3D printing flexible zinc-ion microbatteries with ultrahigh areal capacity and energy density for wearable electronics.

A flexible zinc ion micro-battery with ultra-high surface capacity (10.1 mA h cm-2) and energy density (8.1 mW h cm-2), as well as good flexibility, is fabricated based on the co-doping effect of V2O5 through an improved 3D printing technology, and is further integrated with flexible solar cells for self-powered wearable electronics.

Screening of differentially expressed proteins in psoriasis vulgaris by two-dimensional gel electrophoresis and mass spectrometry.

The aim of the present study was to elucidate differentially expressed proteins in lesional tissues of psoriasis vulgaris (PV) and normal tissues. Lesional skin tissues were collected from PV patients, along with normal skin tissues from healthy individuals. The protein content of the samples was extracted and then separated by two-dimensional gel electrophoresis (2-DGE). Any proteins that were differentially expressed in the lesional skin of PV patients compared with the healthy controls were analyzed by mass spectrometry and bioinformatics. In the stratum corneum and dermis of PV patients, the total number of proteins identified by 2-DGE was 1,969±21 and 1,928±49, respectively. Of these, 30 proteins were differentially expressed in the PV patients, of which 14 were identified as: Type 1 keratin cytoskeleton proteins (including K1C10, K1C14, K1C15 and K1C16); the type 2 keratin cytoskeleton protein, K2C1; actin-associated proteins (including ARP3, ACTA and ACTBM); prohibitin; heat shock proteins (HSPB1 and CH60); centrosome protein, CP135; and membrane associated proteins (including ANXA4 and ANXA5). The differential expression of protein between PV lesions and normal tissue can be considered as pathological biomarker. Elucidating the abnormal regulation of these proteins can provide mechanism of the development of PV and may contribute to significant approaches for PV treatments.

Characterization and Immunomodulatory Activity of a Novel Peptide, ECFSTA, from Wheat Germ Globulin.

A novel peptide was extracted from wheat germ globulin and purified using ion-exchange chromatography, gel filtration chromatography, and semi-preparative reversed-phase high-performance liquid chromatography (RP-HPLC). The sequence of the peptide was found to be Glu-Cys-Phe-Ser-Thr-Ala (ECFSTA). Its immunomodulatory effects were evaluated, and the results showed that ECFSTA could enhance phagocytosis of RAW 264.7 cells and significantly increase their secretion of nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and reactive oxygen species (ROS). ECFSTA activated macrophages mainly through the pattern recognition receptors (PRRs) of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), and the production of ROS simultaneously stimulated macrophages to produce TNF-α. Thus, ECFSTA could be used as an immunomodulator and might be a promising component of functional foods.

Association of novel polymorphisms in TMEM39A gene with systemic lupus erythematosus in a Chinese Han population.

BACKGROUND: This study aimed to assess the association between 14 single nucleotide polymorphisms (SNPs) in six genes (IRF8, TMEM39A, IKZF3, ORMDL3, GSDMB, and ZPBP2) and systemic lupus erythematosus (SLE) in a Chinese Han population sample. METHODS: We carried out a case-control study of 415 patients with SLE and 470 healthy controls without autoimmune disease or cancer. DNA for genetic analysis was isolated from the blood of all subjects using standard phenol-chloroform method. TagSNPs were identified using genotype data from the panel (Han Chinese in Beijing) of the HapMap Project and were selected using the Haploview program. Genotyping assay was conducted using the Sequenom MassARRAY iPLEX Gold platform. The frequencies of the alleles and genotypes were calculated and analyzed. Association studies and haplotype analysis were also performed. RESULTS: The genotypic frequencies of rs12493175 and rs13062955 were significantly different between the SLE patients and the healthy controls. Compared with the common homozygous genotype, the CT and CT + TT genotypes in rs12493175 and the AC and AC + AA genotypes in rs13062955 was observed to significantly reduce the risk of SLE. The haplotype analysis of TMEM39A polymorphisms showed that the CGTA haplotype frequency was significantly low in the SLE patients. CONCLUSION: Our findings identified three novel associations in SNPs located in the TMEM39A gene associated with SLE susceptibility in a Chinese Han population.

Aberrant changes of somatostatin and neuropeptide Y in brain of a genetic rat model for epilepsy: tremor rat.

Excessive excitation or loss of inhibitory neurotransmission has been closely related to epileptic activity. Somatostatin (SST) and Neuropeptide Y (NPY) are members of endogenous neuropeptides which are recognized as important modulator of classical neurotransmitter, distributed abundantly in mammalian central nervous system. Abnormal expression of these two neuropeptides evidenced in some epileptic models highlights the relevance of SST or NPY in the pathogenesis of epilepsy. The tremor rat (TRM) is a genetic epileptic animal model which can manifest tonic convulsions without any external stimuli. The present study aimed to investigate the distribution and expression of SST and NPY in TRM brains, including hippocampus, temporal lobe cortex and cerebellum. Our RT­PCR data showed that up-regulated mRNA expression of SST and NPY was discovered in TRM hippocampus and temporal lobe cortex compared with control (Wistar) rats. The peptide levels of these neuropeptides in brain areas mentioned above were both apparently higher than that in normal Wistar rats as well. However, in cerebellums, neither SST nor NPY was significantly changed compared with control group. The immunohistochemical data showed that SST and NPY were widely present throughout CA1, CA3 and the hilus of hippocampus, the entorhinal cortex of temporal lobe cortex, as well as cerebellar Purkinje layer. In conclusion, our results discovered the aberrant changes of SST and NPY in several TRM brain regions, suggesting that the peptidergic system might be involved in TRM epileptiform activity.

[Corrigendum] Upregulated LMO1 in prostate cancer acts as a novel coactivator of the androgen receptor.

After the publication of the article, the authors decided to add the following grants in the Acknowledgements section: This study was supported by grants from the National Natural Science Foundation of China (Nos. 81302221, 90813038, 31371424, 31171360 and 81372337), and Natural Science Foundation of Liaoning Province, China (No. 2013021090). [the original article was published in the International Journal of Oncology 47: 2181-2187, 2015; DOI: 10.3892/ijo.2015.3195].

Overexpression of Aiolos in Peripheral Blood Mononuclear Cell Subsets from Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Genetic studies demonstrate that the Aiolos polymorphisms contribute to the susceptibility to autoimmune diseases. The purpose of the study was to investigate the Aiolos expression in lymphocytes and monocytes in the peripheral blood from patients with SLE and RA, and to explore the correlation between Aiolos expression in cell subsets and laboratory measurements. Peripheral blood mononuclear cells (PBMC) from 32 patients with SLE, 35 patients with RA, and 37 healthy controls were purified. Aiolos expression in PBMC subsets was examined by flow cytometry. In SLE patients, a much higher percentage of Aiolos + CD8+ T cells and Aiolos + CD14+ monocytes was found, when compared with healthy controls (p = 8.29 × 10(-5) and p = 1.01 × 10(-5), respectively). Furthermore, the percentage of CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes expressing Aiolos in RA patients was also determined and each found higher than that in healthy controls (p = 0.009, p = 4.11 × 10(-5), p = 0.001, and p = 1.11 × 10(-5), respectively). The percentage of Aiolos + CD8+ T cells was weakly correlated with ESR in SLE patients and RF in RA patients (r s = 0.37, p = 0.038; r s = 0.34, p = 0.044, respectively). On the other hand, the percentage of Aiolos + CD14+ monocytes was significantly correlated with multiple laboratory measurements, including ESR, creatinine, CRP, LDH, proteinuria, albumin, and ACCPA in patients (r s = 0.62, p < 0.001; r s = 0.65, p < 0.001; r s = 0.44, p = 0.010; r s = 0.42, p = 0.022; r s = 0.52, p = 0.013; r s = 0.34, p = 0.048, respectively). To our knowledge, it is the first study to demonstrate overexpression of Aiolos in PBMC subsets in SLE and RA patients. The results indicate that overexpression of Aiolos may contribute to pathogenesis of SLE and RA.

Upregulated LMO1 in prostate cancer acts as a novel coactivator of the androgen receptor.

LMO1, a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the role of LMO1 in human prostate cancer (PCa) is still unknown. Androgen receptor (AR) plays a critical role in the progression of prostate cancer. The activation of AR signaling pathway could be modulated by AR cofactors. In the present study, we discovered that LMO1 could bind to AR and co-localize with AR in the nucleus. In addition, the expression of LMO1 in human PCa tissues was significantly higher than that in benign prostate hyperplasia (BPH) tissues. Moreover, LMO1 appeared to be a novel coactivator to enhance AR transcriptional activities, followed by the elevation of expression of P21 and PSA, downstream targets of AR. Taken together, LMO1 appears to be a coactivator of AR involved in the progression of prostate cancer, and could be a promising molecular target for treating prostate cancer.

Expression and Polymorphisms of Lysosome-Associated Protein Transmembrane 5 (LAPTM5) in Patients with Systemic Lupus Erythematosus in a Chinese Population.

Lysosome-associated protein transmembrane 5 (LAPTM5) have been demonstrated a role in the prevention of lymphocyte hyperactivation, and its deficiency is involved in the immunological dysfunction of mouse models. The aim of this study was to detect mRNA expression of LAPTM5 in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE), and to assess association between LAPTM5 single nucleotide polymorphisms (SNPs) (rs10798801, rs4614309, rs1188348, and rs1188349) and SLE in a Chinese population. Real-time transcription-polymerase chain reaction analysis was used to determine expression of LAPTM5 mRNA in PBMCs from 132 patients with SLE and 62 healthy controls. LAPTM5 mRNA expression decreased in SLE patients (n = 71) compared with healthy controls (n = 58) (p = 3.68 × 10(-5)). The expression of LAPTM5 mRNA in SLE patients with lupus nephritis (LN) (n = 35) was lower than in those without LN (n = 36) (p = 0.004). The expression level of LAPTM5 correlated with serum total protein (r(s) = 0.41, p = 0.027) and negatively correlated with 24-h proteinuria (r(s) = -0.45, p = 0.027). LAPTM5 SNPs (rs10798801, rs4614309, rs1188348, and rs1188349) was also analyzed by restriction fragment length polymorphism (RFLP) in 380 SLE patients and 460 healthy controls. No significant difference in the genotype or allele frequencies for LAPTM5 SNPs was detected in 380 SLE patients and 460 healthy controls (p > 0.05). Substantially low frequency of GGAT haplotype was observed in SLE patients (p < 0.001). It is concluded that insufficient expression of LAPTM5 may take part in the pathogenesis of SLE and contribute to the severity of the disease, and none of LAPTM5 polymorphisms contributes significantly to SLE susceptibility in a Chinese population.

PAK1-mediated MORC2 phosphorylation promotes gastric tumorigenesis.

To date, microrchidia (MORC) family CW-type zinc-finger 2 (MORC2), has been found to be involved in p21-activated kinase1 (PAK1) pathway to maintain genomic integrity. Here, we explore its novel role in cancer. We demonstrate that PAK1-mediated MORC2 phosphorylation promotes cell cycle progression, defective phosphorylation of MORC2-S677A results in attenuated cell proliferation and tumorigenicity of gastric cancer cells, which is significantly enhanced in overexpression of phospho-mimic MORC2-S677E form, suggesting the importance of MORC2 phosphorylation in tumorigenesis. More importantly, phosphorylation of MORC2 correlates positively with PAK1 expression in clinical gastric cancer. Furthermore, high expression of PAK1 and phosphorylation of MORC2 appear to be associated with poor prognosis of clinical gastric cancer. Collectively, these findings revealed a novel function of MORC2 phosphorylation in promoting gastric cell proliferation in vitro and tumorigenesis in vivo, suggesting that blocking PAK1-mediated MORC2 phosphorylation might be a potential therapeutic strategy for gastric tumorigenesis.

Association between polymorphisms of the IKZF3 gene and systemic lupus erythematosus in a Chinese Han population.

OBJECTIVE: It has been reported that IKAROS family of zinc finger 3 (IKZF3)-deficient mice spontaneously develop human systemic lupus erythematosus (SLE)-like phenotypes and produce anti-dsDNA Ab leading to immune complex-mediated glomerulonephritis. Polymorphism of the IKZF3 gene corresponds with the susceptibility to several immune-related diseases. Our intention was to establish an association between polymorphisms in the IKZF3 gene and SLE in the Chinese Han population. METHODS: The study involved obtaining blood samples for DNA extraction and genotyping the 4 selected single-nucleotide polymorphisms (SNPs) in IKZF3, including rs12150079, rs9909593, rs907091, and rs2872507, by performing PCR restriction fragment length polymorphism analysis (PCR-RFLP). A group of 366 SLE patients were compared to 455 healthy controls. RESULTS: A significant decrease in frequencies of the rs907091 CC genotype and C allele appeared in the SLE patients unlike that observed in the controls (p = 0.001 and 0.015, respectively). The frequencies of the rs12150079 genotype and allele were different between the SLE patients and the control individuals, although the significance was only marginal (p = 0.046 and 0.049, respectively). In addition, a significantly low frequency of the GGCG haplotype was observed in the SLE patients, suggesting that it may provide protection against SLE (p = 0.011). CONCLUSION: To the best of our knowledge, this is the first study to demonstrate an important association between polymorphisms in IKZF3 and SLE in the Chinese Han population. A strong association between rs907091 in the IKZF3 gene and SLE was identified.

Altered expression of neuropeptide Y, Y1 and Y2 receptors, but not Y5 receptor, within hippocampus and temporal lobe cortex of tremor rats.

As an endogenous inhibitor of glutamate-mediated synaptic transmission in mammalian central nervous system, neuropeptide Y (NPY) plays a crucial role in regulating homeostasis of neuron excitability. Loss of balance between excitatory and inhibitory neurotransmission is thought to be a chief mechanism of epileptogenesis. The abnormal expression of NPY and its receptors observed following seizures have been demonstrated to be related to the production of epilepsy. The tremor rat (TRM) is a hereditary epileptic animal model. So far, there is no report concerning whether NPY and its receptors may be involved in TRM pathogenesis. In this study, we focused on the expression of NPY and its three receptor subtypes: Y1R, Y2R and Y5R in the TRM brain. We first found the expression of NPY in TRM hippocampus and temporal lobe cortex was increased compared with control (Wistar) rats. The mRNA and protein expression of Y1R was down-regulated in hippocampus but up-regulated in temporal lobe cortex, whereas Y2R expression was significantly increased in both areas. There was no significant change of Y5R expression in either area. The immunohistochemistry data showed that Y1R, Y2R, Y5R were present throughout CA1, CA3, dentate gyrus (DG) and the entorhinal cortex which is included in the temporal lobe cortex of TRM. In conclusion, our results showed the altered expression of NPY, Y1R and Y2R but not Y5R in hippocampus and temporal lobe cortex of TRM brain. This abnormal expression may be associated with the generation of epileptiform activity and provide a candidate target for treatment of genetic epilepsy.

Proteomics identifies differentially expressed proteins in neonatal murine thymus compared with adults.

BACKGROUND: The thymus is an immune organ essential for life and plays a crucial role in the development of T cells. It undergoes a fetal to adult developmental maturation process occurring in mouse during the postnatal months. The molecular modifications underlying these ontogenic changes are essentially unknown. Here we used a differential proteomic-based technique (2D-Difference Gel Electrophoresis) coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to search for key proteins in the postnatal development of the thymus. Eight different BALB/c mice were used in the study: four mice aged of 1 day (neonatal) and four mice aged of 60 days (adult). Protein samples derived from thymus were labeled and run in 2D-PAGE (Two-Dimensional Polyacrylamide Gel Electrophoresis). One whole-thymus tissue from each mouse was run on gels and each gel containing a pooled sample of the eight mice was run in parallel. The pooled sample was set as the internal pool, containing equal amount of each protein extract used in the experiment. Gels were matched and compared with Difference In-gel Analysis software. Differential spots were picked, in-gel digested and peptide mass fingerprints were obtained. RESULTS: Among the differentially regulated proteins in neonatal thymus group, 111 proteins were identified by mass spectrometry, of which 95 proteins were up-regulated and 16 proteins were down-regulated. The identified proteins belong to several functional categories, including cell proliferation, cycle and apoptosis, transcription regulation, signal transduction, nucleotide processing, proteolysis and translation, protein folding, metabolism, oxidoreduction, cytoskeleton, immune response, and embryonic development. The major interaction networks comprised of cellular function and maintenance, cellular assembly and organization, and metabolism were also identified by STRING analysis. CONCLUSIONS: The demonstrated molecular changes are relevant for understanding thymus development as well as neonatal immune function, and they provide the diagnostic disease markers. Further studies will be required to describe in detail the role of the identified proteins in thymus maturation and in the specific functions of neonatal thymus.

Identification and expression analysis of a novel CW-type zinc finger protein MORC2 in cancer cells.

Microrchidia2 (MORC2) is a member of the MORC protein family that is localized to both the nucleus and cytoplasm when transiently expressed in gastric cancer cells. We identified and analyzed the functional domains of MORC2, which has specific unique structural characteristics compared to the other MORC proteins. Our data showed that nuclear localization signals (NLS) of MORC2 was mainly dependent on the NLS amino acids (aa) 657-781 and cytoplasmic localization of MORC2 was attributed to the nuclear export signal (NES) aa 481-657. Moreover, the NLS appears to predominate over the NES in the localization of full-length human MORC2 indicating that MORC2 is localized mainly in the nucleus. Our results also demonstrated that the NLS (aa 657-781) and proline-rich domain within MORC2 C-terminus were required for the transcriptional repressive role in cancer cells.

Downregulation of p21-activated kinase-1 inhibits the growth of gastric cancer cells involving cyclin B1.

p21-Activated kinase 1 (Pak1), a serine/threonine kinase, has been implicated in cytoskeletal remodelling, cell motility, apoptosis and transformation. However, the role of Pak1 in gastric cancer remains unclear. In this study, we detected Pak1 expression in gastric cancer tissues from 40 patients by western blot. Overexpression of Pak1 was associated with progression, metastasis and prognosis of gastric cancer. In addition, we found that knockdown of Pak1 expression significantly inhibited anchorage-dependent and anchorage-independent growth in gastric cancer cells, and markedly inhibited gastric cancer cell xenograft tumor growth. In further study, data showed that Pak1 could regulate the expression of cyclin B1 at the mRNA and protein levels, and impact the subcellular distribution and the promoter activity of cyclin B1. Results from deletion and mutant analysis supplied a new NF-kappaB binding sites at position -321 of cyclin B1 promoter, and indicated that Pak1 regulated the transcription of cyclin B1 in gastric cancer through NF-kappaB. In conclusion, Pak1 may be a potential prognostic marker and therapeutic target in gastric cancer.

Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression.

Curcumin (diferuloylmethane), is a natural chemopreventive agent known to inhibit the proliferation of several cancer cell lines. It has been previously demonstrated that curcumin is a potent inhibitor of EGF-receptor (EGFR) tyrosine kinase, but its inhibitive effect on p21-activated kinase 1 (PAK1), a downstream protein of EGFR, has not been defined. In this paper we found that curcumin repressed the expression of HER2 and inhibited the kinase activity of PAK1 without affecting its expression. Silencing HER2 in gastric cancer cells showed that even if PAK1 activity was transiently strengthened by EGF, curcumin still had a strong inhibitive effect. It should be emphasized that kinase assay in vitro showed that curcumin could act as an ATP-competitive inhibitor, which was supported by computer-aided molecular modeling. Curcumin also downregulated the mRNA and the protein expression of cyclin D1 and suppressed transition of the cells from G(1) to S phase. Therefore, curcumin inhibited the proliferation and invasion of gastric cancer cells. Overall, these results provided novel insights into the mechanisms of curcumin inhibition of gastric cancer cell growth and potential therapeutic strategies for gastric cancer.