Genetic factors related to the regulation of apoptosis in schizophrenia patients may be involved in a reduced vulnerability to cancer. XRCC4 is one of the potential candidate genes associated with schizophrenia which might induce colorectal cancer resistance.

Cardiac hypertrophy in response to multiple stimuli has important physiological and pathological significances. GATA4 serves as a nuclear integrator of several signalling pathways during cardiac hypertrophy. Sp1 and Sp3 are also reported to be involved in this process. However, the mechanism by which GATA4 acts as a mediator, integrating these ubiquitously expressed transcriptional factors, is poorly understood. We found that the expression of GATA4 and Sp1 was up-regulated in the myocardium of a pressure overload hypertrophy rat model, as well in phenylephrine-induced (PE-induced) hypertrophic growth of neonatal cardiomyocytes. GST pull-down assays demonstrated that GATA4 could interact with Sp1 in vitro. Therefore, we proposed that GATA4 cooperates with Sp1 in regulating ANF expression, as its reactivation is closely linked with hypertrophy. Further studies demonstrated that GATA4 could activate the ANF promoter synergistically with Sp1 through direct interaction. In contrast, Sp3 exhibited antagonistic function, and overexpression of Sp3 repressed the transcriptional synergy between Sp1 and GATA4. We also found that Sp1 alone could activate the ANF promoter in cardiomyocytes, whereas Sp3 exerted negative effects on ANF expression. Bioinformatics analysis revealed novel Sp-binding sites on the ANF promoter. The recruitment of GATA4 and Sp1 on the ANF promoter was enhanced during phenylephrine-mediated hypertrophy, whereas the recruitment of Sp3 was reduced. The phosphorylation of GATA4 by ERK1/2 kinase could enhance the affinity between GATA4 and Sp1. Thus, our findings revealed the critical interaction of GATA4 and Sp1 in modulating ANF expression, indicating their involvement in cardiac hypertrophy.

We carried out an association study between GNB1L and three mental disorders (major depressive disorder, bipolar disorder, schizophrenia) in Chinese Han population. Among 1135 cases and 1135 controls, findings suggests that GNB1L is linked with bipolar disorder and schizophrenia and not with major depressive disorder.

MicroRNAs are key regulators of many biological processes, including cell differentiation. Here we show that during human monocyte-macrophage differentiation, expression of the microRNAs miR-223, miR-15a and miR-16 decreased considerably, which led to higher expression of the serine-threonine kinase IKKalpha in macrophages. In macrophages, higher IKKalpha expression in conjunction with stabilization of the kinase NIK induced larger amounts of p52. Because of low expression of the transcription factor RelB in untreated macrophages, high p52 expression repressed basal transcription of both canonical and noncanonical NF-kappaB target genes. However, proinflammatory stimuli in macrophages resulted in greater induction of noncanonical NF-kappaB target genes. Thus, a decrease in certain microRNAs probably prevents macrophage hyperactivation yet primes the macrophage for certain responses to proinflammatory stimuli.

A contusive model of spinal cord injury at spinal segment T8-9 was established in rats. Huantiao (GB30) and Huatuojiaji (Ex-B05) were punctured with needles, and endogenous neural stem cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) and NG2. Double immunofluorescence staining showed that electroacupuncture markedly increased the numbers of BrdU(+)/NG2(+) cells at spinal cord tissue 15 mm away from the injury center in the rostral and caudal directions. The results suggest that electroacupuncture promotes the proliferation of endogenous neural stem cells and oligodendrocytes in rats with spinal cord injury.

TMPRSS4 (Transmembrane protease serine 4) is up-regulated in a broad spectrum of cancers. However, little is known about the biological effects of TMPRSS4 on hepatocellular carcinoma (HCC) and the related mechanisms. In the present study, we found that overexpression of TMPRSS4 significantly promoted the invasion, migration, adhesion and metastasis of HCC. Further more, TMPRSS4 induced EMT of HCC, which was mediated via snail and slug as a result of Raf/MEK/ERK1/2 activation, and inhibition of ERK1/2 activation by its inhibitor was associated with reduced cell invasion and reversion of EMT. In addition, we demonstrated that TMPRSS4 remarkably suppressed the expression of RECK, an inhibitor of angiogenesis, and drastically induced tumor angiogenesis and growth. More important, in clinical HCC specimens, TMPRSS4 expression was significantly correlated with tumor staging and was inversely correlated with E-cadherin and RECKS expression. Expression of TMPRSS4 is significantly associated with HCC progression and is an independent prognostic factor for postoperative worse survival and recurrence. In conclusion, TMPRSS4 functions as a positive regulator of Raf/MEK/ERK1/2 pathway and promotes HCC progression by inducing EMT and angiogenesis. The increase of TMPRSS4 expression may be a key event for HCC progression and may be regarded as a potential prognostic marker for HCC.

Wear debris of polyethylene has become a restraining factor of the durability for total hip arthroplasty (THA). Ceramic on ceramic (COC) has better wear resistance while the squeaking sound and prosthesis fracture are of concern. It is still a controversy that bearing couples are better for THA.

Microglia/macrophages (MG/MΦ) are found in the subretinal space in both mice and humans. Our goal was to study the spatial and temporal distribution, the phenotype, and gene expression of subretinal MG/MΦ in mice with normal retinas and compare them to mice with known retinal pathology.

Our previous studies demonstrated that the topical application of caffeine is a potent inhibitor of UVB-induced carcinogenesis and selectively increases apoptosis in tumors but not in non-tumor areas of the epidermis in mice that are at a high risk for developing skin cancer. While this effect is mainly through a p53 independent pathway, the mechanism by which caffeine inhibits skin tumor formation has not been fully elucidated. Since caffeine is a non-specific phosphodiesterase inhibitor, we investigated the effects of several PDE inhibitors on the formation of sunburn cells in mouse skin after an acute exposure to ultraviolet light B (UVB). The topical application of a PDE2 inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA hydrochloride), stimulated epidermal apoptosis compared to control (P<0.01) and to a greater extent than caffeine whereas a PDE4 inhibitor attenuated the epidermal apoptosis compared to control (P<0.01). Since PDE2 hydrolyzes cyclic nucleotides, mainly cGMP, the effects of EHNA hydrochloride on epidermal apoptosis following UVB exposure may be mediated, in part, by increased cGMP signaling. Data demonstrated that the topical application of dibutyryl cGMP stimulated epidermal apoptosis (P<0.01) following an acute exposure to UVB. Treating UVB-pretreated mice topically with 3.1 µmole or 0.8 µmole of EHNA hydrochloride attenuated tumor formation to a greater extent than treating with 6.2 µmole caffeine when these compounds were applied once a day, five days a week for 18 weeks. These observations suggest a novel role for PDE2 in UVB-induced tumorigenesis and that PDE2 inhibitors that mediate cGMP signaling may be useful for the prevention and treatment of skin cancer.

As a cleavage enzyme of precursor TNF-α, the high expression level of ADAM17 in endothelial cells is an important factor in atherosclerosis. In this study, we demonstrate that ADAM17 is the target of miR-152. We found that miR-152 could reduce TNF precursor cleavage and inhibit cell proliferation and migration by targeting ADAM17 in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression pattern of miR-152 and corresponding target ADAM17 was opposite in HUVECs under hypoxic conditions. The levels of circulating miR-152 in AS patient sera were lower than those detected in the sera of normal individuals. Our results indicate that miR-152 may be involved in the development of human atherosclerosis and could be used as diagnostic biomarker or therapeutic target in atherosclerosis.

To investigate the effect of luteolin on methamphetamine (MA)-induced behavioral sensitization and mitogen-activated protein kinase (MAPK) signal transduction pathway activation in mice.

Voltage-gated L-type calcium channels (VLCC) are distributed widely throughout the brain. Among the genes involved in schizophrenia (SCZ), genes encoding VLCC subunits have attracted widespread attention. Among the four subunits comprising the VLCC (α - 1, α -2/δ, β, and γ), the γ subunit that comprises an eight-member protein family is the least well understood. In our study, to further investigate the risk susceptibility by the γ subunit gene family to SCZ, we conducted a large-scale association study in Han Chinese individuals. The SNP rs17645023 located in the intergenic region of CACNG4 and CACNG5 was identified to be significantly associated with SCZ (OR = 0.856, P = 5.43 × 10(-5)). Similar results were obtained in the meta-analysis with the current SCZ PGC data (OR = 0.8853). We also identified a two-SNP haplotype (rs10420331-rs11084307, P = 1.4 × 10(-6)) covering the intronic region of CACNG8 to be significantly associated with SCZ. Epistasis analyses were conducted, and significant statistical interaction (OR = 0.622, P = 2.93 × 10(-6), Pperm < 0.001) was observed between rs192808 (CACNG6) and rs2048137 (CACNG5). Our results indicate that CACNG4, CACNG5, CACNG6 and CACNG8 may contribute to the risk of SCZ. The statistical epistasis identified between CACNG5 and CACNG6 suggests that there may be an underlying biological interaction between the two genes.

To assess the accuracy of transient elastography (TE) in the prediction of esophageal varices (EV).

Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field.

The 5-HT1A receptor (HTR1A) and the 5-HT5A receptor (HTR5A) are key 5-HT receptors with distinct inhibitory functions. Studies have been conducted to investigate the association of a few HTR1A polymorphisms with schizophrenia, producing conflicting results, and the relationship between HTR5A and schizophrenia has not yet been well investigated. We aimed to examine the association of HTR1A and HTR5A with schizophrenia and executive function. The study included a discovery stage with 1,115 patients and 2,289 controls and a replication stage with 2,128 patients and 3,865 controls. A total of 30 common SNPs in HTR1A and HTR5A were genotyped in the discovery stage, and significantly associated SNPs were genotyped in the replication stage. We identified that two SNPs (rs878567 in HTR1A and rs1800883 in HTR5A) were significantly associated with schizophrenia in both datasets, and similar results were observed in imputation and haplotype association analyses. Moreover, we found that SNP rs1800883 significantly interacted with executive function when processing the perseverative error of Wisconsin Card Sorting Test in patients. Our results provide further supportive evidence of the effect of HTR1A and HTR5A on the etiology of schizophrenia and suggest that the selected genetic variations in HTR5A may be involved in impaired executive function.

The prevalence of deep vein thrombosis (DVT) and its risk factors in patients with cervical spondylotic myelopathy (CSM) before spinal surgery are poorly understood. We investigated this association with a retrospective cross-sectional study.

A major limitation in the development of effective scaffolds for bone regeneration has been the limited vascularization of the regenerating tissue. Here, we propose the development of a novel calcium phosphate cement (CPC)-based scaffold combining the properties of mesoporous silica (MS) with recombinant human bone morphogenic protein-2 (rhBMP-2) to facilitate vascularization and osteogenesis. Specifically, the development of a custom MS/CPC paste allowed the three-dimensional (3D) printing of scaffolds with a defined macroporous structure and optimized silicon (Si) ions release profile to promote the ingrowth of vascular tissue at an early stage after implantation in support of tissue viability and osteogenesis. In addition, the scaffold microstructure allowed the prolonged release of rhBMP-2, which in turn significantly stimulated the osteogenesis of human bone marrow stromal cells in vitro and of bone regeneration in vivo as shown in a rabbit femur defect repair model. Thus, the combination MS/CPC/rhBMP-2 scaffolds might provide a solution to issues of tissue necrosis during the regeneration process and therefore might be able to be readily developed into a useful tool for bone repair in the clinic.

Serine proteinases have been recognized as playing an important role in inflammation via proteinase activated receptors (PARs). However, little is known about the influence of serine proteinases and PARs on TNF secretion from highly purified T cells. We challenged T cells from human peripheral blood with serine proteinases and agonist peptides of PARs and measured the levels of TNF in culture supernatants by ELISA. The results showed that thrombin and trypsin, but not tryptase, stimulated approximately up to 2.5-fold increase in TNF release from T cells following 16 h incubation. Proteinase inhibitors and PAR-1 antagonist SCH 79797 almost completely abolished thrombin- and trypsin-induced TNF release from T cells. Agonist peptides of PAR-1, but not PAR-2 induced TNF release from T cells. Moreover, trypsin- and thrombin-induced upregulated expression of TNF was observed in CD4+, IL-4+, or CD25+ T cells, but not in IFN+ or IL-17+ T cells. The signaling pathways MAPK/ERK and PI3K/Akt are involved in the thrombin- and trypsin-induced TNF release from T cells. In conclusion, thrombin and trypsin can induce TNF release from IL-4+ and CD25+ T cells through activation of PAR-1 and therefore contribute to regulation of immune response and inflammation of the body.

Abnormal growth of vertebral body growth plate (VBGP) is considered as one of the etiologic factors in the adolescent idiopathic scoliosis (AIS). It was well-known that melatonin was correlated with the emergence and development of AIS. This study aimed to investigate the effect of melatonin on rat VBGP chondrocytes in vitro.

Using magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (rsfMRI) to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD).