Effects of lncRNA gm4419 on rats with hypertensive cerebral atherosclerosis through NF-κB pathway.

OBJECTIVE: To explore the effects of long non-coding ribonucleic acid (lncRNA) Gm4419 on rats with hypertensive cerebral atherosclerosis through the nuclear factor-kappa B (NF-κB) pathway. MATERIALS AND METHODS: Healthy male rats were selected and randomly divided into control group, model group (hypertensive cerebral atherosclerosis model), and lncRNA group (hypertensive cerebral atherosclerosis model + lncRNA injection). Neurological deficit scoring criteria, flow cytometry, Western blotting, and staining method were adopted to measure the differences in the neurological function score, NF-κB activity, and chemerin level of rats in the three groups. RESULTS: The neurological scores revealed that the neurological function of rats was not damaged in control group, while it was severely damaged in model group. However, the neurological function of rats was more severely damaged in lncRNA group than that in control group and model group, while the neurological function deficits were slighter in model group. In terms of NF-κB expression activity in mononuclear cells, the serum activity of NF-κB in control group appeared the lowest among the three groups and was significantly higher in lncRNA group than in model group. The serum chemerin level was evidently increased in model group compared with control group, while it was significantly decreased in lncRNA group compared with model group and control group. Moreover, the levels of NF-κB and chemerin were most evidently influenced in lncRNA group. CONCLUSIONS: Activating the NF-κB signal, lncRNA Gm4419 promotes the expression of chemerin signal, accelerates the apoptosis of nerve cells, and motivates the deterioration of hypertensive cerebral arteriosclerosis.

Methylmercury-l-Cysteine targeting L-type amino acid transporter conjugate cytotoxicity on C6 glioma cells.

Glioma is the most common primary tumor in the brain, accounting for about 40~50% of intracranial primary tumors. Most chemotherapeutic drugs have difficulty in penetrating the blood-brain barrier, and their clinical applications are greatly limited. We evaluated the effects of methylmercury-L-cysteine (MeHg-L-cys) and methylmercury chloride (MMC) on apoptosis of C6 glioma cells. L-type amino acid transporter (LAT1) was used to investigate the targeted transport function and cytotoxicity of MeHg- L-cys in glioma. MeHg-L-cys enhanced the ability of targeting glioma cells and reduced the adverse reactions to normal brain tissues. Therefore, it is significantly important to develop new anti-glioma drugs targeting the blood-brain barrier.

Genetic polymorphisms in MDR1 and CYP3A5 and MDR1 haplotype in mainland Chinese Han, Uygur and Kazakh ethnic groups.

BACKGROUND AND OBJECTIVE: The drug transporter MDR1 and the drug metabolizing enzyme CYP3A are the two major biological factors determining the pharmacokinetics of many drugs. The functional MDR1 single nucleotide polymorphisms (SNPs) and a prevalent CYP3A5 SNP show marked interethnic variation among Orientals, Caucasians and Africans. In this study, we investigated the distribution of MDR1 and CYP3A5 SNPs among mainland Chinese Han, Uygur and Kazakh ethnic groups. METHODS: Genotypes of the MDR1 C1236T, G2677T/A and C3435T, and CYP3A5*3, CYP3AP1*3 SNPs were determined in 434 unrelated healthy subjects (165 Chinese Han, 161 Chinese Uygur and 108 Chinese Kazakh) using polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS AND DISCUSSION: A significantly higher MDR1 3435T variant frequency was observed in Uygur (52.8%), than in Kazakh (39.8%) and Han (37.9%) Chinese (P < 0.01, Fisher's exact test). There was no significant difference in MDR1 1236T and 2677T/A variant frequencies between Han, Uygur and Kazakh. CYP3A5*3 (G) allele was observed at intermediate frequencies in Uygur (84.8%) and Kazakh (86.6%), relative to Han (72.7%) and values previously reported in Caucasians (91.7%). The CYP3AP1*3 (A) allele was strongly linked to CYP3A5*3 in Chinese Han, Uygur and Kazakh. CONCLUSION: Significant interethnic differences in MDR1 haplotype and CYP3A5 variant frequencies exist between mainland Chinese Han and Caucasians, and the intermediate frequencies observed in Chinese Uygur and Kazakh might be due to the genetic admixture of Eurasians and Orientals.

Expression and localisation of urokinase-type plasminogen activator gene in gliomas.

Urokinase-type plasminogen activator (uPA) activity is related to the malignant biological behaviour of tumours. In the present study, we examined the presence and distribution of uPA in human gliomas. The amounts of uPA were measured by Northern blotting hybridisation and immunohistochemistry in 43 gliomas and five normal brain specimens. Their relation to the clinical history was comprehensively analysed. All tissues expressed 2.5 kb transcripts of uPA mRNA. The uPA mRNA levels were significantly higher in high grade gliomas than they were in low grade gliomas and normal brain tissue (P < 0.01). Levels of uPA mRNA expression in tumour tissues with recurrence within 18 months postoperatively and survival less than 3 years were significantly higher than counterparts (P < 0.01). The uPA mRNA was also expressed in tumour cells near necrotic areas. The uPA protein expression was consistent with the uPA mRNA expression. The distribution of uPA protein immunoreactivity was mainly in tumour cells and microvascular endothelial cells of glioblastomas and anaplastic astrocytomas, localising in the cytoplasm, especially at sites of vascular proliferation and at the leading edges of tumours. These results suggest that expression of the uPA gene is associated with the malignant progression of gliomas and may play an important role in the recurrence and invasive behaviors of higher grade gliomas.

Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors.

BACKGROUND: The presence of simian virus 40 (SV40) in human brain tumors remains a controversial issue. Even if SV40 does exist in brain tumors, the questions of whether it is associated with brain tumorigenesis and by what mechanisms are unknown. METHODS: SV40 large tumor antigen (Tag) was investigated by immunoprecipitation, silver staining, and Western blot analysis in 65 brain tumor cases and 8 cases of normal brain tissue. Tag-p53 and Tag-pRb complexes were screened by immunoprecipitation and Western blot analysis in 18 and 15 Tag positive tumor tissues, respectively. RESULTS: Tag was found in all 8 cases of ependymoma and 2 cases of choroid plexus papilloma, 90% of pituitary adenoma cases (9 of 10), 73% of astrocytoma cases (11 of 15), 70% of meningioma cases (7 of 10), 50% of glioblastoma multiforme cases (4 of 8), and 33% of medulloblastoma cases (2 of 6). Five oligodendroglioma cases, 1 pineocytoma case, and 8 cases of normal brain tissue were negative for Tag. The Tag-p53 complex was detected in all 18 Tag positive tumors tested and the Tag-pRb complex was detected in all 15 Tag positive tumors tested. CONCLUSIONS: SV40 Tag not only is expressed in brain tumors; it also can form specific complexes with tumor suppressors p53 and pRb. SV40 is correlated with brain tumorigenesis. The inactivation of p53 and pRb due to the formation of Tag-p53 and Tag-pRb complexes possibly is a significant mechanism in the etiopathogenesis of brain tumors.