Molecular docking based screening of triterpenoids as potential G-quadruplex stabilizing ligands with anti-cancer activity.

Triterpenoids isolated from Ganoderma lucidum (GLTs) exhibit a broad spectrum of anti-cancer properties, including anti-proliferative, anti-metastatic and anti-angiogenic activities. Current research studies revealed the role by GLTs in inducing apoptosis and suppression of telomerase activity of cancer cells with much lower toxicity to healthy cells. Compounds selectively binding and stabilizing G-quadruplex structures could inhibit the telomerase or downregulate the oncogenes and may act as anti-cancer agents. Targeting human telomeric G-quadruplex DNA could be one of the mechanisms by which these GLTs exert anti-cancer activity. In this study, 208 GLTs were screened for ligands with high binding affinity and selectively to stabilize the pG4DNA by using the docking tool AutoDock4. The results showed that ganoderic acid A and ganoderic acid Df exhibit high binding affinity and selectively bind to the lateral groove of pG4DNA. Based on our findings, we suggest that the triterpenoid represents a new class of G-quadruplex groove binding ligands and thus act as potential anti-cancer agents.

Association between butyrylcholinesterase K variant and mild cognitive impairment in the Thai community-dwelling patients.

OBJECTIVE: To study the association of the butyrylcholinesterase K variant (BChE-K) and the plasma BChE activity with mild cognitive impairment (MCI) in Thai community-dwelling patients. METHODS: One hundred patients diagnosed with MCI and 100 control subjects were recruited from the community-dwelling setting in Bangkok, Thailand. The genotype and allele distributions of the BChE-K were determined by polymerase chain reaction and subsequent DNA sequencing. The BChE activity was measured in plasma according to the Ellman's method. RESULTS: The BChE-K allele frequencies in the Thai community-dwelling patients were in accordance with other ethnics. The BChE-K allele frequency in the control subjects (12%) was higher than that of MCI patients (5.5%), suggesting a protective role of BChE-K for MCI in the Thai community-dwelling patients. The BChE-K homozygotes were significantly associated with lower BChE activity. CONCLUSION: Our results suggested that the BChE-K may be implicated as a protective factor for MCI in the Thai community-dwelling patients, although a further study with a large sample size is warranted to confirm this.

Genetic polymorphisms and haplotypes of DNA repair genes in childhood acute lymphoblastic leukemia.

BACKGROUND: Polymorphisms of DNA repair genes can alter protein structure and may impair DNA repair capacity. Defects in repairing damaged DNA lead to genetic instability and carcinogenesis. This study was performed to evaluate the effect of the polymorphisms of DNA repair genes on risk of childhood acute lymphoblastic leukemia (ALL). PROCEDURES: We genotyped polymorphisms of X-ray repair cross-complimenting group 1 (XRCC1) codon 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln), and xeroderma pigmentosum group D (XPD) codon 312 (Asp to Asn) and 715 (Lys to Gln) in 108 children with ALL and 317 healthy controls using PCR-RFLP method. The allele, genotype, and haplotype frequencies of these polymorphisms were compared between cases and controls using Chi-square or Fisher's exact test. PHASE computer software was used to analyze estimated haplotypes of the XRCC1 and XPD polymorphisms. RESULTS: The frequency of XRCC1 194Trp allele in patients was significantly lower than that in controls (odds ratio (OR) 0.67; 95% confidence interval (CI), 0.47-0.97). Individuals with XRCC1 194 Trp/Trp genotype had a significantly reduced risk of ALL (OR 0.22; 95% CI, 0.05-0.96). The frequency of the XRCC1 haplotype B (194Trp-280Arg-399Arg) was significantly lower in children with ALL when compared to controls. The XRCC1 399Gln allele was associated with a significantly increased risk of ALL (OR 1.67; 95% CI, 1.20-2.33). The frequency of the XRCC1 haplotype C (194Arg-280Arg-399Gln) was significantly higher in patients. There was no difference of allele frequencies of the XRCC1 280 (Arg to His), XPD 312 (Asp to Asn), or XPD 715 (Lys to Gln) between cases and controls. CONCLUSION: The XRCC1 194Trp allele and haplotype B showed a protective effect against development of childhood ALL. In contrast, individuals with the XRCC1 399Gln allele and haplotype C were associated with increased risk for this disease.

The "intermediate syndrome" as critical sequelae of organophosphate poisoning: the first report of two cases in Thailand.

The authors report 2 cases of organophosphate poisoning which developed intermediate syndrome. The first case was a man who took an organophosphate insecticide, monocrotophos, and developed severe organophosphate poisoning. Respiratory support was needed. He was treated with atropine and 2-PAM. Weakness of neck muscles, proximal limb and respiratory muscle developed in the 3rd day after ingestion. By supportive treatment and careful monitoring, however, he recovered after 11 days of the poisoning. The second case was a lady who took dicrotophos. She developed severe organophosphate poisoning for which respiratory support was also needed High dose of atropine, but without 2-PAM, was administered. She developed bulbar palsy, proximal muscle and respiratory weakness 3 day after the ingestion. Ventilation support was needed for 13 days before weaning was successful. This report did not support an efficacy of pralidoxime (2-PAM) in alleviation of the intermediate syndrome, but aims to alert physicians to recognize the intermediate syndrome for which adequate respiratory care is the crucial key for its management.