Coagulation as an effective method for cyanobacterial bloom control: A review.

Eutrophication, the over-enrichment with nutrients, for example, nitrogen and phosphorus, of ponds, reservoirs and lakes, is an urgent water quality issue. The most notorious symptom of eutrophication is a massive proliferation of cyanobacteria, which cause aquatic organism death, impair ecosystem and harm human health. The method considered to be most effective to counteract eutrophication is to reduce external nutrient inputs. However, merely controlling external nutrient load is insufficient to mitigate eutrophication. Consequently, a rapid diminishing of cyanobacterial blooms is relied on in-lake intervention, which may encompass a great variety of different approaches. Coagulation/flocculation is the most used and important water purification unit. Since cyanobacterial cells generally carry negative charges, coagulants are added to water to neutralize the negative charges on the surface of cyanobacteria, causing them to destabilize and precipitate. Most of cyanobacteria and their metabolites can be removed simultaneously. However, when cyanobacterial density is high, sticky secretions distribute outside cells because of the small size of cyanobacteria. The sticky secretions are easily to form complex colloids with coagulants, making it difficult for cyanobacteria to destabilize and resulting in unsatisfactory treatment effects of coagulation on cyanobacteria. Therefore, various coagulants and coagulation methods were developed. In this paper, the focus is on the coagulation of cyanobacteria as a promising tool to manage eutrophication. Basic principles, applications, pros and cons of chemical, physical and biological coagulation are reviewed. In addition, the application of coagulation in water treatment is discussed. It is the aim of this review article to provide a significant reference for large-scale governance of cyanobacterial blooms. PRACTITIONER POINTS: Flocculation was a promising tool for controlling cyanobacteria blooms. Basic principles of four kinds of flocculation methods were elucidated. Flocculant was important in the flocculation process.

Cultivation of algal-bacterial granular sludge and degradation characteristics of tetracycline.

Due to the increasing use of antibiotics, tetracycline was frequently detected in wastewater. As a novel technology, algal-bacterial granular sludge process is expected to be widely used in wastewater treatment. However, the degradation effect of tetracycline by algal-bacterial granular sludge process and its degradation path is still unknown. In this study, mature and stable algal-bacterial granular sludge was cultured and the degradation of tetracycline by it was investigated. The results showed that the removal amount of 1-25 mg/L tetracycline by algal-bacterial granular sludge was 0.09-1.45 mg/g volatile suspended solids (VSS), in which the adsorption amount was 0.06-0.17 mg/g VSS and the degradation amount was 0.03-1.27 mg/g VSS. Tetracycline biosorption was dominant at its concentration of 1-3 mg/L, while biodegradation was predominant at 5-25 mg/L of tetracycline. At tetracycline concentration of 3-5 mg/L, the contribution of biosorption and biodegradation to tetracycline removal by algal-bacterial granular sludge process was almost equal. Algal-bacterial granular sludge could effectively degrade tetracycline through demethylation, dehydrogenation, deacylation, and deamination or their combination. In addition, the degradation products were nontoxic and hardly pose a threat to environmental health. The research results of this paper provide a solid theoretical basis for tetracycline removal by algal-bacterial granular sludge and a reference for the development of algal-bacterial granular sludge process for wastewater treatment in the presence of tetracycline. PRACTITIONER POINTS: Mature and stable algal-bacterial granular sludge was cultured. Tetracycline was removed by algal-bacterial granular sludge through biosorption and biodegradation. Algal-bacterial granular sludge could degrade tetracycline through demethylation, dehydrogenation, deacylation, and deamination or their combination. The degradation products were nontoxic.

The distinct resistance mechanisms of cyanobacteria and green algae to sulfamethoxazole and its implications for environmental risk assessment.

Cyanobacteria and green algae are the OECD recommended test organisms for environmental toxicity assessments of chemicals. Whether the differences in these two species' responses to the identical chemical affect the assessment outcomes is a question worth investigating. Firstly, we investigated the distinct resistance mechanisms of Synechococcus sp. (cyanobacteria) and R. subcapitata (green algae) to sulfamethoxazole (SMX). The antioxidant system analysis demonstrated that R. subcapitata mainly relies on enhancing the activity of first line defense antioxidants, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), which is the most powerful and efficient response to get rid of ROS, whereas Synechococcus sp. depends upon increasing the activity of glutathione-S-transferase (GST) and GPx to resist oxidative stress. Besides, a total 7 transformation products (TPs) of SMX were identified in R. subcapitata culture medium. The analysis of conjectural transformation pathways and the predicted toxicity indicates that R. subcapitata could relieve SMX toxicity by degrading it to low eco-toxic TPs. Additionally, we summarized numerous exposure data and assessed the environmental risk of various antibiotics, revealing an inconsistent result for the same type of antibiotic by using cyanobacteria and green algae, which is most likely due to the different resistance mechanisms. In the future, modified indicators or comprehensive assessment methods should be considered to improve the rationality of environmental toxicity assessments.

Genetic diversity and fingerprinting of 33 standard flue-cured tobacco varieties for use in distinctness, uniformity, and stability testing.

BACKGROUND: At present, the distinctness, uniformity, and stability (DUS) testing of flue-cured tobacco (Nicotiana tabacum L.) depends on field morphological identification, which is problematic in that it is labor intensive, time-consuming, and susceptible to environmental impacts. In order to improve the efficiency and accuracy of tobacco DUS testing, the development of a molecular marker-based method for genetic diversity identification is urgently needed. RESULTS: In total, 91 simple sequence repeats (SSR) markers with clear and polymorphic amplification bands were obtained with polymorphism information content, Nei index, and Shannon information index values of 0.3603, 0.4040, and 0.7228, respectively. Clustering analysis showed that the 33 study varieties, which are standard varieties for flue-cured tobacco DUS testing, could all be distinguished from one another. Further analysis showed that a minimum of 25 markers were required to identify the genetic diversity of these varieties. Following the principle of two markers per linkage group, 48 pairs of SSR markers were selected. Correlation analysis showed that the genetic relationships revealed by the 48 SSR markers were consistent with those found using the 91 SSR markers. CONCLUSIONS: The genetic fingerprints of the 33 standard varieties of flue-cured tobacco were constructed using 48 SSR markers, and an SSR marker-based identification technique for new tobacco varieties was developed. This study provides a reliable technological approach for determining the novelty of new tobacco varieties and offers a solid technical basis for the accreditation and protection of new tobacco varieties.

Photodegradation of microcystin-LR by pyridyl iron porphyrin immobilized on NaY zeolite.

A novel photocatalyst, FeTPyPY, was prepared by immobilizing water-soluble tetra(4-pyridyl)phenyl iron-porphyrin (FeTPyP) on NaY zeolite to degrade microcystin-LR (MC-LR), one of the most toxic microcystins (MCs). UV-Vis analysis, UV-Vis diffuse reflectance spectroscopy, infrared spectroscopy, cyclic voltammetry and transmission electron microscopy were employed to characterize immobilized FeTPyPY. Under visible light (λ ≥ 420 nm), MC-LR was degraded utilizing immobilized FeTPyPY by activating molecular oxygen. The results showed that 85% of MC-LR was efficiently degraded by FeTPyPY with loading amount 100:1 (mNaY:mFeTPyP) after 300 min of visible light illumination. Moreover, FeTPyPY was stable in the degradation system with pH 7.0. The degradation mechanism was evaluated using electron spin resonance, and the results demonstrated that highly reactive oxygen species (•OH radical) were generated in the system to degrade MC-LR. Therefore, immobilized FeTPyPY was available to break down the toxic groups within MC-LR by utilizing environmental •OH radical under circumneutral condition.

Antiviral Effects of Novel 2-Benzoxyl-Phenylpyridine Derivatives.

Coxsackievirus B3 (CVB3) is the most common cause of acute and chronic viral myocarditis, primarily in children, while human adenovirus infections represent a significant cause of morbidity and mortality worldwide, in people of all ages. A series of novel 2-benzoxyl-phenylpyridine derivatives were evaluated for their potential antiviral activities against CVB3 and adenovirus type 7 (ADV7). Preliminary assays indicated that some of these compounds exhibited excellent antiviral effects on both CVB3 and ADV7 viruses; they could effectively inhibit virus-induced cytopathic effects, reduce viral progeny yields, and had similar or superior antiviral activities compared with the control drug, ribavirin. Further, these compounds targeted the early stages of CVB3 replication in cells, including viral RNA replication and protein synthesis, rather than inactivating the virus directly, inhibiting virus adsorption/entry, or affecting viral release from cells. Our data demonstrate that the tested 2-benzoxyl-phenylpyridine derivatives are effective inhibitors of CVB3 and ADV7, raising the possibility that these compounds might be feasible candidates for anti-viral agents.

A haplotype block associated with thousand-kernel weight on chromosome 5DS in common wheat (Triticum aestivum L.).

Spike number per unit area, number of grains per spike, and thousand-kernel weight (TKW) are important yield components for wheat (Triticum aestivum L.). TKW has the highest heritability among the three components. We validated 27 simple sequence repeat (SSR) loci associated with TKW in an F(2:5) breeding population grown in four environments. A cfd7(8265bp) marker on chromosome 5DS showed the strongest association with TKW and had a significantly positive effect on TKW compared to allele cfd7(8259bp), with mean increases of 5.17, 3.63, 4.11, and 5.16 g in the four environments. Markers cfd67 and cfd40 flanking cfd78 also showed significantly positive associations with TKW with increases of 5.11, 3.29, 4.31, and 4.50 g for cfd67(205), and 4.98, 3.49, 4.06, and 4.84 g for cfd40(187) compared with cfd67(203) and cfd40(190) in the four environments, respectively. A major quantitative trait locus for TKW spanning 2.94 cM on chromosome 5DS was detected by association mapping. Strong linkage disequilibrium (LD) (r(2) > 0.2) was detected among the three linked markers, which formed three haplotype blocks in the F(2:5) breeding population. Mean TKW differences between HapB-I and HapB-II were 5.80, 4.41, 4.02, and 5.06 g in the four environments, respectively. Moreover, significant LD was detected only between cfd78 and cfd67 and between cfd67 and cfd40 in a germplasm collection. This study provides a base for cloning genes related to TKW on chromosome 5DS.

Effects of light intensity on components and topographical structures of extracellular polysaccharides from the cyanobacteria Nostoc sp.

A study on the effects of light intensity (40 and 80 µE/m(2)/sec) on the components and topographical structures of extracellular polysaccharides (EPS) was carried out in cyanobacteria Nostoc sp.. EPS yield increased with light intensity. However, light intensity did not significantly affect the EPS fractions and monosaccharide composition. Higher light intensity generally resulted in higher protein content of EPS in similar fractions. The topographical structure of EPS, investigated by atomic force microscopy, appeared as spherical lumps, chains and networks. The long chains were observed at higher light intensity. Thus, light intensity affected the yield and nature of EPS.

The role of transforming growth factor ß1 in fractional laser resurfacing with a carbon dioxide laser.

The aim of this study was to investigate the role of transforming growth factor ß1 in mechanisms of cutaneous remodeling induced by fractional carbon dioxide laser treatment. The dorsal skin of Kunming mice was exposed to a single-pass fractional CO2 laser treatment. Biopsies were taken at 1 h and at 1, 3, 7, 14, 21, 28, and 56 days after treatment. Transforming growth factor (TGF) ß1 expression in skin samples was evaluated by ELISA, dermal thickness by hematoxylin-eosin staining, collagen and elastic fibers by Ponceau S and Victoria blue double staining, and types I and III collagens by ELISA. The level of TGF ß1 in the laser-treated areas of skin was significantly increased compared with that in the control areas on days 1 (p < 0.05), 3 (p < 0.01), and 7 (p < 0.05) and then decreased by day 14 after treatment, at which time it had returned to the baseline level. Dermal thickness and the amount of type I collagen of the skin of the laser-treated areas had increased significantly (p < 0.05) compared with that in control areas on days 28 and 56. Fibroblast proliferation showed a positive correlation with TGF ß1 expression during the early stages (r = 0.789, p < 0.01), and there was a negative correlation between the level of TGF ß1 and type I collagen in the late stages, after laser treatment (r = -0.546, p < 0.05). TGF ß1 appears to be an important factor in fractional laser resurfacing.

Photoautotrophic outdoor two-stage cultivation for oleaginous microalgae Scenedesmus obtusus XJ-15.

In this study, Scenedesmus obtusus XJ-15 was firstly selected from seven strains microalgae (Chlorophyta, Scenedesmaceae) and then cultivated using a two-stage strategy, which composed of fast cell growth in stage I and followed by lipid induction in stage II in 5-L flasks outdoors. In stage I, the biomass productivity was increased from 139.4 to 212.1 mg L(-1) d(-1). In stage II, lipid content was increased from 26.1% to 47.7% by adding NaCl into the culture. This two-stage process was also realized in an 140-L photobioreactor outdoors, with a biomass productivity of 86.5 mg L(-1) d(-1) and CO2 fixation rate of 170.0 mg L(-1) d(-1) in the first stage, and high lipid content of 42.1% in the second stage. With such a culture strategy, the overall lipid productivity was improved and better biodiesel quality was obtained. These results suggested the photoautotrophic two-stage system was not only feasible but also effective.

Feasibility of biodiesel production by microalgae Chlorella sp. (FACHB-1748) under outdoor conditions.

Chlorella sp. (FACHB-1748) was cultivated outdoors under natural sunlight to evaluate its potential for biofuel production. Urea was selected as nitrogen source, and the concentration was optimized. When the culture reached the late exponential stage, a triggering lipid accumulation test was conducted using different concentrations of sodium chloride and acetate. A scaling-up experiment was also conducted in a 70L photobioreactor. The highest biomass productivity (222.42, 154.48 mg/L/d) and lipid productivity (64.30, 33.69mg/L/d) were obtained with 0.1g/L urea in 5 and 70 L bioreactors, respectively. The highest lipid content (43.25%) and lipid yield (1243.98 mg/L) were acquired with the combination of 10 g/L sodium chloride and acetate. Moreover, the qualities of biodiesel, cetane number, saponification value, iodine value, and cold filter plugging point complied with the standards set by the National Petroleum Agency (ANP255), Standard ASTMD6751, and European Standard (EN 14214).

Evaluation of oil-producing algae as potential biodiesel feedstock.

This study attempted to connect the dots between laboratory research and the outdoors. Chlorella sp. NJ-18 was selected among seven oil-producing algae cultivated in this study because it had the highest lipid productivity. The nitrogen and phosphorus concentrations for cultivating this Chlorella strain were optimized indoors. This strain was incubated outdoors in a 70 L photobioreactor, containing the favorable nitrogen (8.32 mM urea) and phosphorus (0.18 mM monopotassium phosphate) concentrations. Semi-continuous cultivation was performed by harvesting 30 L biomass and replacing it with fresh medium. The maximum biomass and lipid productivity acquired outdoors were 91.84 and 24.05 mg L(-1) d(-1), respectively. Furthermore, biomass productivity could be maintained at a high level throughout the cultivation process when using the semi-continuous mode, whereas it decreased dramatically in batch cultures. More than 95% of the total fatty acids obtained were C16 and C18, which are the main components for biofuel.

Identifying loci influencing 1,000-kernel weight in wheat by microsatellite screening for evidence of selection during breeding.

Chinese wheat mini core collection (262 accessions) was genotyped at 531 microsatellite loci representing a mean marker density of 5.1 cM. One-thousand-kernel weights (TKW) of lines were measured in five trials (three environments in four growing seasons). Structure analysis based on 42 unlinked SSR loci indicated that the materials formed two sub-populations, viz., landraces and modern varieties. A large difference in TKW (7.08 g, P<0.001) was found between the two sub-groups. Therefore, TKW is a major yield component that was improved in the past 6 decades; it increased from a mean 31.5 g in the 1940s to 44.64 g in the 2000s, representing a 2.19 g increase in each decade. Analyses based on a mixed linear model (MLM), population structure (Q) and relative kinship (K) revealed 22 SSR loci that were significantly associated with mean TKW (MTKW) of the five trials estimated by the best linear unbiased predictor (BLUP) method. They were mainly distributed on chromosomes of homoeologous groups 1, 2, 3, 5 and 7. Six loci, cfa2234-3A, gwm156-3B, barc56-5A, gwm234-5B, wmc17-7A and cfa2257-7A individually explained more than 11.84% of the total phenotypic variation. Favored alleles for breeding at the 22 loci were inferred according to their estimated effects on MTKW based on mean difference of varieties grouped by genotypes. Statistical simulation showed that these favored alleles have additive genetic effects. Frequency changes of alleles at loci associated with TKW are much more dramatic than those at neutral loci between the sub-groups. The numbers of favored alleles in modern varieties indicate there is still considerable genetic potential for their use as markers for genome selection of TKW in wheat breeding. Alleles that can be used globally to increase TKW were inferred according to their distribution by latitude and frequency of changes between landraces and the modern varieties.

The role of vascular endothelial growth factor in fractional laser resurfacing with the carbon dioxide laser.

The aim of this study was to analyze the role of vascular endothelial growth factor (VEGF) in mechanisms of cutaneous remodeling induced by fractional CO(2) laser treatment. The dorsal skin of Kunming mice was exposed to a single-pass fractional CO(2) laser treatment. Biopsies were taken 1 h, and 1, 3, 7, 14, 28 and 56 days after treatment. Skin samples VEGF expression was evaluated by immunohistochemistry and ELISA, fibroblasts by hematoxylin-eosin staining, and types I and III collagen by ELISA. Staining for VEGF was found in many types of cell including fibroblasts. The amount of VEGF in the skin of laser-treated areas had increased significantly compared to that in the control areas on days 1 and 3 (P < 0.05, P < 0.01, respectively), then decreased by day 7 after treatment and returned to the baseline level. The number of fibroblasts in the skin of the laser-treated areas had increased significantly compared to that in control areas on days 3, 7, 14, 28 and 56 after irradiation (P < 0.05, P < 0.01, P < 0.01, P < 0.01, P < 0.01, respectively). The amount of type I collagen was significantly higher in the skin of the laser-treated areas compared to that in control areas from day 28 to day 56 (P < 0.05, respectively), and type III collagen was significantly higher from day 3 to day 56 (P < 0.05, P < 0.05, P < 0.05, P < 0.05, P < 0.01, respectively). There was a positive correlation between the level of VEGF and fibroblast proliferation early stage after laser treatment (r = 0.853, P < 0.01), but there was no correlation after the first week (r = -0.124, P > 0.05). The amounts of type I and III collagen showed no significant correlations with the expression of VEGF in the late stages after laser treatment (r = 0.417, P > 0.05 and r = 0.340, P > 0.05, respectively). The results suggest that VEGF might be mainly involved in the early stages of wound healing, including the stages of acute inflammation, fibroblast proliferation and vessel formation induced by fractional CO(2) laser resurfacing.

Genetic diversity and linkage disequilibrium in Chinese bread wheat (Triticum aestivum L.) revealed by SSR markers.

Two hundred and fifty bread wheat lines, mainly Chinese mini core accessions, were assayed for polymorphism and linkage disequilibrium (LD) based on 512 whole-genome microsatellite loci representing a mean marker density of 5.1 cM. A total of 6,724 alleles ranging from 1 to 49 per locus were identified in all collections. The mean PIC value was 0.650, ranging from 0 to 0.965. Population structure and principal coordinate analysis revealed that landraces and modern varieties were two relatively independent genetic sub-groups. Landraces had a higher allelic diversity than modern varieties with respect to both genomes and chromosomes in terms of total number of alleles and allelic richness. 3,833 (57.0%) and 2,788 (41.5%) rare alleles with frequencies of <5% were found in the landrace and modern variety gene pools, respectively, indicating greater numbers of rare variants, or likely new alleles, in landraces. Analysis of molecular variance (AMOVA) showed that A genome had the largest genetic differentiation and D genome the lowest. In contrast to genetic diversity, modern varieties displayed a wider average LD decay across the whole genome for locus pairs with r(2)>0.05 (P<0.001) than the landraces. Mean LD decay distance for the landraces at the whole genome level was <5 cM, while a higher LD decay distance of 5-10 cM in modern varieties. LD decay distances were also somewhat different for each of the 21 chromosomes, being higher for most of the chromosomes in modern varieties (<5 ∼ 25 cM) compared to landraces (<5 ∼ 15 cM), presumably indicating the influences of domestication and breeding. This study facilitates predicting the marker density required to effectively associate genotypes with traits in Chinese wheat genetic resources.

Follow-up study identifies two novel susceptibility loci PRKCB and 8p11.21 for systemic lupus erythematosus.

OBJECTIVE: We have performed a large-scale replication study based on our previous genome-wide association study (GWAS) of SLE in the Chinese Han population to further explore additional genetic variants affecting susceptibility to SLE. METHODS: Thirty-eight single nucleotide polymorphisms from our GWAS were genotyped in two additional Chinese Han cohorts (total 3152 cases and 7050 controls) using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate. RESULTS: Association evidence for rs16972959 (PRKCB at 16p11.2) and rs12676482 (8p11.21) with SLE was replicated independently in both replication cohorts (P < 0.05), showing high significance for SLE in combined all 4199 cases and 8255 controls of Chinese Han [rs16972959: odds ratio (OR) = 0.81; 95% CI 0.76, 0.87; P(combined) = 1.35 × 10(-9); rs12676482: OR = 1.26; 95% CI 1.15, 1.38; P(combined) = 6.68 × 10(-7)). PRKCB is related to the established SLE immune-related pathway (NF-κB) and 8p11.21 contains important candidate genes such as IKBKB and DKK4. IKBKB is a critical component of NF-κB and DKK4 is an inhibitor of canonical Wnt signalling pathway. Interestingly, PRKCB is required for recruiting IKBKB into lipid rafts, up-regulating NF-κB-dependent survival signal. CONCLUSIONS: Our findings provided novel insights into the genetic architecture of SLE and emphasized the contribution of multiple variants of modest effect. Further study focused on PRKCB, 8p11.21, should advance our understanding on the pathogenesis of SLE.

The wheat (T. aestivum) sucrose synthase 2 gene (TaSus2) active in endosperm development is associated with yield traits.

Sucrose synthase catalyzes the reaction sucrose + UDP → UDP-glucose + fructose, the first step in the conversion of sucrose to starch in endosperm. Previous studies identified two tissue-specific, yet functionally redundant, sucrose synthase (SUS) genes, Sus1 and Sus2. In the present study, the wheat Sus2 orthologous gene (TaSus2) series was isolated and mapped on chromosomes 2A, 2B, and 2D. Based on sequencing in 61 wheat accessions, three single-nucleotide polymorphisms (SNPs) were detected in TaSus2-2B. These formed two haplotypes (Hap-H and Hap-L), but no diversity was found in either TaSus2-2A or TaSus2-2D. Based on the sequences of the two haplotypes, we developed a co-dominant marker, TaSus2-2B ( tgw ), which amplified 423 or 381-bp fragments in different wheat accessions. TaSus2-2B ( tgw ) was located between markers Xbarc102.2 and Xbarc91 on chromosome 2BS in a RIL population from Xiaoyan 54 × Jing 411. Association analysis suggested that the two haplotypes were significantly associated with 1,000 grain weight (TGW) in 89 modern wheat varieties in the Chinese mini-core collection. Mean TGW difference between the two haplotypes over three cropping seasons was 4.26 g (varying from 3.71 to 4.94 g). Comparative genomics analysis detected major kernel weight QTLs not only in the chromosome region containing TaSus2-2B (tgw), but also in the collinear regions of TaSus2 on rice chromosome 7 and maize chromosome 9. The preferred Hap-H haplotype for high TGW underwent very strong positive selection in Chinese wheat breeding, but not in Europe. The geographic distribution of Hap-H was perhaps determined by both latitude and the intensity of selection in wheat breeding.

Association analyses identify six new psoriasis susceptibility loci in the Chinese population.

We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 × 10⁻8) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 × 10⁻²¹) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 × 10⁻³ and P = 7.9 × 10⁻³, respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 × 10⁻³ and P = 1.5 × 10⁻³, respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis.

Involvement of mTOR and survivin inhibition in tamoxifen-induced apoptosis in human hepatoblastoma cell line HepG2.

Patients with advanced hepatocellular carcinoma (HCC) have shown to benefit from tamoxifen treatment. The mechanisms of tamoxifen effects in HCC, however, are not yet clearly understood. The PI3K/Akt/mTOR signal pathway is involved in cell proliferation, tumorigenesis, and apoptosis. Over-expression of survivin has played an important role in leading to antiapoptosis. The current study investigated changes in mTOR pathway and survivin expression in hepatocarcinoma cell line HepG2 treated with tamoxifen. We detected apoptosis of hepatocarcinoma cells by flow cytometry assay. Survivin transcription level and p70S6k was demonstrated by PCR, dual-luciferase reporter assay and western blot analysis respectively. Our results are showed as follows: tamoxifen leads to apoptosis of the cells, and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6 kinase. Twenty micromoles tamoxifen treatment significantly depresses transcription of survivin mRNA. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduce survivin protein level but did not affect survivin transcription, which indicated that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells. Our results suggest that tamoxifen down-regulate survivin expression in HepG2 cells is mediated by transcriptional and posttranscriptional level via PI3K/Akt/mTOR pathway to induce apoptosis.

Tamoxifen inhibits proliferation and induces apoptosis in human hepatocellular carcinoma cell line HepG2 via down-regulation of survivin expression.

Tamoxifen has been used in patients with hepatocellular carcinoma (HCC). However, its inhibitory mechanism remains unknown. In current study, we evaluated the effect of tamoxifen on the estrogen receptor-alpha-negative HCC cell proliferation, apoptosis and expression of survivin which had been known to play an important role in promotion of cellular proliferation as well as inhibition of apoptosis in cancer cells. HepG2 cells were incubated with tamoxifen (0.1, 1, 10, or 20 microM) for up to 72 h. Cell proliferation was assessed, flow cytometric analysis was performed, and survivin expression was detected. Our results are showed as follows. Ten or 20 microM tamoxifen induced a reduction of cell proliferation. Basically reduction of proliferation was related to an increase in the fraction of G0/1-phase. When tamoxifen was administrated at higher concentration (20 microM), the increase of the relative apoptosis appeared with a delay, augmenting the effect of tamoxifen on cell proliferation. When apoptosis was induced, a significant depression of survivin expression preceded. In conclusion, the tamoxifen decreasing cell proliferation and induction of apoptosis of HepG2 cells depends on drug concentration, which is due to cytostatic and cytocide effects, the latter may be mediated by a down-regulation of survivin expression.