Functional genetic variation in 3'UTR of PARP1 indicates a decreased risk and a better severity of ischemic stroke.

Aim of the study: Polymorphisms of DNA repair enzyme gene may alter the ability of damage repair, ischemic stroke susceptibility and outcome. This study aimed to explore the association of polymorphisms in PARP1 and the effects of interactions between genes in Chinese.Materials and methods: A total of 500 patients and 500 healthy controls were enrolled for genotyping. Results: Clinical information analysis revealed higher levels of alcohol and smoking exposure in patients with ischemic stroke, as well as chronic conditions such as diabetes, hypertension, and higher serum triglycerides concentration. In addition, Polymorphism in PARP1 rs8679 was significantly associated with the decreased ischemic stroke risk. Patients harboring the PARP1 rs8679 AG/GG genotype had a better initial stroke, and as for the mRNA level of PARP1, it was suppressed with mutant genotype in comparison with the wild genotype. Finally, the suppressed of PARP1 was induced by gain-binding ability of miR-124-5p through 3'UTR directly binding.Conclusions: In conclusion, our study demonstrates that the SNP rs8679 in PARP1 3'-UTR might act as a protective factor for the outcome of patients with ischemic stroke.

Methylene Tetrahydrofolate Reductase (MTHFR) rs868014 Polymorphism Regulated by miR-1203 Associates with Risk and Short Term Outcome of Ischemic Stroke.

BACKGROUND/AIMS: Genetic polymorphisms of methylene tetrahydrofolate reductase (MTHFR) were associated with ischemic stroke risk. This study analyzed MTHFR polymorphisms at the 3'-untranslated region for association with risk and outcome of ischemic stroke in a Chinese Han population. METHODS: 500 patients and 600 healthy volunteers were enrolled for MTHFR rs868014 genotyping identified bioinformatically. The binding of miR-1203 to MTHFR rs868014 was determined by luciferase assay, MTHFR expression was assessed using qRT-PCR, and plasma homocysteine levels were assayed by ELISA. RESULTS: Cigarette smoking, alcohol consumption, diabetes, hypertension (all P <0.001), low levels of serum high-density lipoprotein-C (P = 0.01), and high levels of serum low-density lipoprotein-C (P = 0.005) were associated with an increased risk of developing ischemic stroke. BMI and total serum cholesterol concentration was not associated with ischemic stroke. MTHFR rs868014 TC and CC genotypes were significantly associated with increased risk of ischemic stroke compared with the TT genotype (OR: 1.52; 95% CI: 1.01-3.39 for TC genotype, while OR: 1.99; 95% CI: 1.29-3.88 for CC genotype). Furthermore, the MTHFR rs868014 SNP was associated with a poor short-term ischemic stroke outcome. qRT-PCR confirmed that MTHFR rs868014 TC or CC genotypes could facilitate miR-1203 binding leading to low MTHFR levels in cells. In addition, patients carrying the MTHFR rs868014 TC or CC genotypes were associated with accumulation of serum tHcy and a poor ischemic stroke outcome. Linkage disequilibrium analysis indicated that the newly identified SNP rs868014 was strongly linked with the MTHFR A1298C polymorphism. CONCLUSION: This study demonstrates that the MTHFR rs868014 SNP is associated with increased risk in developing ischemic stroke, miR-1203 binding, low MTHFR levels in cells, and poor shot term outcome of patients.

Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma.

Targeting tumor stemness is an innovative approach to cancer treatment. Zinc Finger Protein 207 (ZNF207) is a promising target for weakening the stemness of glioma cells. Here, a series of novel N-(anthracen-9-ylmethyl) benzamide derivatives against ZNF207 were rationally designed and synthesized. The inhibitory activity was evaluated, and their structure-activity relationships were summarized. Among them, C16 exhibited the most potent inhibitory activity, as evidenced by its IC50 values ranging from 0.5-2.5 µM for inhibiting sphere formation and 0.5-15 µM for cytotoxicity. Furthermore, we found that C16 could hinder tumorigenesis and migration and promote apoptosis in vitro. These effects were attributed to the downregulation of stem-related genes. The in vivo evaluation demonstrated that C16 exhibited efficient permeability across the blood-brain barrier and potent efficacy in both subcutaneous and orthotopic glioma tumor models. Hence, C16 may serve as a potential lead compound targeting ZNF207 and has promising therapeutic potential for glioma.

Poly (Adenosine Diphosphate Ribose) Polymerase-1 Single Nucleotide Polymorphism in the 3'-Untranslated Region for Ischemic Stroke Risk Reduction.

OBJECTIVE: To determine the effect of PARP1 polymorphism on gene interactions. METHODS: A total of 500 patients and 500 healthy controls were enrolled. RESULTS: Analysis of clinical data showed that patients with stroke, diabetes, hypertension, and elevated serum triglyceride levels had higher levels of alcohol and smoking. The polymorphism of PARP1rs8679 was inversely associated with the risk of ischemic stroke. Patients with PARP1rs8679AG/ GG genotypes had a lower incidence of an initial stroke. Compared with the wild genotype, mRNA levels of PARP1 were reduced. MiR-124-5p directly induced PARP1 inhibition through the gain binding ability of 3 'UTR binding. CONCLUSION: Single nucleotide polymorphism (SNP) rs8679 in PARP13'UTR can prevent ischemic stroke.

NOX4 rs11018628 polymorphism associates with a decreased risk and better short-term recovery of ischemic stroke.

Single-nucleotide polymorphisms (SNPs) play an important role in our susceptibility to disease, the severity of illness and the way our body responds to treatment. This study evaluated the impact of three polymorphisms on the susceptibility and functional outcome of ischemic stroke (IS). Three hundred and eight patients and 300 healthy volunteers were enrolled. Polymorphisms of NOX4 rs11018628, MTHFR rs1801133 and NEIL3 rs12645561 were detected in both groups. Smoking (P<0.001), drinking (P<0.001), hypertension (P<0.001) and diabetes (P=0.006), as traditional vascular risk factors for IS, were confirmed in our study. Logistic regression analyses with adjustment for age, sex, smoking, drinking, diabetes, hypertension and total cholesterol showed that the variant genotypes of NOX4 rs11018628 were associated with a significantly decreased risk (Dominant model: OR=0.32, 95% CI=0.22-0.48, P<0.001) and a better short-term recovery of IS (Dominant model: OR=0.57, 95% CI=0.35-0.95, P=0.029). This study demonstrates that the NOX4 rs11018628 SNP is associated with decreased risk in developing IS and better short-term recovery of patients. This suggests that the genetic variant of NOX4 rs11018628 may contribute to the etiology of IS.