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While cytotoxic chemotherapy remains the hallmark of cancer treatment, intensive regimens fall short in many malignancies, including high-risk neuroblastoma. One alternative strategy is to therapeutically promote tumor differentiation. We created a gene expression signature to measure neuroblast maturation, adapted it to a high-throughput platform, and screened a diversity oriented synthesis-generated small-molecule library for differentiation inducers. We identified BRD8430, containing a nine-membered lactam, an ortho-amino anilide functionality, and three chiral centers, as a selective class I histone deacetylase (HDAC) inhibitor (HDAC1 > 2 > 3). Further investigation demonstrated that selective HDAC1/HDAC2 inhibition using compounds or RNA interference induced differentiation and decreased viability in neuroblastoma cell lines. Combined treatment with 13-cis retinoic acid augmented these effects and enhanced activation of retinoic acid signaling. Therefore, by applying a chemical genomic screening approach, we identified selective HDAC1/HDAC2 inhibition as a strategy to induce neuroblastoma differentiation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.

To decrease the cost of bioethanol production, biomass recalcitrance needs to be overcome so that the conversion of biomass to bioethanol becomes more efficient. CO(2) laser irradiation can disrupt the lignocellulosic physical structure and reduce the average size of fiber. Analyses with Fourier transform infrared spectroscopy, specific surface area, and the microstructure of corn stover were used to elucidate the enhancement mechanism of the pretreatment process by CO(2) laser irradiation. The present work demonstrated that the CO(2) laser had potential to enhance the bioconversion efficiency of lignocellulosic waste to renewable bioethanol. The saccharification rate of the CO(2) laser pretreatment was significantly higher than ultrasonic pretreatment, and reached 27.75% which was 1.34-fold of that of ultrasonic pretreatment. The results showed the impact of CO(2) laser pretreatment on corn stover to be more effective than ultrasonic pretreatment.

CO2 laser pretreatment to improve the enzymatic hydrolysis of corn stover for production of monosaccharide, was investigated. Response surface methodology (RSM), at a three-variable, three-level experiment Box-Behnken design (BBD) established the following optimum pretreatment parameters: time, 67.53 min; power, 264.33 W; and liquid-to-solid ratio, 21.29:1 (mL/g). Under these conditions, the reducing sugars produced was 4.941 mg/mL for cellulase hydrolysis. This amount matched the predicted value and increased cellulase hydrolysis from 14.47% to 30.84%. Scanning electron microscopy (SEM) showed that CO2 laser pretreatment converted the smooth into a rough and porous surface, which promoted the enzyme access and resulted in a high specific reducing sugars production rate., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To observe the activities of baicalin, berberine and Astragalus polysaccharides and their combinative effects on aldose reductase (AR) by a screening model of aldose reductase inhibitor (ARI) in vitro., Methods: The inhibition of AR by baicalin, berberine and Astragalus polysaccharides and positive drug (Epalrestat) in different concentrations were evaluated, and their combinative effects were studied according to orthogonal t design., Results: Baicalin and berberine had remarkable inhibitory effects on AR, the inhibitory rates were (88.4 +/- 7.4)% and (69.0 +/- 9.4)% at the concentration of 300 microg/mL. However, the combinative effect of the inhibition on AR by the two compounds was antagonistic action. Astragalus polysaccharides had no activity of inhibition on AR., Conclusion: Baicalin and berberine are the potential AR inhibitors as they can inhibit the activity of AR in vitro.

Objective: To investigate the relationship between the polymorphism of site rs228648 in urotensin II gene and the genetic susceptibility to gestational diabetes mellitus in northern Chinese women., Methods: Genotyping was conducted to investigate the polymorphism of site rs228648 (G-A) in urotensin II gene among 70 unrelated gestational diabetes mellitus (GDM) subjects and 70 normal controls. DNA samples isolated from leucocyte of the control and study groups were analyzed for single-nucleotide polymorphisms of the urotensin II gene at positions rs228648 using polymerase chain reaction and restriction analysis., Results: (1) The distribution of genotype frequencies of site rs228648 accorded with Hardy-Weinberg's equation law, being colony representative. (2) The frequency of G allele of site rs228648 was 70.7% in GDM group, significantly higher than that in the control group (57.9%, P < 0.05); and the frequency of A allele of site rs228648 was 29.3% in GDM group, significantly lower than that in the control group (42.1%, P < 0.05). There was no significant difference in the frequency of G/G genotype between GDM group and control group (52.9% vs 41.4%, P > 0.05). (3) Women in control group were more likely to be homozygous for the allele A of site rs228648 than women with GDM. The frequency of A/A genotype of rs228648 was negatively correlated with GDM group. By the logistic procedure, after adjustment by age and gestational weeks, the odds ratio was 0.312, and Wald Confidence Limites were 0.108 to 0.900 (P = 0.031)., Conclusion: Urotensin II gene may contribute to the genetic susceptibility to gestational diabetes mellitus in northern Chinese population. G allele of site rs228648 is related to GDM possibly, and that homozygosis A of site rs228648 is likely to be an important protecting factor for GDM.

Objective: To investigate the proliferation inhibition of human leukemic cell line HL-60 and the expression of vascular endothelial growth factor (VEGF) mRNA and secretion of VEGF protein in HL-60 cells treated with diallyl disulfide (DADS)., Methods: MTT was used to test the cell growth, semi-quantitative RT-PCR and ELISA to study the expression of VEGF mRNA and secretion of VEGF protein., Results: DADS significantly inhibited proliferation of HL-60 cell and the inhibiting effects showed a dose (r > 0.9, P < 0.01) and time-dependent( r > 0.7, P < 0.01) manner. The expression of VEGF mRNA and secretion of VEGF protein could be down regulated by 0.625, 1.250, and 2.500 microg/mL DADS in HL-60 cells for 24,48 and 72 hours exposure and the effects also showed dose -dependence(r > 0.9, P < 0.01). The growth inhibition rates of DADS in HL-60 cells at three dosages for 24 hours were (8.19 +/- 3.34)%, (16.79 +/- 2.07)% and (21.30 +/- 2.72)%, those for 48 hours were (11.93 +/- 3.93)%, (22.81 +/- 2.31)% and (30.74 +/- 2.03)%, for 72 hours were (16.68 +/- 2.37)%, (28.54 +/- 3.26)% and (36.59 +/- 2.37)% respectively, The difference between the DADS-treated and untreated HL-60 cells was statistically significant (P < 0.01). There were also statistically significant differences among the three groups of different dosages (P < 0.01)., Conclusion: DADS can effectively inhibit the proliferation of HL-60 cells. DADS probably exerts its anti-leukemia effects by reducing the expression of VEGF mRNA and secretion of VEGF protein in HL-60 cells.

Objective: To investigate the influence of sea water immersion on inflammation and healing of the wounds in scalded rats., Methods: One hundred and forty-four male Wistar rats with 10% TBSA superficial partial-thickness scald were randomly divided into A (n=72, with scald) and B (n=72, with seawater immersion for 4hrs immediately after scald) groups. The serum contents of K+, Na+, Cl- were determined at 0 post-scald hour (PSH), 6PSH, 12PSH and 24 PSH with electrocyte analysis apparatus, and the changes in serum interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha) levels were determined at 0 PSH, 6PSH and 12 PSH with enzyme-linked immunosorbent assay (ELISA). The histopathological changes in the rats of the two groups were observed, and wound healing time was respectively calculated., Results: The serum contents of K+, Na+, Cl- in B group were obviously higher than those in A group. And the serum content of TNF-alpha and IL-6 in B group at 6 PSH [(140 +/- 22) ng/L, (160 +/- 41) ng/L] were significantly higher than those before scald [(29 +/- 15) ng/L, (62 +/- 17)] ng/L and in A group [(120 +/- 12) ng/L, (124 +/- 22) ng/L, ( P < 0.05)]. Compared with A group, re-epithelization of the wound differentiation in all layers of epidermis were delayed in B group, with more severe wound swelling, exudation, and topical inflammatory response. The wound healing time in B group was (16.3 +/- 1.6) d, which was obviously longer than that in A group [(14.1 +/- 1.8) d, P < 0.05)]., Conclusion: Sea water immersion combined with scald injury can aggravate the inflammatory response of the wound and delay the wound healing process.

The study was aimed to investigate the expression of VEGF mRNA and VEGF protein in HL-60 cells treated with diallyl disulfide (DADS), and to explore the antileukemic mechanism of DADS in respect of VEGF production. Semi-quantitative RT-PCR and ELISA were used to detect the expression of VEGF mRNA and secretion of VEGF protein in HL-60 cell lines treated by DADS respectively. The results showed that the expression of VEGF mRNA and secretion of VEGF protein were found in HL-60 cells. The expression of VEGF mRNA and secretion of VEGF protein in HL-60 cells could be down regulated by treatment with 0.625, 1.25, and 2.5 microg/mL DADS for 48 and 72 hours and the effects had a dose dependent relationship (r > 0.9, P < 0.01). The differences between DADS treated HL-60 cell groups and the control group were statistically significant (P < 0.01), there were also statistically significant differences among three DADS-treated HL-60 cell groups (P < 0.05). It is concluded that DADS effectively inhibits the proliferation of human leukemia cell line HL-60 cells; DADS exerts its antileukemic effects by reduction of the expression of VEGF mRNA and VEGF protein secretion.

Objective: To evaluate the feasibility and effectiveness of needle and syringe exchange program among a community of injecting drug users (IDUs) on AIDS prevention., Methods: A quasi-experiment design was used in a controlled community intervention study. Needle and syringe exchange program was implemented for 10 months in IDUs of an intervention community, including peer education and health education, provision of free needles and syringes, and collecting back of used needles and syringes by trained peer educators and local health workers, whereas no intervention measure in a control community was instituted. Interviews with IDUs were conducted before and after intervention with a snowballing strategy to evaluate its effectiveness., Results: A total of 428 and 429 IDUs were interviewed with structured questionnaire before and after intervention in intervention and control communities, respectively. Results revealed that awareness of HIV-related knowledge increased from 29.4% to 58.7% in the intervention community. Multivariate logistic regression analysis showed that awareness of HIV-related knowledge was higher in those who had read health education materials (OR = 2.93, 95% CI 2.12 - 4.04). As compared with the baseline data, frequency of sharing needles and syringes in past 30 days in the intervention community decreased from 48.9% to 20.4% in before intervention community (chi(2) = 41.02, P = 0.001), whereas there was no significant change in the control community. The causes of sharing needles and syringes in the intervention community included 'disable to get needle and syringe during the night', 'lack of needle and syringe when injecting at friend's home', 'not daring to buy needle and syringe for fear of being arrested' and 'no money to buy needle and syringe', declined markedly., Conclusions: Needle and syringe exchange program was feasible and effective in reducing their risky drug injecting behavior among IDUs in communities. Such strategy should be adopted in the country to reduce rapid spread of HIV.