Association between P2Y1 and P2Y12 polymorphisms and acute myocardial infarction and ADP-induced platelet aggregation.

BACKGROUND: The objective of this study was to investigate the relationship between P2Y1 and P2Y12 genotypes and the risk of acute myocardial infarction (AMI) in the Quanzhou population and to determine associations between P2Y1 and P2Y12 genotypes and ADP-induced platelet aggregation in this population. METHODS: All subjects were screened for P2Y1 (c.1622A > G) and P2Y12 (H1/H2, c.34C > T) polymorphisms by direct DNA sequencing. The maximal platelet aggregation rate (MAR) in AMI patients (n = 61) and healthy control subjects (n = 50) was measured by a PL-12 platelet function analyzer, and adenosine diphosphate (ADP) (5 µmol/L) was used as an agonist. RESULTS: The haploid H2 allele in the P2Y12 gene was more frequent in patients with AMI than in control subjects (OR 1.887, P = 0.005). The P2Y12 H2 haplotype was significantly associated with AMI in the codominant (P = 0.008), dominant (OR 2.103, P = 0.003), and overdominant models (OR 2.133, P = 0.003). After adjusting for potential confounders, H2 haplotype carriers had a 2.132-fold increased risk for AMI (OR 2.132, P = 0.012) compared with noncarriers. Moreover, we observed that the ADP-induced MAR in the carriers of the H2 haplotype from the control group was somewhat higher than that in noncarriers of this group (P = 0.020). However, we failed to demonstrate that the P2Y1 H1/H2 polymorphism affected ADP-induced MAR in AMI patients. Additionally, P2Y1 c.1622A > and P2Y12 c.34C > T polymorphisms were not associated with the risk of AMI or ADP-induced MAR in either group. CONCLUSIONS: Therefore, our results suggest that the P2Y12 H2 haplotype was associated with a higher risk of AMI, while its effect on increased ADP-induced platelet aggregation remains to be investigated. Thus, the P2Y12 H2 haplotype may be a potential marker for AMI.

Cyr61 decreases Cytarabine chemosensitivity in acute lymphoblastic leukemia cells via NF-κB pathway activation.

Elevated Cyr61 levels have been reported in various malignancies. Elevation of Cyr61 protein levels contributes to the proliferation, metastasis, and chemotherapy resistance of malignant cells. Previously, it was discovered that Cyr61 is elevated in both the plasma and the bone marrow supernatants of patients with acute lymphoblastic leukemia (ALL), promoting ALL cell survival. However, the role of Cyr61 in the chemotherapeutic resistance of ALL cells remains unknown. The aim of the current study was to investigate the role of Cyr61 in regulating ALL cell chemosensitivity to Ara­C. It was found that Cyr61 is overexpressed in bone marrow mononuclear cells from patients with ALL. Increased Cyr61 effectively decreased Ara­C­induced apoptosis of ALL cells, and its function was blocked by the use of the anti­Cyr61 monoclonal antibody 093G9. Furthermore, Cyr61 increased the level of Bcl­2 in Ara­C­treated ALL cells. Mechanistically, it was shown that Cyr61 affected ALL cell resistance to Ara­C partially via the NF­κB pathway. Taken together, the present study is the first, to the best of our knowledge, to reveal that Cyr61 is involved in ALL cell resistance through the NF­κB pathway. The findings support a functional role for Cyr61 in promoting chemotherapy resistance, suggesting that targeting Cyr61 directly or its relevant effector pathways may improve the clinical responses of patients with ALL.

Epidemiology of Humanpapilloma virus infection among women in Fujian, China.

BACKGROUND: Human papillomavirus (HPV) infection is the main etiological factor for the development of cervical cancer. Here we assessed the prevalence and distribution of HPV genotypes in Fujian population. METHODS: A total of 8678 women aging from 17 to 84 years olds were recruited from the Fujian Medical University Union Hospital in Fujian Province. Every woman had a face-to-face interview. Cervical samples were collected from each participant and HPV screening was conducted using microarray hybridization. RESULTS: Our study showed that the HPV prevalence in Fujian province was 38.3%. Among the positive individuals, 70.6% were detected for single HPV infection, 29.4% for multiple HPV infections. Further analysis showed that the prevalence of HPV infection significantly increased from 2009 to 2015. The four most common high risk human papillomavirus (HR-HPV) genotypes were HPV16 (8.5%), HPV52 (7.9%), HPV58 (6.2%), HPV 53 (3.5%), collectively accounting for 60.5% of all detected HPV infection. Age subgroup analysis showed two peaks for the frequencies of overall and multiple HPV infections, one for the group of women under 25 years old, and the other for the group over 55 years old. CONCLUSIONS: HPV infection is becoming serious in Fujian province, which indicates the imperative to implement a HPV vaccination and screening program for this region.

Cyr61 participates in the pathogenesis of acute lymphoblastic leukemia by enhancing cellular survival via the AKT/NF-κB signaling pathway.

Cyr61 (CCN1) is the product of a growth factor-inducible immediate early gene and is involved in cell adhesion, survival, proliferation, and differentiation. Cyr61 is overexpressed in human tumors and is involved in the development of tumors. However, the role that Cyr61 plays in acute lymphoblastic leukemia (ALL) cells remains undetermined. The aim of this study was to identify the role of Cyr61 in regulating ALL cell survival. Here, we found that the level of Cyr61 was increased in the plasma and bone marrow (BM) from ALL patients compared with samples from normal control patients. Furthermore, we observed that Cyr61 could effectively stimulate Jurkat (T ALL cell lines), Nalm-6 (B ALL cell lines), and primary ALL cell survival. Mechanistically, we showed that Cyr61 stimulated ALL cell survival via the AKT/NF-κB signaling pathways and the consequent up-regulation of Bcl-2. Taken together, our study is the first to reveal that Cyr61 is elevated in ALL and promotes cell survival through the AKT/NF-κB pathway by up-regulating Bcl-2. Our findings suggest that Cyr61 plays an important role in the pathogenesis of ALL.