Thromboxane A2 receptor antagonist SQ29548 attenuates SH­SY5Y neuroblastoma cell impairments induced by oxidative stress.

Thromboxane A2 receptor (TXA2R) serves a vital role in numerous neurological disorders. Our previous study indicated that SQ29548, an antagonist of TXA2R, attenuated the induced neuron damage in cerebral infarction animals; however, the underlying mechanism remains unknown. Certain studies revealed a new role of TXA2R in the regulation of oxidative stress, which is one of the basic pathological processes in neurological disorders. Thus, the present study attempted to examine whether the inhibition of TXA2R with SQ29548 helped to protect the nerve cells against oxidative stress. SQ29548 was utilized as a TXA2R antagonist, and relevant assays were performed to detect the cell viability, cellular reactive oxygen species (ROS) level, cell apoptosis, expression levels of superoxide dismutase­2 (SOD2), catalase and caspases, and activation of mitogen­activated protein kinase (MAPK) pathways. It was observed that hydrogen peroxide (H2O2) dose­dependently reduced the viability of SH­SY5Y cells. In addition, H2O2 raised the level of ROS in cells, inhibited the expression levels of SOD2 and catalase, and potentially enhanced cell apoptosis and the expression of caspases via activating the MAPK pathways. Pretreatment with SQ29548 not only rescued the viability of SH­SY5Y cells, but also ameliorated the intracellular ROS level and the expression levels of SOD2 and catalase. Furthermore, it decreased the cell apoptosis and the expression of caspases, possibly via the inhibition of MAPK pathways. In conclusion, SQ29548, an antagonist of TXA2R, improved the antioxidant capacities of SH­SY5Y cells and reduced the cell apoptosis through the inhibition of MAPK pathways.

Thromboxane A2 receptor antagonist SQ29548 suppresses the LPS­induced release of inflammatory cytokines in BV2 microglia cells via suppressing MAPK and NF­κB signaling pathways.

Inflammation in the brain, characterized by the activation of microglia, is hypothesized to participate in the pathogenesis of neuronal disorders. It is proposed that thromboxane A2 receptor (TXA2R) activation is involved in thrombosis/hemostasis and inflammation responses. In the present study, the anti­inflammatory effects of SQ29548 on lipopolysaccharide (LPS)­stimulated BV2 microglial cells and its molecular mechanisms were investigated. In the BV2 cell line, LPS­stimulated nitric oxide (NO) and inflammatory cytokine release, and the phosphorylation of mitogen­activated protein kinases (MAPKs) and the nuclear factor (NF)­κB were assessed using an NO assay kit, reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. In vitro studies demonstrated that SQ29548 inhibited LPS­stimulated BV2 activation and reduced the mRNA expression levels of interleukin (IL)­1ß, IL­6, tumor necrosis factor­α and inducible NO synthase via inhibition of MAPKs and the NF­κB signaling pathway. SQ29548 inhibited the LPS­induced inflammatory response by blocking MAPKs and NF­κB activation in BV2 microglial cells.

Relevance Study on Cerebral Infarction and Resistin Gene Polymorphism in Chinese Han Population.

Recent research on genome-wide associations has implicated that the serum resistin level and its gene polymorphism are associated with cerebral infarction (CI) morbidity and prognosis, and could thereby regulate CI. This study aimed to investigate the association between the resistin single nucleotide polymorphism (SNP) and the susceptibility to CI in the Chinese Han population. A total of 550 CI patients and 313 healthy controls were genotyped. Nine SNPs of the resistin gene previously shown were sequenced and assessed for an association with CI. The numbers of GG genotype carriers of rs3219175 and rs3486119 in the CI group were significantly higher than those in the control group among the middle-aged group (aged 45-65), at 76% vs 67.9% (P=0.025) and 75.5% vs 67.9% (P=0.031). rs3219175 and rs34861192 were associated with CI in the dominant and superdominant models according to the genetic model analysis (P<0.05). Meanwhile, there was strong linkage disequilibrium among the rs34124816, rs3219175, rs34861192, rs1862513, rs3745367, 180C/G and rs3745369 sites. In a haplotype analysis, the occurrence rate of the haplotype AGGCAGC was 1.97 times (P<0.05) higher in the patient group than in the control group. In addition, the numbers of GG genotype carriers of rs3219175 and rs3486119 in the middle-aged male CI patients and the middle-aged small artery occlusion (SAO) CI patients were higher than those in the control group (P<0.05). In the Chinese Han middle-aged population, the GG gene type carriers of the resistin gene sites rs3219175 and rs34861192 had a high risk for CI onset, especially in middle-aged male patients and SAO CI in all middle-aged patients.

Aspirin resistance and other aspirin-related concerns.

Aspirin is a widely used medication and has become a cornerstone for treating cardiovascular disease. Aspirin can significantly reduce the incidence of cardiovascular ischemic events, recurrence and mortality, thereby improving the long-term prognosis of patients. However, there has been a staggering increase in the volume of literature addressing the issue of so-called "aspirin resistance" in recent years, and for some patients, it is difficult to avoid adverse reactions to aspirin. In this review, we present both the historical aspects of aspirin use and contemporary developments in its clinical use.