Search

DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene. A luciferase assay performed with several truncated constructs identified a 501‐bp region as the core promoter region of DHX15. Site‐directed mutagenesis, electrophoretic mobility shift and chromatin immunoprecipitation assays showed that ETS1 and SP1 occupied the DHX15 promoter. Furthermore, knockdown of ETS1 and SP1 resulted in suppression of DHX15, whereas the overexpression of these genes led to up‐regulation of DHX15. Interestingly, in samples obtained from patients with ALL at diagnosis, both ETS1 and SP1 correlated positively with DHX15 expression. Additionally, differences in methylation of the DHX15 core promoter region were not observed between the patients and controls. In conclusion, we identified the core promoter region of DHX15 and demonstrated that ETS1 and SP1 regulated DHX15 expression in ALL.

Background Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. Objective The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia. Methods We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel. Sanger sequencing, segregation analysis, and phenotypic reevaluation were used to substantiate the findings. Results The clinical characteristics of the enrolled 163 probands were summarized. A total of 39 heterozygous variants were identified, of which 33 were classified as benign, likely benign, and uncertain significance. The remaining 6 variants (3 novel, 3 documented) were pathogenic and likely pathogenic. Of these, 3 were de novo (potassium calcium-activated channel subfamily M alpha 1, c.1534A>G; solute carrier family 2 member 1, c.418G>A; sodium voltage-gated channel alpha subunit 8, c.3640G>A) in 3 sporadic individuals, respectively. The other 3 (paroxysmal nonkinesiogenic dyskinesia protein, c.956dupA; potassium voltage-gated channel subfamily A member 1, c.765C>A; Dishevelled, Egl-10, and Pleckstrin domain containing 5, c.3311C>T) cosegregated in 3 families. All 6 cases presented with typical paroxysmal kinesigenic dyskinesia characteristics, except for the Dishevelled, Egl-10, and Pleckstrin domain containing 5 family, where the proband's mother had abnormal discharges in her temporal lobes in addition to paroxysmal kinesigenic dyskinesia episodes. Conclusions Our findings extend the genotypic spectrum of paroxysmal kinesigenic dyskinesia and establish the associations between paroxysmal kinesigenic dyskinesia and genes classically related to other paroxysmal movement disorders. De novo variants might be a cause of sporadic paroxysmal kinesigenic dyskinesia. © 2018 International Parkinson and Movement Disorder Society.

The metallic nanostructures with unique properties of tunable plasmon resonance and large field enhancement have been cooperated with semiconductor to construct hetero-nanostructures for various applications. Herein, a general and facile approach to synthesize uniform dumbbell-like gold–sulfide core–shell hetero-nanostructures is reported. The transformation from Au nanorods (NRs) to dumbbell-like Au NRs and coating of metal sulfide shells (including Bi2S3, CdS, CuxS, and ZnS) are achieved in a one-pot reaction. Due to the reshaping of Au core and the deposition of sulfide shell, the plasmon resonances of Au NRs are highly enhanced, especially the about 2 times enhancement for the visible transverse plasmon resonance compared with the initial Au NRs. Owing to the highly enhanced visible light absorption and strong local electric field, we find the photocatalytic activity of dumbbell-like Au–Bi2S3 NRs is largely enhanced compared with pure Bi2S3 and normal Au–Bi2S3 NRs by testing the photodegradation rate of Rhodamine B (RhB). Moreover, the second-layer sulfide can be coated and the double-shell Au–Bi2S3–CdS hetero-nanostructures show further improved photodegradation rate, especially about 2 times than that of Degussa P25 TiO2 (P25) ascribing to the optimum band arrangement and then the prolonged lifetime of photo-generated carriers.

A two-step chemical approach to synthesize high quality Fe3O4 nanodisc is reported. The magnetic hyperthermia properties of the nanodisc and isotropic nanoparticles are investigated systematically. The results suggest that the nanodisc shows much higher specific absorption rate (SAR) than isotropic nanoparticles. This is attributed to the parallel alignment of nanodisc with respect to the alternating current magnetic field, which is confirmed by good agreement between experimental results and micromagnetic simulation. It is found that such parallel alignment could enhance the SAR value by a factor of approximate to 2 with respect to the randomly oriented case. The above results indicate that the nanodisc provides an excellent thermal seed for magnetic hyperthermia. This study sheds the light on the magnetic hyperthermia mechanism of magnetic nanodisc and it also opens the window to explore high efficiency thermal seeds by controlling the orientation of magnetic nanostructures.

Metal/semiconductor Au/Ag2S core/shell hetero-nanorods with controlled morphology are synthesized and their tunable plasmon enhancements (involving linear and nonlinear optical processes) are demonstrated. The synthesis involves site-selective deposition of Ag layer onto Au nanorod seeds, followed by site-selective sulfuration of the Ag layer, resulting in three types of Au/Ag2S core/shell nanorods with complete, corner-opened, or end-opened shells. The plasmon resonance and local field confinements varing with shell morphology are analyzed using FDTD calculations. Nonlinear measurements reveal that the Ag2S shell with appropriate morphology leads to the nonlinear refraction and saturable intensity of the Au nanorods increasing 7.6 and 4.1 times, respectively, which indicates strong plasmon enhancements and energy relaxation in the Au/Ag2S core/shell nanorods. This site-selective shell growth strategy offers a constructive bottom-up approach to maneuver the optical properties of plasmonic nanocrystals for various applications.

The recent emergence of numerous nanotechnologies is expected to facilitate the development of regenerative medicine, which is a tissue regeneration technique based on the replacement/repair of diseased tissue or organs to restore the function of lost, damaged, and aging cells in the human body. In particular, the unique magnetic properties and specific dimensions of magnetic nanomaterials make them promising innovative components capable of significantly advancing the field of tissue regeneration. Their potential applications in tissue regeneration are the focus here, beginning with the fundamentals of magnetic nanomaterials. How nanomaterials-both those that are intrinsically magnetic and those that respond to an externally applied magnetic field-can enhance the efficiency of tissue regeneration is also described. Applications including magnetically controlled cargo delivery and release, real-time visualization and tracking of transplanted cells, magnetic regulation of cell proliferation/differentiation, and magnetic activation of targeted ion channels and signal pathways involved in regeneration are highlighted, and comments on the perspectives and challenges in magnetic nanomaterial-based tissue regeneration are given.

Background Lung cancer is one of the higher incidences of malignant tumors around the world. At present, tumor markers CEA, CA19-9, and CA-125 in serum are used for the diagnosis of lung cancer, however, fewer studies have shown tumor markers for early diagnosis. Therefore, using quantitative mass spectrometry, differential mitochondrial proteome analysis was performed, comparing human lung adenocarcinoma and normal bronchial epithelium cells. Methods A human lung adenocarcinoma cell line A549 and a normal human bronchial epithelial cell line 16HBE were cultured in vitro. The cell mitochondria of the two cell lines were extracted and purified by differential centrifugation and percoll density gradient centrifugation. The integrity and purity of mitochondria were validated by electron microscopy and Western-blot. The proteins/peptides from lung cancer cells and normal cells were marked by the same amount of relative and absolute quantification of ectopic tags (iTRAQ). The mixed samples were analyzed and identified by two-dimensional liquid chromatography – tandem mass spectrometry (2D-LC-MS/MS). The proteome was analyzed with different bioinformatic tools. Results One hundred and sixty-one mitochondrial proteins were identified. One hundred and fifty-three mitochondrial proteins, which were expressed differently between 16HBE cells and A549 cells, were identified. Sixty-seven proteins were high expression, while 86 proteins were lower expression. Expression of three proteins: ornithine aminotransferase (OAT), heat shock protein beta90 (HSP90), and vimentin (VIM), was increased more than twice. Our results, in combination with the literature review, suggest that HSP90 and Vimentin may be the new tumor markers of lung cancer.

A simple, specific and reproducible liquid chromatography–electrospray ionization mass spectrometry was developed and validated for the determination of jolkinolide B, a potential antitumor active component isolated from Euphorbia fischeriana, in rat plasma. Chromatographic separation was achieved on a Venusil MP-C18 column using an isocratic elution. Jolkinolide B and osthole (internal standard) were monitored by positive electrospray ionization in the selected reaction monitoring mode. Good linearity (r2 > 0.996) was achieved by a weighted (1/x2) linear least-squares regression over a concentration range of 6.50–2600 ng/mL. The accuracy and precision of the assay were satisfactory and the method proved to be applicable to pharmacokinetics following a single intravenous bolus injection of jolkinolide B to rats. Copyright © 2013 John Wiley & Sons, Ltd.

Isolation and structure-determination of ginsenoside Rh10 (I) and notoginsenoside ST-6 (II) are presented.

Xu J D, Furuya T, Cao X X, Liu X L, Li Q Q, Wang W J, Xu J W, Xu Z D, Sasaki K & Liu X P (2010) Histopathology57, 814–824 Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma Aims: BCL2L10 protein is an apoptosis-related member of the Bcl-2 protein family. The clinical significance of its expression in gastric carcinoma is poorly understood. The aim was to investigate BCL2L10 expression and its clinical and prognostic significance in gastric carcinoma patients. Methods and results: Immunohistochemistry, real–time polymerase chain reaction (PCR) and immunoblotting all revealed extensive loss of BCL2L10 expression in gastric cancer cells. The scaled BCL2L10 expression data was categorized into three groups (groups 0–2) to facilitate statistical analysis. A significant correlation was observed between the lower BCL2L10 expression group and shorter disease-free survival (P = 1.956 × 10−18). Multivariate regression analysis showed that loss of BCL2L10 protein expression [P = 4.883 × 10−8, hazard ratio (HR) = 0.252] is an independent prognostic predictor of gastric carcinoma. The receiver operator characteristic (ROC) curve showed that the area for BCL2L10 protein was 0.817 (P = 8.331 × 10−14), indicating that loss of BCL2L10 protein expression is an excellent prognostic predictor of gastric carcinoma. Conclusions: Loss of BCL2L10 protein expression predicts poor clinical outcome in gastric carcinoma.

The reason for and consequences of BCL2L10 down-regulation in gastric carcinoma are poorly understood. Our aim was to investigate the function of the protein BCL2L10 in gastric carcinoma. We investigated BCL2L10 expression using quantitative real-time PCR and immunoblotting. The methylation status of the BCL2L10 gene promoter was examined by bisulphite sequencing in fresh gastric normal and carcinoma tissues. We studied apoptosis and proliferation regulation in gastric cancer cell lines using flow cytometry, fluorescence staining, murine xenografting and immunoblotting. Pathway inhibitors were applied to confirm the major pathways involved in apoptosis or proliferation regulation. We observed significant correlations between lower BCL2L10 expression and CpG island hypermethylation of the BCL2L10 gene promoter in gastric carcinoma, apoptosis induced by over-expressed BCL2L10 through mitochondrial pathways, and proliferation accelerated by BCL2L10 siRNA via the PI3K-Akt signalling pathway in gastric cancer cell lines. The pro-apoptotic effect of BCL2L10 and growth promotion by BCL2L10 siRNA in gastric cancer cells suggest that it may be a tumour suppressor.

Objective: To investigate the expression and the clinical significance of basic fibroblast growth factor (b-FGF) and endostatin in osteosarcoma. Methods: From January 2003 to December 2005, expression of b-FGF, endostatin and CD34 were detected in 30 osteosarcoma and 30 osteochondroma tissue specimens by the immunohistochemical Elivision method. All data were post-processed with SPSS 13.0 software and prepared for investigation and analysis of these expressions and the relationships between the parameters. Results: (i) The rates of expression of b-FGF, endostatin and CD34 protein in osteosarcoma were 76.7%, 93.3%, and 96.7%, respectively, and in osteochondroma 43.3%, 40.0% and 16.7%, respectively. Each of the three expressions showed obvious differences between the osteosarcoma and the osteochondroma group. (ii) In the osteosarcoma group, expression of endostatin was positively correlated with that of CD34 (P < 0.05, γs = 0.528), and expression of endostatin in poorly differentiated osteosarcoma was much greater than that in highly differentiated osteosarcoma (P= 0.004). Expression of endostatin correlated with osteosarcoma metastasis (P= 0.036). (iii) There was no correlation between b-FGF and endostatin expression rates (P= 0.182) in the osteosarcoma group. Conclusion: Angiogenesis is the basis of tumor metastasis, as well as being an important factor in tumor growth. Expression of endostatin could be adopted as a parameter for the diagnosis of postoperative metastases and for assessing prognosis, and could act as an adjuvant indicator in the grading of osteosarcoma.

We aimed to investigate the expression of RACK1 in breast cancer, evaluate its role in predicting prognosis and compare with commonly used biomarkers: Ki67, ER, PR and HER-2 for patients with breast cancer. The RACK1 expression and its clinical significance were examined in 160 breast carcinoma patients using immunohistochemistry. Correlations of RACK1 expression with other commonly used biomarkers and survival analyses were assessed. Immunohistochemistry results showed that the number of RACK1 cases scoring 0, 1, and 2 were 66, 54, and 40, respectively. RACK1 staining was strongly related to clinical stage, histological grade, Ki67, ER, PR and HER-2 (all p < 0.05). Consistently, all of the cases exhibiting RACK1 staining score 0 were survivors, whereas the majority (55.0%) of those exhibiting RACK1 staining score 2 were deaths. Kaplan-Meier survival analysis of 160 cases revealed a correlation between higher RACK1 expression levels and shorter overall survival times (p < 0.001). Univariate and multivariate analyses revealed that RACK1, tumor size, lymph node metastasis, and HER-2 were independent prognostic factors (all p < 0.05). Interestingly, receiver operator characteristic (ROC) curves showed that the ROC areas for RACK1, Ki67, ER, PR and HER-2 were 0.833, 0.766, 0.446, 0.387, and 0.689, respectively, and the superiority of RACK1 in sensitivity and specificity as biomarker was demonstrated. To our knowledge, it is the first time to investigate the expression of RACK1, and identified that RACK1 is a superior independent biomarker for diagnosis and prognosis comparing with currently widely used diagnostic index in breast carcinoma.

Hydrophobic association hydrogels (HA-gels) with almost ideal properties were successfully prepared by micellar copolymerization, and the associated micelles acted as physical cross-linking points in the network of HA-gels. HA-gels exhibit exceptional mechanical properties and transparency. However, the most striking properties are that HA-gels possess the capability of self-healing and remolding, which is mainly due to the dissociation and re-association process of the associated micelles. Dried-gels, which were prepared by stretching HA-gels to a certain elongation for a period of time in the air, can be used as shrinkable or thermal sensitivity materials. HA-gels have a broad selectivity for components, so we have synthesized HA-gels with variously available properties by changing a corresponding component: thermoresponsive HA-gels, nanosphere-composite HA-gels, and fluorescent HA-gels. Therefore, we are sure that HA-gels will be widely used in various fields, such as biology, medication, sensors, optics, and oil exploitation.

Nephrin is a signalling cell-cell adhesion protein of the Ig superfamily and the first identified component of the slit diaphragm that forms the critical and ultimate part of the glomerular ultrafiltration barrier. The extracellular domains of the nephrin molecules form a network of homophilic and heterophilic interactions building the structural scaffold of the slit diaphragm between the podocyte foot processes. The intracellular domain of nephrin is connected indirectly to the actin cytoskeleton, is tyrosine phosphorylated, and mediates signalling from the slit diaphragm into the podocytes. CD2AP, podocin, Fyn kinase, and phosphoinositide 3-kinase are reported intracellular interacting partners of nephrin, although the biological roles of these interactions are unclarified. To characterize the structural properties and protein-protein interactions of the nephrin intracellular domain, we produced a series of recombinant nephrin proteins. These were able to bind all previously identified ligands, although the interaction with CD2AP appeared to be of extremely low stoichiometry. Fyn phosphorylated nephrin proteins efficiently in vitro. This phosphorylation was required for the binding of phosphoinositide 3-kinase, and significantly enhanced binding of Fyn itself. A protein of 190 kDa was found to associate with the immobilized glutathione S-transferase-nephrin. Peptide mass fingerprinting and amino acid sequencing identified this protein as IQGAP1, an effector protein of small GTPases Rac1 and Cdc42 and a putative regulator of cell-cell adherens junctions. IQGAP1 is expressed in podocytes at significant levels, and could be found at the immediate vicinity of the slit diaphragm. However, further studies are needed to confirm the biological significance of this interaction and its occurrence in vivo.