Novel liquid fermentation medium of Cordyceps militaris and optimization of hydrothermal reflux extraction of cordycepin.

In this study, we developed a novel liquid fermentation medium of Cordyceps militaris using pupa powder and wheat bran as nitrogen resources instead of the traditionally used peptone. This process not only reduced the cost by approximately 50%, but increased production by over 30%. Then, we explored a method to extract and purify cordycepin by combining hydrothermal reflux extraction with macroporous resin adsorption, which is inexpensive and suitable for the industrial production. The optimum conditions for hydrothermal reflux were extracting three times at 95 °C with 1:10 sample-to-water ratio, and the cordycepin purity with macroporous resin HPD-100 reached 95.23%.[Formula: see text].

HprKXcc is a serine kinase that regulates virulence in the Gram-negative phytopathogen Xanthomonas campestris.

The HprK serine kinase is a component of the phosphoenolpyruvate phosphotransferase system (PTS) of bacteria that generally regulates catabolite repression through phosphorylation/dephosphorylation of the PTS protein PtsH at a conserved serine residue. However, many bacteria do not encode a complete PTS or even have an HprK homologue. Xanthomonas campestris pv. campestris (Xcc) is a pathogen that cause black rot disease in crucifer plants and one of the few Gram-negative bacteria that encodes a homologue of HprK protein (herein HprKXcc ). To gain insight into the role of HprKXcc and other PTS-related components in Xcc we individually mutated and phenotypically assessed the resulting strains. Deletion of hprK Xcc demonstrated its requirement for virulence and other diverse cellular processes associated including extracellular enzyme activity, extracellular-polysaccharide production and cell motility. Global transcriptome analyses revealed the HprKXcc had a broad regulatory role in Xcc. Additionally, through overexpression, double gene deletion and transcriptome analysis we demonstrated that hprK Xcc shares an epistatic relationship with ptsH. Furthermore, we demonstrate that HprKXcc is a functional serine kinase, which has the ability to phosphorylate PtsH. Taken together, the data illustrates the previously unappreciated global regulatory role of HprKXcc and previously uncharacterized PTS components that control virulence in this pathogen.

Association between PIN1 promoter polymorphisms and risk of nasopharyngeal carcinoma.

Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) plays an important role in cell transformation and oncogenesis. Association between PIN1 promoter polymorphisms and cancer risk was reported in several cancers. This study aimed to evaluate the association between two single nucleotide polymorphisms (SNPs, -667T>C, rs2233679 and -842G>C, rs2233678) on PIN1 promoter and risk of nasopharyngeal carcinoma (NPC). The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism in a total of 334 native Chinese subjects consisting of 178 cases and 156 controls. The results indicated that the -667CT heterozygote and -667CC homozygote exhibited a significantly decreased risk of nasopharyngeal carcinoma when compared with -667TT homozygote (OR = 0.639, 95% CI = 0.452-0.903, p = 0.011 for -667CT; and OR = 0.441, 95% CI = 0.213-0.915, p = 0.038 for -667CC, respectively). In the -842G>C polymorphism, compared with -842GG homozygote, only -842CG heterozygote but not -842CC homozygote had a significantly decreased risk of nasopharyngeal carcinoma (OR = 0.465, 95% CI = 0.249-0.871, p = 0.010). Genotype in the two SNPs in patients showed no significant associations with the clinicopathologic features examined. Our study showed that the minor genotypes of PIN1 promoter (-667CT, -667CC and -842CG) were associated with decreased risk of NPC in a Chinese population, suggested that PIN1 promoter polymorphisms might play an important role in NPC carcinogenesis.

Untargeted Metabolomics and Physicochemical Analysis Revealed the Quality Formation Mechanism in Fermented Milk Inoculated with Lactobacillus brevis and Kluyveromyces marxianus Isolated from Traditional Fermented Milk.

Traditional fermented milk from the western Sichuan plateau of China has a unique flavor and rich microbial diversity. This study explored the quality formation mechanism in fermented milk inoculated with Lactobacillus brevis NZ4 and Kluyveromyces marxianus SY11 (MFM), the dominant microorganisms isolated from traditional dairy products in western nan. The results indicated that MFM displayed better overall quality than the milk fermented with L. brevis NZ4 (LFM) and K. marxianus SY11 (KFM), respectively. MFM exhibited good sensory quality, more organic acid types, more free amino acids and esters, and moderate acidity and ethanol concentrations. Non-targeted metabolomics showed a total of 885 metabolites annotated in the samples, representing 204 differential metabolites between MFM and LFM and 163 between MFM and KFM. MFM displayed higher levels of N-acetyl-L-glutamic acid, cysteinyl serine, glaucarubin, and other substances. The differential metabolites were mainly enriched in pathways such as glycerophospholipid metabolism, arginine biosynthesis, and beta-alanine metabolism. This study speculated that L. brevis affected K. marxianus growth via its metabolites, while the mixed fermentation of these strains significantly changed the metabolism pathway of flavor-related substances, especially glycerophospholipid metabolism. Furthermore, mixed fermentation modified the flavor and quality of fermented milk by affecting cell growth and metabolic pathways.

ZNF804A and schizophrenia susceptibility in Asian populations.

ZNF804A, a recently identified risk gene for schizophrenia, has been extensively investigated and the principle finding for this locus has been the association with SNP rs1344706 in populations of European ancestries. However, in Asian populations, only a few studies have been conducted for rs1344706 and the results were inconsistent. Here, we studied rs1344706 and schizophrenia susceptibility in multiple Asian case-control samples (10 Chinese and 2 Japanese samples; N = 21,062), and the meta-analyses indicated non-significant association of rs1344706 with schizophrenia (P = 0.26), suggesting the same SNP identified in European samples is not predisposing risk in Asians. Further genotyping and association analyses of a set of SNPs spanning the entire genomic region of ZNF804A (520 kb) identified no association except for SNP rs359895 (P = 7.8 x 10(-5) , N = 5,172), a newly reported risk SNP located in the ZNF804A promoter region with functional implications. This suggests that ZNF804A may also contribute to schizophrenia susceptibility in Asians although the risk SNP is different from that in Europeans, and it was supported by the detected up-regulation of ZNF804A mRNA expression in the blood cells of Chinese schizophrenia patients compared with normal controls (P = 0.004). Additionally, the linkage disequilibrium (LD) structure analyses using data from HapMap indicated distinct LD blocks across ZNF804A between Chinese and Europeans, which may explain the different association patterns between them, and also highlight the compounding difficulty of genetic studies of complex diseases like schizophrenia when studying multiple ethnic populations.

Fixation and reconstruction of severe tibial shaft fractures with vascularized fibular grafting.

INTRODUCTION: Based on the considerable experience for management of combined bone and composite soft-tissue defects in the limbs by free vascularized fibula or osteocutaneous fibular flap grafting, the authors present the effective alternative for management of the severe comminuted tibial shaft fractures in one-stage reconstructive technique. METHOD: Twenty-six patients were male and 12 were female, and their mean age was 32 years (range 15-57 years). Ten tibial shaft fractures were closed and 28 were open. Based on the AO classification, there were 12 group C1 fractures and 24 group C3 fractures according to the fracture pattern and degree of comminution. RESULTS: With the exception of eight cases that were delayed for 3-5 days for primary treatment in another hospital, 30 cases were treated on an emergency basis within an average of 12 h since the initial injury (range 6-22). Normal healing occurred in 31 fractures with a mean healing time of 21 weeks (range 18-24 weeks). Delayed union in 7 with a mean of 32 weeks (range 28-41 weeks), and there were no nonunion and infections. The vascularized fibula allows for fast bone fusion. In this context, the grafted fibula segment appeared to be a valuable reconstructive tool that offered good fracture stabilization and vascularised bone graft. CONCLUSION: The attached fibular flap can also provide a large piece of mobile skin to cover the soft-tissue defect in grade III open-tibial fractures. It demonstrates that this early free vascularized fibula graft is a useful and effective option for treating the severe comminuted tibial shaft fractures.

Involvement of kisspeptin in androgen-induced hypothalamic endoplasmic reticulum stress and its rescuing effect in PCOS rats.

Endoplasmic reticulum (ER) stress, with adaptive unfolded protein response (UPR), is a key link between obesity, insulin resistance and type 2 diabetes, all of which are often present in the most common endocrine-metabolic disorder in women of reproductive age, polycystic ovary syndrome (PCOS), which is characterized with hyperandrogenism. However, the link between excess androgen and endoplasmic reticulum (ER) stress/insulin resistance in patients with polycystic ovary syndrome (PCOS) is unknown. An unexpected role of kisspeptin was reported in the regulation of UPR pathways and its involvement in the androgen-induced ER stress in hypothalamic neuronal cells. To evaluate the relationship of kisspeptin and ER stress, we detected kisspeptin and other factors in blood plasm of PCOS patients, rat models and hypothalamic neuronal cells. We detected higher testosterone and lower kisspeptin levels in the plasma of PCOS than that in non-PCOS women. We established a PCOS rat model by dihydrotestosterone (DHT) chronic exposure, and observed significantly downregulated kisspeptin expression and activated UPR pathways in PCOS rat hypothalamus compared to that in controls. Inhibition or knockdown of kisspeptin completely mimicked the enhancing effect of DHT on UPR pathways in a hypothalamic neuronal cell line, GT1-7. Kp10, the most potent peptide of kisspeptin, effectively reversed or suppressed the activated UPR pathways induced by DHT or thapsigargin, an ER stress activator, in GT1-7 cells, as well as in the hypothalamus in PCOS rats. Similarly, kisspeptin attenuated thapsigargin-induced Ca2+ response and the DHT- induced insulin resistance in GT1-7 cells. Collectively, the present study has revealed an unexpected protective role of kisspeptin against ER stress and insulin resistance in the hypothalamus and has provided a new treatment strategy targeting hypothalamic ER stress and insulin resistance with kisspeptin as a potential therapeutic agent.

Simultaneous radius and ulna reconstruction with folded free vascularized fibula transfer: case report.

We report 1 case of successful treatment of radius and ulna nonunion by a folded vascularized fibular graft, in which 2 parallel fibular struts remained connected by the periosteum and peroneal vessels, and another case of infected nonunion of the ulna and radius with osseous and soft tissue defects treated by a free fibular osteoseptocutaneous flap with folded fibular graft in a 1-stage procedure.

Elevation of antimüllerian hormone in women with polycystic ovary syndrome undergoing assisted reproduction: effect of insulin.

OBJECTIVE: To measure blood and follicular antimüllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technologies (ART) and to examine the direct action of insulin on AMH expression in human granulosa cells. DESIGN: Prospective clinical and experimental study. SETTING: University Hospital-based laboratory. PATIENT(S): Women with (n = 86) and without (n = 172) PCOS in ART. INTERVENTION(S): Blood, follicular fluid, and luteinized granulosa cells were collected from PCOS and non-PCOS women in ART. MAIN OUTCOME MEASURE(S): Hormone levels in blood and fluid, and gene expression in granulosa cells. RESULT(S): Serum levels of AMH were elevated and inversely correlated with embryo cleavage rate in PCOS women in ART. Significant higher levels of AMH were also found in small and large follicles collected from PCOS women compared with non-PCOS women. Luteinized granulosa cells from PCOS women showed higher expression of AMH and its receptor AMHR2. Direct effect of insulin in increasing the expression of AMH in the isolated luteinized granulosa cells was observed, with the PCOS granulosa cells responding to a high dose of insulin. Cotreatment with AMH attenuated insulin-induced aromatase expression in the luteinized granulosa cells. CONCLUSION(S): These results suggest that insulin may contribute to AMH elevation in PCOS and that AMH counteracts insulin-promoted aromatase expression in granulosa cells.

Properties comparison between free and immobilized wheat esterase using glass fiber film.

In this paper, the catalytic performance of non-purified esterase from wheat bran immobilized on glass fibre membrane carrier is established, the immobilization conditions observed were enzyme 1 mL, phosphate buffer 3 mL (pH 7.0), immobilization time 1 h, immobilization temperature 29 °C. After carrier functionalization some characteristics of immobilized enzyme were studied, the results showed that immobilized enzyme presenting improved characteristic than that of free enzyme. The optimum pH for free and immobilized enzymes were found to be 8 and 7, respectively. As for optimum temperature for free and immobilized enzymes were observed to be 30 °C and 40 °C, respectively. When the enzyme was immobilized on glass fibre membranes, its Km increased about 7 times. In addition, storage and thermal stability of the free wheat esterase were increased by as a result of membrane immobilization, after 12 days of storage, the immobilized enzyme still retained about 91.10% of its original activity at 4 °C, indicating a great potential in industrial application.

Identification of active compound combination contributing to anti-inflammatory activity of Xiao-Cheng-Qi Decoction via human intestinal bacterial metabolism.

Human intestinal bacteria play an important role in the metabolism of herbal medicines, leading to the variations in their pharmacological profile. The present study aimed to investigate the metabolism of Xiao-Cheng-Qi decoction (XCQD) by human intestinal bacteria and to discover active component combination (ACC) contributing to the anti-inflammatory activity of XCQD. The water extract of XCQD was anaerobically incubated with human intestinal bacteria suspensions for 48 h at 37 °C. A liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) method was performed for identification of the metabolites. In addition, the anti-inflammatory effects of XCQD and biotransformed XCQD (XCQD-BT) were evaluated in vitro with cytokines in RAW264.7 cells induced by lipopolysaccharide (LPS). A total of 51 compounds were identified in XCQD and XCQD-BT. Among them, 20 metabolites were proven to be transformed by human intestinal bacteria. Significantly, a combination of 14 compounds was identified as ACC from XCQD-BT, which was as effective as XCQD in cell models of inflammation. In conclusion, this study provided an applicable method, based on intestinal bacterial metabolism, for identifying combinatory compounds responsible for a certain pharmacological activity of herbal medicines.

The role of eukaryotic translation initiation factor 6 in tumors.

Eukaryotic translation initiation factor 6 (eIF6) affects the maturation of 60S ribosomal subunits. Found in yeast and mammalian cells, eIF6 is primarily located in the cytoplasm of mammalian cells. Emerging evidence has demonstrated that the dysregulated expression of eIF6 is important in several types of human cancer, including head and neck carcinoma, colorectal cancer, non-small cell lung cancer and ovarian serous adenocarcinoma. However, the molecular mechanisms by which eIF6 functions during tumor formation and progression remain elusive. The present review focuses on recent progress in terms of the mechanisms and functions of eIF6 in human tumorigenesis or cancer cell lines, along with the signal transduction pathways in which this novel translation initiation factor may participate. Oncogenic Ras activates Notch-1 and promotes transcription of eIF6 via a recombining binding protein suppressor of Hairless-dependent mechanism. In addition, overexpression of eIF6 results in aberrant activation of the Wnt/ß-catenin signaling pathway. Similarly, overexpressed eIF6 regulates its downstream modulator, cell division control protein 42, which in turn affects oncogenesis. Finally, the potential of eIF6 as a biomarker for diagnosis of cancer is also discussed in the present review.

Metabolic profile and underlying improved bio-activity of Fructus aurantii immaturus by human intestinal bacteria.

Fructus aurantii immaturus (FAI) is the dried young fruit of Citrus aurantium L. or Citrus sinensis L. Osbeck. The purpose of this paper was to investigate the metabolic fate of FAI upon incubation with human intestinal bacteria, meanwhile to evaluate the antioxidant and anti-inflammatory activities of FAI and the transformed Fructus aurantii immaturus (TFAI). The water extract of FAI was anaerobically incubated with human intestinal bacterial suspensions for 48 h at 37 °C. Liquid chromatography-hybridised with quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) was applied to identify FAI metabolites. A total of 45 compounds were identified in FAI, eleven of which were metabolized by human intestinal bacteria. Nine major metabolites were identified as eriodictyol, naringenin, hesperetin, luteolin, apigenin, chryseriol, isosakuranetin, phloretin and diosmetin. The metabolic profile of FAI was elucidated on the basis of metabolite information. We found that the concentrations of acetic, propionic and butyric acids in FAI culture were all increased during fermentation relative to those of the control. Further bioactive evaluations showed that TFAI exhibited more potent antioxidant and anti-inflammatory abilities than FAI in vitro. Additionally, in vivo experiment confirmed that FAI significantly attenuated the blood endotoxin and TNF-α levels in the conventional rats compared to those of pseudo-germ-free (PGF) rats. This study revealed that metabolites may play a key role in the antioxidant and anti-inflammatory capacities of FAI.

The activity of Hou-Po-Da-Huang-Tang is improved through intestinal bacterial metabolism and Hou-Po-Da-Huang-Tang selectively stimulate the growth of intestinal bacteria associated with health.

Hou-Po-Da-Huang Tang (HPDHT) was used for the treatment of intestinal tract diseases in China. However, the underlying mechanisms via the intestinal bacteria remain largely unclear. Therefore, the aim of this study was to evaluate the metabolism of HPDHT by the human intestinal bacteria and its modulating effect on the intestinal bacteria. As a result, a total of 34 compounds were identified in HPDHT and transformed HPDHT (T-HPDHT). Among them, 12 metabolites were proved to be transformed by human intestinal bacteria. In vitro assays showed that T-HPDHT exhibited more significant elevation of free radical scavenging activity and suppression on the production of nitric oxide (NO) and TNF-α when comparing to HPDHT. Additionally, in vivo experiment confirmed that HPDHT significantly increased activity of superoxide dismutase (SOD), attenuated the malondialdehyde (MDA) and TNF-α levels in the conventional rats compared with that of pseudo germ-free (PGF) rats. In addition, HPDHT could significantly enhance the mean counts of Bifidobacterium and Lactobacillus and inhibit the growth of Clostridium, and Enterobacteriaceae, relative to controls. Due to the transformation of HPDHT being dependent on the bacterial strain, the effect of HPDHT on the selective growth of Bifidobacterium bifidum 29521 and Lactobacillus plantarum 8014 was evaluated. The kinetic parameters of microbial growth and prebiotic activity scores indicated that HPDHT could selectively stimulate the growth of the strains Bifidobacterium bifidum 29521 and Lactobacillus plantarum 8014. Taken together, metabolism of HPDHT by intestinal bacteria is a critical step towards the emergence of their anti-oxidation, anti-inflammation and prebiotic activities. This study provided valuable information for further pharmacological research on HPDHT.

Effect of Cultivar, Temperature, and Environmental Conditions on the Dynamic Change of Melatonin in Mulberry Fruit Development and Wine Fermentation.

High levels of melatonin have been reported in various foods but not in mulberry or its wine. This study investigated the dynamic changes of melatonin levels during mulberry fruit development and ethanol fermentation of 2 different colored mulberry cultivars ("Hongguo2Ë® Morus nigra, black and "BaiyuwangË® Morus alba, white) at 2 fermentation temperatures (16 and 25 °C). Our results showed that the melatonin level increased in the beginning of mulberry development but decreased in the end. The MnTDC gene expression level correlated with melatonin production, which implied that TDC may be the rate-limiting enzyme of the melatonin biosynthetic process in mulberries. During mulberry fermentation, the melatonin concentration increased rapidly in the beginning and then decreased gradually. Low temperature delayed the melatonin production during fermentation. A relatively high level of melatonin was found in "Hongguo2Ë® compared with "BaiyuwangË® during fruit development and fermentation. The variation of melatonin correlated with the ethanol production rate, suggesting that melatonin may participate in physiological regulation of Saccharomyces cerevisiae during the fermentation stage.

In vitro biotransformation of red ginseng extract by human intestinal microflora: metabolites identification and metabolic profile elucidation using LC-Q-TOF/MS.

Ginseng is an important and widely used herbal medicine in Asia and has gained popularity in the western countries. Ginseng products are usually administered orally, after which their complicated components are brought into contact with intestinal microflora in the alimentary tract and metabolized. The metabolic investigation of ginseng in intestinal tract is necessary for elucidating its pharmacological activities. However, most of the reports about the metabolism of ginseng with intestinal microflora are focused on single ginseng saponin with the whole action of ginseng extract ignored. In the present paper, in vitro biotransformation of red ginseng extract by human intestinal microflora was conducted, and a rapid liquid chromatography with time-of-flight mass spectrometry (LC-Q-TOF/MS) method was used for rapid identification of the metabolites and metabolic profile of ginseng saponins. A total of 37 ginseng saponins in red ginseng extract were characterized, 17 of which were assessed to be metabolized by human intestinal microflora. Also, 30 metabolites, mostly deglycosylated, were detected and identified in the biotransformed red ginseng extract, including 4 original ingredients of red ginseng, 6 ginsenoside lactate esters, and 2 glycosylated metabolites. The metabolic profile of ginseng saponins biotransformed by human intestinal microflora was elucidated based on the metabolite information. The results indicated that deglycosylation was the major metabolic pathway of saponins in red ginseng. The esterification and glycosylation reaction also occurred during the biotransformation. Our study indicated that there was some differences in the biotransformation of single ginseng saponin and red ginseng extract. It must be noted that the ginsenoside lactate esters were firstly found in the metabolites of ginsenosides.

[Application of the tension skin flap with different shapes in the pedicle of the reverse neurocutaneous island flap].

OBJECTIVE: To investigate the effects of the tension skin flap with different shapes on the transplantation of the reverse neurocutaneous island flap. METHODS: From January 2006 to January 2012,there were 21 patients in the study (including 15 males and 6 females), and aged from 14 to 58 years old (35 years old on average). Tension skin flaps with different shapes (triangle ,round and ellipse) were used to improve the blood supply of the reverse neurocutaneous island flap. The tension skin flaps in the pedicle were designed triangularly (10 patients), spherically (8 patients) or elliptically (3 patients). There were 5 patients with defects in the hand (the size from 5.0 cm x 2.0 cm to 8.0 cm x 5.0 cm), and 16 patients with defects in the foot and inferior segment of leg, or around the ankle (the size from 6.0 cm x 4.0 cm to 13.0 cm x 7.0 cm). And all the patients were with the tendon and bone exposed. All the flaps were reversal transplanted, including 5 dorsal neurocutaneous flaps of foot, 4 superficial peroneal neurocutaneous flaps, 4 saphenous neurocutaneous flaps, 3 sural neurocutaneous flaps, 2 superficial radial neurocutaneous flaps, 3 lateral neurocutaneous flaps of forearm. And the survival rate, appearance and sensory recovery of the flaps were analyzed. RESULTS: The distant part of the reversed sural neurocutaneous island flap in 1 case necrosized and healed after dressing change. The other flaps survived entirely, and the donor site all healed primarily. The follow-up time was from 3 months to 2 years (averaged 7 months), and all the flaps had recovered pain and warm sensation with perfect appearance. CONCLUSION: The tension skin flap in the pedicle can enhance the blood supply and promote survival rate of the reverse neurocutaneous island flap, and can also improve its appearance.

Prolyl isomerase Pin1 regulated signaling pathway revealed by Pin1 +/+ and Pin1 -/- mouse embryonic fibroblast cells.

Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1) plays a key role in a number of diseases including cancer and Alzheimer disease. Previous studies have identified a wide range of phosphoproteins as Pin1 substrates. Related pathways were analyzed separately. The aim of this study was to provide a comprehensive picture involving Pin1 regulation. A genome-wide mRNA expression microarray was carried out using the RNA isolation from Pin1 (+/+) and Pin1 (-/-) mouse embryonic fibroblast (MEF) cells. Signaling pathways regulated by Pin1 were analyzed with the utility of KEGG pathway and GO annotation. An expression pattern regulated by Pin1 was revealed. A total of 606 genes, 375 being up-regulated and 231 down-regulated, were differentially expressed when comparing Pin1 +/+ to Pin1 -/- MEF cells. Totally 48 pathways were shown to be regulated by Pin1 expression in KEGG pathway analysis. In the GO annotation system, 19 processes on biological processes, 15 processes on cellular components, and 18 processes on molecular functions were found to be in the regulation of Pin1 expression. Pathways related to immune system and cancer showed most significant association with Pin1 regulation. Pin1 is an important regulator in a wide range of signaling pathways that were related to immune system and cancer.

Analysis of common genetic variants identifies RELN as a risk gene for schizophrenia in Chinese population.

UNLABELLED: Abstract Objectives. Several lines of evidence have shown that both RELN mRNA and protein are possibly down-regulated in the brain of schizophrenia patients. Recent association studies in European populations suggested RELN as a risk gene for schizophrenia. In this study, we test if RELN contributes to the risk of schizophrenia in Chinese population. Methods. We conducted case-control association analysis of 19 representative single nucleotide polymorphisms (SNPs) spanning the entire region of RELN in two independent Han Chinese samples from southwestern China (the Kunming sample and the Yuxi sample). Results. We identified six SNPs significantly associated with schizophrenia in the Kunming sample and four of them remained significant in the combined samples (the P values range from 0.006 to 4.0 × 10(-5)). Haplotype analysis also suggested significant associations for the haplotypes incorporating the six significant SNPs (global P < 1.0 × 10(-5)). Additionally, we also observed several other haplotypes (defined by a different set of SNPs) significantly associated with schizophrenia in the Kunming sample. However, the reported association of rs7341475 in Ashkenazi Jews was not significant in Han Chinese. CONCLUSIONS: Our findings demonstrate that RELN is a susceptibility gene for schizophrenia in Chinese population, and it is likely a common risk gene for schizophrenia in major populations worldwide.

Activating transcription factor 1 is a prognostic marker of colorectal cancer.

OBJECTIVE: Identifying cancer-related genes or proteins is critical in preventing and controlling colorectal cancer (CRC). This study was to investigate the clinicopathological and prognostic value of activating transcription factor 1 (ATF1) in CRC. METHODS: Protein expression of ATF1 was detected using immunohistochemistry in 66 CRC tissues. Clinicopathological association of ATF1 in CRC was analyzed with chi-square test or Fisher's exact test. The prognostic value of ATF1 in CRC is estimated using the Kaplan-Meier analysis and Cox regression models. RESULTS: The ATF1 protein expression was significantly lower in tumor tissues than corresponding normal tissues (51.5% and 71.1%, respectively, P = 0.038). No correlation was found between ATF1 expression and the investigated clinicopathological parameters, including gender, age, depth of invasion, lymph node status, metastasis, pathological stage, vascular tumoral emboli, peritumoral deposits, chemotherapy and original tumor site (all with P > 0.05). Patients with higher ATF1 expression levels have a significantly higher survival rate than that with lower expression (P = 0.026 for overall survival, P = 0.008 for progress free survival). Multivariate Cox regression model revealed that ATF1 expression and depth of invasion were the predictors of the overall survival (P = 0.008 and P = 0.028) and progress free survival (P = 0.002 and P = 0.005) in CRC. CONCLUSIONS: Higher ATF1 expression is a predictor of a favorable outcome for the overall survival and progress free survival in CRC.