TRAIL or aspirin alone (34.76% and 38.56% vs 21.25%, 1.89% and 6.08%), and G0/G1 arrest was observed under TRAIL and aspirin. The expression of Bcl-2 in SMMC-7721 cells treated by 3 mmol/L or 10 mmol/L aspirin decreased markedly, but no effect on Bax.

CONCLUSIONThe cooperative anti-tumor effect of aspirin and TRAIL may be related to the inhibition of the expression of Bcl-2 by aspirin

Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; Aspirin ; pharmacology ; Cell Survival ; drug effects ; Humans ; Membrane Glycoproteins ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha ; pharmacology

OBJECTIVETo evaluate the effects of aspirin, clopidogrel, and their combination on the progression of aortic atherosclerosis.

METHODSForty-nine male rabbits were randomly divided into five groups. One group of control rabbits (group N, n=9) was fed on normal diets. Four other groups were fed on high cholesterol diets and injected with 10% albumin bovine received no drug therapy (group M, n=10), aspirin (group A, n=10), clopidogrel (group C, n=10), or the combination (aspirin+clopidogrel, group B, n=10) for 12 weeks. Serum lipids and C-reactive protein (CRP) were detected. The aortas were harvested for histomorphometry and quantitative analysis. The positive percentage of macrophage cells and smooth muscle cells in the plaque were analyzed by immunohistochemistry.

RESULTSThese antiplatelet drugs significantly reduced the extent of atherosclerosis. Aortic vascular lesions of group A, C, and B showed 28.70%, 28.82%, and 57.69% of reduction in the amount of macrophage cells, and 39.86%, 42.60%, and 100.70% of increase in smooth muscle cells. No significant differences existed between group A and group C. However, the combination of aspirin and clopidogrel had better effect than aspirin or clopidogrel alone. Meanwhile, aspirin, clopidogrel, and their combination also decreased serum CRP (P < 0.05-0.01), without affecting lipid levels. There was a trend, not significantly, to lower serum C-reactive protein in group B compared with group A or group C.

CONCLUSIONSAspirin and clopidogrel inhibit neointimal proliferation and prevent the development of atherosclerosis with equivalent effects. Their combination shows synergic effects.

Animals ; Aorta ; pathology ; Aspirin ; pharmacology ; Atherosclerosis ; blood ; pathology ; C-Reactive Protein ; metabolism ; Cell Count ; Cyclooxygenase Inhibitors ; pharmacology ; Drug Synergism ; Macrophages ; drug effects ; Male ; Myocytes, Smooth Muscle ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rabbits ; Random Allocation ; Ticlopidine ; analogs & derivatives ; pharmacology

OBJECTIVE: To explore the impact of sitagliptin on aspirin resistance (AR) in patients with Type 2 diabetes mellitus (T2DM).
 METHODS: A total of 68 cases of AR were chosen from 136 cases of T2DM patients. The clinical data, including blood samples, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), and high sensitive C reactive protein (hs-CRP) were collected. Aenosine diphosphate (ADP) and arachidonic acid (AA) -induced platelet aggregation rate (PAG) were detected in 1, 3, 6 and 12 months after the treatment to evaluate the impact of sitagliptin on AR. 
 RESULTS: After 6 months of hypoglycemic treatment, FPG and HbAlc in two groups were at the normal level. The hypoglycemic effect was not obviously different (P>0.05), but the hsCRP and ADP or AA-induced PAG were decreased in the sitagliptin group with statistical significance when compared with the metformin group (P<0.05).
 CONCLUSION Sitagliptin can significantly improve the oxidative stress inflammatory state in T2DM patients and AR, which is independent on blood glucose control.
Aspirin ; pharmacology ; Blood Glucose ; analysis ; C-Reactive Protein ; analysis ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Resistance ; Glycated Hemoglobin A ; analysis ; Humans ; Hypoglycemic Agents ; pharmacology ; Metformin ; pharmacology ; Oxidative Stress ; Sitagliptin Phosphate ; pharmacology