Differential effects of paraoxonase 1 (PON1) polymorphisms on cancer risk: evidence from 25 published studies.

Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stress, which is thought to contribute to cancer development. PON1 activity varies widely among individuals, which is in part related to two common nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M). The polymorphisms in PON1 have been implicated in cancer risk. However, results from the studies to date have been conflicting. To clarify the association, a meta-analysis was performed for 7,073 cases and 9,520 controls from 25 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Significant associations between PON1-L55M but not Q192R polymorphism and total cancer were observed from all the comparisons. In stratified analyses, PON1-55M allele was a risk factor for breast cancer. Similarly, increased risk was observed for prostate cancer (OR = 1.18, 95% CI: 1.01-1.36, P (heterogeneity) = 0.260) and Caucasian population (OR = 1.18, 95% CI: 1.02-1.38, P (heterogeneity) = 0.1) of the LM genotype, compared with the LL genotype. For PON1-Q192R polymorphism, PON1-192R allele was a decreased risk factor for cancer in the Asian group (RR vs QQ: OR = 0.61, 95% CI: 0.38-0.98, P (heterogeneity) = 0.268; QR vs QQ: OR = 0.71, 95% CI: 0.52-0.96, P (heterogeneity) = 0.130; RR + QR vs QQ: OR = 0.71, 95% CI: 0.53-0.95, P (heterogeneity) = 0.135). Although some modest bias could not be eliminated, this meta-analysis suggests that the PON1-55M allele is a risk factor for the development of cancer, in particular for breast cancer. Future studies with larger sample sizes are warranted to further evaluate these associations.

Screening of Inherited Metabolic Disorders in Infants with Infantile Spasms.

The objective of this study is to explore the incidence of inherited metabolic disorders (IMD) in infants with infantile spasms (IS), with an attempt to improve the early diagnosis and etiological and symptomatic treatment. Urine and blood samples were collected from 60 IS patients and analyzed for the quantification of amino acids, organic acids, and fatty acids by gas chromatography-mass spectrometry and tandem mass spectrum. Routine urine tests, hepatic function tests, blood biochemistry, brain imaging, as well as examinations of the brain stem auditory/visual evoked potentials were also examined. In addition to antiepileptic therapy, etiological and symptomatic treatments were also conducted in infants with confirmed IMD and the follow-up lasted for 6 months in these pediatric patients. Metabolic disorders were found in 28 (46.67 %) of 60 IS infants, among them 13 (21.67 %) were confirmed to be with IMD. Twelve of these 13 IS patients with definite IMD diagnoses (92.31 %) experienced varying degrees of delayed development of intelligence and motor function, 8 patients (61.54 %) had abnormal cranial CT or MRI findings, 11 patients (84.61 %) had abnormal brain stem evoked potentials, 4 patients (30.77 %) had abnormal hepatic functions, 3 patients (23.07 %) had abnormal blood biochemistry, 2 patients (15.38 %) had positive (+ to ++) results for routine urine ketones, and 2 patients (15.38 %) had skin lesions. After treatment in children who were diagnosed IMD, the well controlled epileptic seizures and the satisfactory developments in mental and motor were found in 4 cases of methylmalonic acidemia, 2 cases of classical phenylketonuria, and one case of biotin deficiency disease, glutaric acidemia type I, and 4-hydroxybutyric aciduria in each. IMD is a key biological cause in IS. Early screening for IMD is warranted in IS infants to facilitate the improvement for the prognosis and an early etiological treatment.

Ratios of CD64 expressed on neutrophils, monocytes, and lymphocytes may be a novel method for diagnosis of neonatal sepsis.

INTRODUCTION: Neutrophil CD64 expression has been demonstrated as an improved diagnostic marker of infection and sepsis. The purpose of this study was to develop a new method to evaluate neutrophil CD64 expression for diagnosis of neonatal sepsis. METHODOLOGY: Eighty neonates with neonatal sepsis (21 culture positive, 59 negative) were enrolled in this prospective study along with 19 neonates with no symptoms or signs of infection as controls. Expressions of CD64 on monocytes, lymphocytes, and neutrophils were evaluated with flow cytometry (FCM). Ratios were calculated with these levels of CD64 expression. Blood culture and other laboratory exams were done at the same time for the diagnosis of neonatal sepsis. Results were compared between the neonatal sepsis and control groups. RESULTS: CD64 ratios showed significant difference between the groups (p < 0.01). Receiver operating curve (ROC) analysis showed that the CD64 ratios possessed high sensitivity (90%) and specificity (89.5%) in neonatal sepsis identification. CONCLUSIONS: The novel CD64 evaluation method, CD64 ratio, can be used as a supplementary method for diagnosis of neonatal sepsis.

Methionine synthase reductase A66G polymorphism and leukemia risk: evidence from published studies.

Methionine synthase reductase (MTRR) is required for the reductive methylation of cobalamin, which is the functional cofactorial form of methionine synthase (MS) in the remethylation of homocysteine to methionine. The MTRR A66G (rs1801394) polymorphism is found to be associated with decreased enzyme affinity for MTR, the gene that encodes MS, and has been widely investigated for cancer risk, including leukemia. However, the conclusions of epidemiological studies have always been contradictory. To further clarify the association of MTRR A66G polymorphism with the risk of leukemia, this meta-analysis was performed for 2913 cases and 4764 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Pooled ORs were determined for the co-dominant model (GG vs. AA, AG vs. AA), dominant model (GG + AG vs. AA) and recessive model (GG vs. AA+ AG), respectively. No significant associations were found for all comparisons in the overall pooled analysis. However, the results of stratified analyses revealed that MTRR A66G GG genotype was associated with decreased leukemia risk in the Caucasian population, in children and for acute lymphoblastic leukemia (ALL). In contrast, increased risk was observed in the Asian population and for acute myeloid leukemia (AML). This meta-analysis suggests that MTRR A66G GG is associated with decreased risk of leukemia in a Caucasian population and in children, especially for ALL.

[Construction of lentiviral vector for mouse CXC chemokine receptor 4 gene and its expression in eukaryotic cells].

This study was aimed to clone the gene coding mouse CXC chemokine receptor 4 (CXCR4), to construct the recombinant lentiviral vector carrying enhanced green fluorescence protein (EGFP) and to explore its expression in eukaryotic cells (293FT cells). The full length CXCR4 gene was cloned by RT-PCR using bone marrow cells from C57BL/6 mouse as template and inserted into PCR-Blunt vector. CXCR4 fragment was generated by digestion with restriction endonuclease and subcloned into a lentiviral vector to generate recombinant lentiviral vector LV-IRES-EGFP-CXCR4, which was co-transfected into 293FT cells together with envelope plasmid and packaging plasmid by lipofectamine 2000. Viruses were gathered and concentrated using ultracentrifuge, and then transfected into 293FT cells. Expression of EGFP was detected by fluorescent microscopy and flow cytometry (FCM). And the expression of CXCR4 protein was detected by Western blot. The results demonstrated that mouse CXCR4 gene was cloned and the lentiviral vector was successfully constructed. The lentiviral particles were correctly packaged, and the virus titers were above 10(8) TU/ml in the supernatant after concentration. Expression of EGFP was detected by fluorescent microscopy in the transfected 293FT cells, and the transfection efficacy > 95% was determined by FCM. Expression of CXCR4 protein detected by FCM and Western blot was significantly higher than that in control group. It is concluded that the CXCR4 gene along with the gene coding EGFP is successfully inserted into a lentiviral vector to construct a recombinant lentiviral vector, which can be expressed in eukaryotic cells.