VPA inhibits renal cancer cell migration by targeting HDAC2 and down-regulating HIF-1α.

Cell migration plays major roles in human renal cancer-related death, but the molecular mechanisms remain unclear. Valproic acid (VPA) is a broad-spectrum inhibitor of class I and II histone deacetylases and shows great anticancer activity in a variety of human cancers. In this study, we found that VPA significantly inhibited cell migration but not proliferation of human renal cancer ACHN cells. Mechanistic studies found that VPA significantly inhibited the expression of HIF-1α. Knockdown of HIF-1α could obviously inhibited cell migration, while over-expression of HIF-1α markedly rescued the inhibition of VPA on cell migration. Further studies found that knockdown of HDAC2 completely mimicked the effects of VPA on HIF-1α and cell migration, and over-expression of HIF-1α could also rescue the effects of HDAC2 knockdown on cell migration. Collectively, these results indicated that the potential of specific inhibition of HDAC2 by small molecular chemicals may lead to future therapeutic agents in human renal cancer treatment.

Effect of Food Restriction on Food Grinding in Brandt's Voles.

Food grinding is supposed to be influenced by multiple factors. However, how those factors affecting this behavior remain unclear. In this study, we investigated the effect of food restriction on food grinding in Brandt's voles (Lasiopodomys brandtii), as well as the potential role of the gut microbiota in this process, through a comparison of the variations between voles with different food supplies. Food restriction reduced the relative amount of ground food to a greater extent than it lowered the relative food consumption, and altered the abundance of Staphylococcus, Aerococcus, Jeotgalicoccus, and Un--s-Clostridiaceae bacterium GM1. Fecal acetate content for the 7.5 g-food supply group was lower than that for the 15 g-food supply group. Our study indicated that food restriction could effectively inhibit food grinding. Further, Un--s-Clostridiaceae bacterium GM1 abundance, Aerococcus abundance, and acetate content were strongly related to food grinding. Variations in gut microbial abundance and short-chain fatty acid content induced by food restriction likely promote the inhibition of food grinding. These results could potentially provide guidance for reducing food waste during laboratory rodent maintenance.

Effect of Group Density on the Physiology and Aggressive Behavior of Male Brandt's Voles (Lasiopodomys brandtii).

Xin Dai, Ling-Yu Zhou, Jie-Xia Cao, Yan-Qi Zhang, Feng-Ping Yang, Ai-Qin Wang, Wan-Hong Wei, and Sheng-Mei Yang (2018) Population density is well known to influence animal physiology and behavior. How population density affects the aggressive behavior of the Brandt's vole (Lasiopodomys brandtii) is, however, little known. The aim of this study was to investigate the effect of group density on physiologic responses and aggressive behavior of male Brandt's voles and their potential underlying neuro-mechanism. The results show that increasing group density led to elevated serum corticosterone levels and increased spleen weight; it also induced more male-male aggressive behavior. By contrast, it had a negative effect on body growth and the weight of testis and epididymis. Aging also increased male-male aggressive behavior. Higher density reduced mRNA levels of tryptophan hydroxylase 2 (TPH2), 5-hydroxytryptamine receptor 1A (5HT1A), and 5-hydroxytryptamine receptor 1B (5HT1B) in the amygdala and the dorsal raphe nucleus (DRN). Our results demonstrate that higher population density can intensify stress reactions and male-male aggressive behavior in Brandt's voles at the price of inhibiting body growth and reproduction. Serotonergic systems in the amygdala and the DRN may take part in the control of aggressive behavior among male voles. Our results provide novel insights into the neuro-mechanism underlying the influence of population density on aggressive behavior in Brandt's vole, and imply that aggressive behavior may play an important role in the population fluctuation of the animal.

Genome Size Diversity in Lilium (Liliaceae) Is Correlated with Karyotype and Environmental Traits.

Genome size (GS) diversity is of fundamental biological importance. The occurrence of giant genomes in angiosperms is restricted to just a few lineages in the analyzed genome size of plant species so far. It is still an open question whether GS diversity is shaped by neutral or natural selection. The genus Lilium, with giant genomes, is phylogenetically and horticulturally important and is distributed throughout the northern hemisphere. GS diversity in Lilium and the underlying evolutionary mechanisms are poorly understood. We performed a comprehensive study involving phylogenetically independent analysis on 71 species to explore the diversity and evolution of GS and its correlation with karyological and environmental traits within Lilium (including Nomocharis). The strong phylogenetic signal detected for GS in the genus provides evidence consistent with that the repetitive DNA may be the primary contributors to the GS diversity, while the significant positive relationships detected between GS and the haploid chromosome length (HCL) provide insights into patterns of genome evolution. The relationships between GS and karyotypes indicate that ancestral karyotypes of Lilium are likely to have exhibited small genomes, low diversity in centromeric index (CVCI) values and relatively high relative variation in chromosome length (CVCL) values. Significant relationships identified between GS and annual temperature and between GS and annual precipitation suggest that adaptation to habitat strongly influences GS diversity. We conclude that GS in Lilium is shaped by both neutral (genetic drift) and adaptive evolution. These findings will have important consequences for understanding the evolution of giant plant genomes, and exploring the role of repetitive DNA fraction and chromosome changes in a plant group with large genomes and conservation of chromosome number.

Complete chloroplast genome sequences of Lilium: insights into evolutionary dynamics and phylogenetic analyses.

Lilium is a large genus that includes approximately 110 species distributed throughout cold and temperate regions of the Northern Hemisphere. The species-level phylogeny of Lilium remains unclear; previous studies have found universal markers but insufficient phylogenetic signals. In this study, we present the use of complete chloroplast genomes to explore the phylogeny of this genus. We sequenced nine Lilium chloroplast genomes and retrieved seven published chloroplast genomes for comparative and phylogenetic analyses. The genomes ranged from 151,655 bp to 153,235 bp in length and had a typical quadripartite structure with a conserved genome arrangement and moderate divergence. A comparison of sixteen Lilium chloroplast genomes revealed ten mutation hotspots. Single nucleotide polymorphisms (SNPs) for any two Lilium chloroplast genomes ranged from 8 to 1,178 and provided robust data for phylogeny. Except for some of the shortest internodes, phylogenetic relationships of the Lilium species inferred from the chloroplast genome obtained high support, indicating that chloroplast genome data will be useful to help resolve the deeper branches of phylogeny.

Induced expression of DREB transcriptional factor and study on its physiological effects of drought tolerance in transgenic wheat.

Expression vector pBAC128F, which carries DREB transcriptional factor gene driven by drought inducing promoter rd29B and bar gene driven by CaMV 35S promoter and maize Adh1 gene first intron, was transferred into the explants of immature inflorescence and immature embryos of hexaploid winter wheat cv. 8901, 5-98, 99-92 and 104 by particle bombardment. More than 70 resistant transgenic plants were obtained. Genomic PCR and RNA dot blotting analyses showed that DREB gene had been integrated into wheat genome of the transgenic plants (T0 and T1) and was well expressed in offspring seed of different transgenic lines. The content of proline in leaves and seeds of T2 transgenic lines was analyzed. Among 16 tested transgenic lines, 10 transgenic lines exhibited more than two fold of proline level in leaves as compared with CK plants. Under drought condition, after stopping water for 15 days the leaves of transgenic lines were still green, while CK were faded. After rewatering for 10 days, the leaves of transgenic lines maintained their green, while all CK plants were dead. Our research suggested that introducing a novel DREB transcriptional factor into wheat is an effective way to improve its drought-tolerance ability.

Association of a SNP in SLC35F3 Gene with the Risk of Hypertension in a Chinese Han Population.

A recent study suggested that SLC35F3 which encoded a thiamine transporter was a new candidate gene for hypertension. The goal of this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) in the SLC35F3 gene and hypertension in a Chinese population. Sanger sequencing was performed in 93 samples to find SNPs in coding regions and intron-exon boundaries in the SLC35F3 gene. We found eight genetic variants in the coding regions of SLC35F3 and subsequently genotyped a non-synonymous variant rs34032258 (C > G) in 1060 hypertension patients and 1467 controls. After adjusting for age and gender, multivariate analysis of covariance showed that the variant was associated with hypertensive traits. In detail, diastolic blood pressure (DBP) was 8 mmHg higher, blood urea nitrogen was 12 mmol/L higher, and creatinine was 15 mmol/L lower in G/G group compared with C/C group (p = 0.007; 0.012 and 0.029, respectively). Further study suggested that C/G+G/G had higher DBP than C/C genotype in those whose DBP ≥ 90 mmHg (98.02 mmHg vs. 94.04 mmHg, p = 0.021). No significant difference has been found in systolic blood pressure between different genotypes. Additionally, in the subgroup of obesity, allele distribution of this variant has shown significant difference between hypertensive patients and normotensive controls (p = 0.018). In conclusion, we found that the rs34032258 in the SLC35F3 gene was associated with high blood pressure and may increase the risk of hypertension. The new hypertension-susceptibility locus may involve in the pathogenesis of hypertension and indicate some novel treatment implications.

Foxl1 inhibits tumor invasion and predicts outcome in human renal cancer.

UNLABELLED: The Forkhead Box L1 (Foxl1) transcription factor regulates epithelial proliferation and development of gastrointestinal tract, and has been implicated in gastrointestinal and pancreatic tumorigenesis. However, the role of Foxl1 in renal cancer development and progression remains to be elucidated. The study was conducted to investigate the expression of Foxl1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of Foxl1 in human ccRCC was further investigated in cell culture models. METHODS: Real-time quantitative PCR, western-blot, immunohistochemistry were used to explore Foxl1 expression in primary ccRCC clinical specimens and ccRCC cell lines. Foxl1 expression was up-regulated by over-expression vector in 786-O and ACHN cells, proliferation, cell cycle, migration and invasion were assayed. RESULTS: Foxl1 expression was down-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that Foxl1 expression was significantly correlated with tumor stage, lymph node metastasis, distant metastasis, clinical TNM stage (cTNM) and histological grade of renal cancer. The Kaplan-Meier survival curves revealed that low Foxl1 expression was associated with poor prognosis in ccRCC patients. Foxl1 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis. Mechanistic analyses demonstrated that over-expression of Foxl1 inhibits tumor cell growth, migration and invasion in renal cancer cells. CONCLUSIONS: These results suggest that Foxl1 expression is a candidate predictor of clinical outcome in patients with resected ccRCC and it plays an inhibitory role in renal tumor progression.

Argonaute 2 is up-regulated in tissues of urothelial carcinoma of bladder.

UNLABELLED: Argonaute 2 proteins (Ago2) have been demonstrated to be widely expressed and involved in post-transcriptional gene silencing and play key roles in carcinogenesis. However, its expression profile and prognostic value in urothelial carcinoma of the bladder (UCB) have not been investigated. METHODS: Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore Ago2 expression in UCBs and normal bladder tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of Ago2 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of Ago2 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blot when compared with their paired normal bladder tissues. Clinic pathological analysis was showed a significant correlation existed between the higher expression of Ago2 protein with the Histological grade, lymph node metastasis and Distant metastasis (P<0.05); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated Ago2 expression in cancer tissue predicted poorer overall survival (OS) compared with group in lower expression (62.2% VS 86.3%, P<0.05). Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of Ago2 was an independent prognostic factor in UCB. CONCLUSIONS: These results suggest that the aberrant expression of Ago2 in human UCB is possibly involved with tumorigenesis and development, and the Ago2 protein could act as a potential biomarker for prognosis assessment of bladder cancer. Further studies on the cellular functions of Ago2 need to address these issues.

Association study on the DLG4 gene and schizophrenia in the Chinese Han population.

BACKGROUND: Abnormal expressions of the N-methyl-D-aspartate receptor and its interacting postsynaptic density (PSD) molecules have been hypothesized to be involved in the pathophysiology of schizophrenia. Few studies have carried out association studies with DLG4 gene (coding PSD-95 protein) and sought to validate the results with Asian schizophrenia patients. PATIENTS AND METHODS: To further investigate the significance of DLG4 in Asian schizophrenic patients, we examined seven single-nucleotide polymorphisms (SNPs) within this gene in 1504 unrelated Chinese mainland individuals (893 patients and 611 controls). RESULTS: No association was found between these seven SNPs and schizophrenia within our sample. No significant differences in allele or genotype frequencies between schizophrenic paranoid patients and controls were found. CONCLUSION: Although no allelic or genotypic variances of this gene were observed, the possibility that SNPs within DLG4 represent a positive schizophrenia risk gene cannot be excluded. Our research provided a reference for further research into this gene in other populations.

Association between a COMT polymorphism and clinical response to risperidone treatment: a pharmacogenetic study.

A total of 130 Chinese schizophrenic patients (45 male, 85 female) were enrolled in the study. Clinical efficacy was determined using Brief Psychiatric Rating Scale (BPRS) scores. We genotyped 10 single-nucleotide polymorphisms (SNPs) of the catechol-O-methyl transferase gene (COMT) in our patients and re-examined them for association with changes in BPRS scores after 8 weeks of risperidone monotherapy. COMT is one of the genes that confer susceptibility to schizophrenia, both because of its role in neurotransmitter metabolism and because of its location in the high-risk schizophrenia-related region 22q11. Recent studies also found that COMT functional polymorphisms influenced individual response to antipsychotic medication. Our aim in this study was to explore the influence of COMT polymorphisms on pharmacological response to risperidone in the Chinese population. Statistical analysis revealed a significant association between an upstream COMT SNP, rs9606186, and scores reduction of BPRS in all patients and in the male subgroup but not in the female subgroup (allele analysis: P=0.055 for all, P=0.012 for male patients; genotype analysis: P=0.046 for all, P=0.020 for male patients, uncorrected, odds ratio=3.95). The COMT gene polymorphism, SNP rs9606186, is associated with risperidone therapy efficiency in the Chinese population. This association exhibited a sexually dimorphic difference, which may shed light on the genetics of COMT and its enzymatic sex-dependent mechanism.

No association between the USP7 gene polymorphisms and colorectal cancer in the Chinese Han population.

Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.

No association between EGR gene family polymorphisms and schizophrenia in the Chinese population.

Early growth response (EGR) genes are thought to have a role in the pathogenesis of schizophrenia because of their conserved DNA binding domain and biologically activity in neuronal plasticity. This zinc-finger motif could influence gene post-translational modification and expression. The multigenetic association model, using markers in genes of similar or antagonistic biological effects within a signal pathway or gene family, might be more appropriate to this aspect of the schizophrenia hypothesis than the single gene strategy. In this study we investigated the role of EGR1, EGR2, EGR3 and EGR4 within the EGR family. Taqman technology was used to examine 12 single nucleotide polymorphisms (SNPs) covering these four genes in 2044 Chinese Han subjects. Case-control analyses were performed to detect association of these 4 genes with schizophrenia and multifactor dimensionality reduction (MDR) analysis was employed to examine their potential gene-gene interaction in schizophrenia. Neither allelic nor genotypic single-locus tests revealed any significant association between EGR1-4 and the risk of schizophrenia nor was any such association found with regard to interaction within EGR1-4 (p(min)=0.623, CV Consistency=10/10). We concluded that although multiple candidate genes are involved in schizophrenogenic development, the EGR family may not play a major role in schizophrenia susceptibility in the Chinese Han population.

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.