Enhancing the accumulation of lipid and docosahexaenoic acid in Schizochytrium sp. by co-overexpression of phosphopantetheinyl transferase and ω-3 fatty acid desaturase.

Docosahexaenoic acid (DHA) as one of ω-3 polyunsaturated fatty acids (PUFAs), plays a key role in brain development, and is widely used in food additives and the pharmaceutical industry. Schizochytrium sp. is often considered as a satisfactory strain for DHA industrialization. The aim of this study was to assess the feasibility of phosphopantetheinyl transferase (PPTase) and ω-3 fatty acid desaturase (FAD) for regulating DHA content in Schizochytrium sp. PPTase is essential to activate the polyketide-like synthase (PKS) pathway, which can transfer apo-acyl-carrier protein (apo-ACP) into holo-ACP, and plays a key role in DHA synthesis. Moreover, DHA and docosapentaenoic acid (DPA) are synthesized by the PKS pathway simultaneously, so high DPA synthesis limits the increase of DHA content. In addition, the detailed mechanisms of PKS pathway have not been fully elucidated, so it is difficult to improve DHA content by modifying PKS. However, ω-3 FAD can convert DPA into DHA, and it is the most direct and effective way to increase DHA content and reduce DPA content. Based on this, PPTase was overexpressed to enhance the synthesis of DHA by the PKS pathway, overexpressed ω-3 FAD to convert the co-product of the PKS pathway into DHA, and co-overexpressed PPTase and ω-3 FAD. With these strategies, compared with wild type, the final lipid, and DHA titer were 92.5 and 51.5 g L-1 , which increased by 46.4% and 78.1%, respectively. This study established an efficient DHA production strain, and provided some feasible strategies for industrial DHA production in Schizochytrium sp.

Biosynthesis and evaluation of a novel highly water-soluble quercetin glycoside derivative.

Quercetin (1) was converted into quercetin 7-O-succinyl glucoside (2) by used Bacillus amyloliquefaciens FJ18 as a solvent-resistant whole-cell biocatalyst. The structure of the new compound was confirmed by LC-MS analysis and NMR spectroscopy. The water-solubility of this novel quercetin 7-O-succinyl glucoside (2) was approximately 1000 times higher than that of native quercetin (2). Quercetin (1) and quercetin 7-O-succinyl glucoside (2) exhibited significant DPPH scavenging capacity with IC50 values of 23.55 and 36.05 µM, respectively. Both compounds showed moderate cytotoxic effects against the two human cancer cell lines (MCF-7 and HepG2) with IC50 values ranging from 39.45-63.38 µM.

SPINK1 Gene is Significantly Associated With Pancreatitis: A Comprehensive Meta-Analysis.

OBJECTIVES: This research was applied to case-control studies of the association between pancreatitis and SPINK1 gene to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. METHODS: MEDLINE and Embase were searched to identify longitudinal studies evaluating pancreatitis and SPINK1. Odds ratios (ORs) and 95% confidence interval (CI) were pooled using random-effect models and calculated using Carlin method. Publication bias was assessed using Egger et al's approach (A famous statistic method by Egger et al). Sensitivity, heterogeneity, and trim and fill analyses were conducted. RESULTS: Based on the results, we found that (1) the results support for the association between pancreatitis and SPINK1, when analyzed totally and by subdivision (total [OR, 7.771; 95% CI, 5.232-11.543; P < 0.000]; European [OR,6.400; 95% CI, 4.346-9.426; P < 0.000]; Asian [OR, 11.823; 95% CI, 4.612-30.310; P < 0.000]; American [OR, 3.777; 95% CI, 1.596-8.939; P = 0.002]; mixed: [OR, 13.566; 95% CI, 2.322-79.252, P = 0.004]); (2) no evidence indicates that this association is accounted for by any one study, and no evidence indicates any publication bias exists. CONCLUSIONS: The results indicated that SPINK1 gene, particularly the N34S mutation, has a genetic association with the development of pancreatitis.

Quantitative assessment of the association between rs2046210 at 6q25.1 and breast cancer risk.

Genome-wide association studies (GWAS) have identified several genetic susceptibility loci for breast cancer (BC). One of them, conducted among Chinese women, found an association of rs2046210 at 6q25.1 with the risk of BC recently. Since then, numerous association studies have been carried out to investigate the relationship between this polymorphism and BC risk in various populations. However, these have yielded contradictory results. We therefore performed a meta-analysis to clarify this inconsistency. Overall, a total of 235003 subjects based on 13 studies were included in our study. Significantly increased BC risk was detected in the pooled analysis [allele contrast: OR = 1.13, 95%CI = 1.10-1.17, P(Z) <10(-5), P(Q) <10(-4); dominant model: OR = 1.21, 95%CI = 1.14-1.27, P(Z) <10(-5), P(Q) <10(-4); recessive model: OR = 1.18, 95%CI = 1.12-1.24, P(Z) <10(-5), P(Q) = 0.04]. In addition, our data revealed that rs2046210 conferred greater risk in estrogen receptor (ER)-negative tumors [OR = 1.27, 95%CI = 1.15-1.40, P(Z) <10(-5), P(Q) <10(-4)] than in ER-positive ones [OR = 1.18, 95%CI = 1.09-1.28, P(Z) <10(-4), P(Q) = 0.0003]. When stratified by ethnicity, significant associations were found in Caucasian and Asian populations, but not detected among Africans. There was evidence of heterogeneity (P<0.05), however, the heterogeneity largely disappeared after stratification by ethnicity. The present meta-analysis demonstrated that the rs2046210 polymorphism may be associated with increased BC susceptibility, but this association varies in different ethnicities.

HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese.

AIM: Allopurinol is widely used as an effective urate-lowering drug and is one of the most frequent causes of cutaneous adverse drug reactions (cADRs). Recently, a strong association of HLA-B*58:01 with allopurinol-induced severe cADRs was identified. This study investigated the predisposition to different types of allopurinol-cADRs conferred by HLA-B*5801 in a Han population from mainland China. PATIENTS & METHODS: HLA-B genotyping was performed on 38 Chinese patients with different types of allopurinol-cADRs from 2008 to 2011. RESULTS: All the allopurinol-cADR patients carried HLA-B*58:01, in contrast with only 11.11% (7/63) in the allopurinol-tolerant patients (odds ratio [OR] = 580.07; p < 0.0001) and 13.99% (80/572) in a Han Chinese population from the human MHC database (dbMHC; OR: 471.09; p < 0.0001) carried the genotype. Each type of allopurinol cADRs revealed a statistically significant association with HLA-B*58:01. In particular, the risk of allopurinol-induced maculopapular eruption was significantly higher in patients with HLA-B*58:01 (OR: 339.00; p < 0.0001). CONCLUSION: The strong association of both the mild and severe types of allopurinol cADRs with the HLA-B*58:01 allele were observed. The results indicated that the prospective use of a genetic test of HLA-B*58:01 might reduce the prevalence of allopurinol-induced cADRs. Original submitted 7 March 2012; Revision submitted 21 May 2012.

Quantitative assessment of the effect of LRRK2 exonic variants on the risk of Parkinson's disease: a meta-analysis.

Leucine-rich repeat kinase 2 (LRRK2, PARK8) gene has attracted considerable attention since the variants in this gene are recognized as the most common cause of Parkinson's disease (PD) so far. A number of association studies concerning variants of LRRK2 gene and PD susceptibility have been conducted in various populations. However, some results were inconclusive. To derive a more precise estimation of the relationship between LRRK2 and genetic risk of PD, we performed a comprehensive meta-analysis which included 27,363 cases and 29,741 controls from 61 published case-control studies. Totally, the effect of five LRRK2 variants all within the coding regions, i.e. G2019S, G2385R, R1628P, P755L and A419V, were evaluated in the meta-analysis using fixed effect model or random effects model if heterogeneity existed. There were genetic associations between four variants (G2019S, G2385R, R1628P and A419V) and increased PD risk, while there was no evidence of statistically significant association between P755L and PD. Publication bias and heterogeneity were absent in most analyses. Within its limitations, this meta-analysis demonstrated that the G2019S, G2385R, R1628P and A419V variations are risk factors associated with increased PD susceptibility. However, these associations vary in different ethnicities.

HTR2C promoter polymorphisms are associated with risperidone efficacy in Chinese female patients.

AIMS: A number of studies demonstrate that the polymorphisms in the 5 region of HTR2C play a pivotal role in antipsychotic drug efficacy. Since risperidone is an antagonist of HTR2C, polymorphic variations in HTR2C may explain variability in response to risperidone treatment. We analyzed HTR2C polymorphisms for association with efficacy of risperidone monotherapy. MATERIALS & METHODS: We genotyped five SNPs distributed throughout the HTR2C gene and examined them for association using the Brief Psychiatric Rating Scale score in 130 Chinese schizophrenic patients following an 8-week period of risperidone monotherapy. All the patients were receiving the atypical antipsychotic drug treatment for the first time and had a 4-week medication-free period before research began. RESULTS: We found rs518147, rs1023574 and rs9698290 were significantly associated with risperidone treatment in female patients (F = 4.75, degrees of freedom = 2 and p = 0.011; F = 4.329, degrees of freedom = 2 and p = 0.016; F = 4.188, degrees of freedom = 2 and p = 0.019, respectively) and they were also found to be in one linkage disequilibrium block. CONCLUSION: Our results indicate that variants in the HTR2C promoter region are likely to affect the risperidone therapeutic effect in female mainland patients. It may be helpful to investigate a combination of other clinical factors to predict atypical antipsychotic efficacy.

[Prevalence and etiology of people with hearing impairment in China].

OBJECTIVE: To investigate the prevalence and etiology of people with hearing disability in China and to provide evidence for development of related prevention and treatment strategies. METHODS: Using the statistics and inference from data of the Second China National Sample Survey on Disability. RESULTS: 27.80 million people were diagnosed with hearing disability, including 20.04 million with pure disability. The overall prevalence was 2.11% including 'single disability' as 1.52% (accounting for 72.08%) and the rate was 11.04% among the elderly(accounting for 73.57%). The prevalence of hearing disability was higher in males than in females as well as higher in the rural than in the urban. Sufferers were mainly engaging in agriculture with poor education background. Among all the people with hearing disability, Grade III and IV was accounted for 73.42% but among the elderly, they were accounted for 79.13%. Grade I and II was accounted for 67.36% among children aged four to six and 83.90% in children aged below three. Speech disabilities were more than 70% in aged below six. The whole etiology contains presbycusis, unknown causation and tympanitis with primary causes as heredity, pregnant virus infection, neonatal asphyxiation, drug-induced deafness, premature delivery and low birth avoirdupois, other than unknown deaf among the 0-6 year olds. However, the primary causation would include presbycusis, tympanitis, sickness, noise/detonation and drug-induced deafness for the elderly. CONCLUSION: Active prevention on presbycusis with emphasis on prevention and cure to rural population was important in reducing the venture of hearing disability. Related consultation on genetic factors was another measure to be taken to prevent hearing disability developed in the newborns.

[Status of demands on rehabilitation among handicapped persons of six categories in Beijing].

OBJECTIVE: To explore the status of rehabilitation demands and services of persons with disability in Beijing and to provide evidence for rehabilitation establishment programmed by government and civil society. METHODS: Using both qualitative and descriptive methodologies to analyze the data of 4852 disabled persons who had been confirmed of requiring rehabilitation services in Beijing. Data was from the Second China National Sample Survey on Disability in conferring the demands for rehabilitation services. RESULTS: The consciousness and demand for rehabilitation was higher among urban disabled residents than those living in the rural areas. Demand on rehabilitation training from children was accounted for 75.23%. Rates of demand on assistant device and medical service among the elderly were 57.05%, 66.86% respectively. Primary rehabilitation format of grade I and II appeared to be community-based and family service while grade III and IV were institutional rehabilitation programs. Rates on needs regarding vision and limb accounted for 85.23% and 59.91% respectively. 76.95% of the disability persons among intelligentsia needed community and family service. The rates on demand of medical treatment of mental, vision, limbs services were 92.80%, 86.77% and 68.24% respectively while the demand for assistant device of hearing disability was 83.09%. Rates of demand on rehabilitative training from mental, dication and mind disabled were 84.36%, 77.42%, 62.82%. Other kinds of demand and services seemed relatively low other than medical treatment. CONCLUSION: The gap between demand and salvation on rehabilitation was relatively great, suggesting the enhancement of disabled rehabilitation programs be strengthened to promote the build-up of a correct concept on rehabilitation among the disabled. Demands from the disabled persons should be extensively met.