miR-3677-3p promotes hepatocellular carcinoma progression via inhibiting GSK3ß.

MicroRNAs play important roles in regulating hepatocellular carcinoma (HCC) formation, progression and metastasis. However, their functions and the underlying molecular mechanisms are still unclear. Here, we found that miR-3677-3p was highly expressed in primary tumor tissues of HCC patients. And its inhibition by using sponge in HCC cells could suppress cell proliferation significantly, but it has no effect on cell apoptosis. Through directly targeting to the 3' untranslated region of glycogen synthase kinase 3-ß (GSK3ß), miR-3677-3p could inhibit GSK3ß expression. Our study revealed that the miR-3677-3p/GSK3ß axis may play a crucial role in HCC and miR-3677-3p may serve as a potential diagnostic biomarker or a therapeutic target for HCC.

Expression and Prognostic Significance of p53 in Glioma Patients: A Meta-analysis.

Glioma is a brain tumor deriving from the neoplastic glial cells or neuroglia. Due to its resistance to anticancer drugs and different disease progress of individuals, patients with high-grade glioma are difficult to completely cure, leading to a poor prognosis and low overall survival. Therefore, there is an urgent need to look for prognostic and diagnostic indicators that can predict glioma grades. P53 is one of the widely studied biomarkers in human glioma. The purpose of this study was to comprehensively evaluate the significance of p53 expression in glioma grades and overall survival. We searched commonly used electronic databases to retrieve related articles of p53 expression in glioma. Overall, a total of 21 studies including 1322 glioma patients were finally screened out. We observed that the frequency of p53 immuno-positivity was higher in high-grade patients than that in low-grade category (63.8 vs. 41.6 %), and our statistic analysis indicated that p53 expression was associated with pathological grade of glioma (OR 2.93, 95 % CI 1.87-4.60, P < 0.00001). This significant correction was also found in 1-, 3- and 5-year overall survival. However, no positive relationship was found between age, sex, tumor size and p53 expression in patients with glioma. In conclusion, our results suggested that p53 immunohistochemical expression might have an effective usefulness in predicting the prognosis in patients with glioma.

Experimental confirmation of driving pressure boosting and smoothing for hybrid-drive inertial fusion at the 100-kJ laser facility.

In laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43-50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6-4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8-4.0 and 3.5-3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured.

Pyrroloquinoline quinone attenuates isoproterenol hydrochloride­induced cardiac hypertrophy in AC16 cells by inhibiting the NF­κB signaling pathway.

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox co­factor that functions as an essential nutrient and antioxidant, and has been reported to exert potent anti­inflammatory effects. However, the therapeutic potential of PQQ for isoproterenol hydrochloride (Iso)­induced cardiac hypertrophy has not yet been explored, at least to the best of our knowledge. In the present study, the anti­inflammatory effects of PQQ were investigated in Iso­treated AC16 cells, a myocardial injury cellular model characterized by an increase in the apparent surface area of the cells and the activation of intracellular cardiac hypertrophy­associated proteins. The results revealed that pre­treatment with PQQ significantly inhibited the expression of cardiac hypertrophy marker proteins, such as atrial natriuretic peptide, brain natriuretic peptide and ß­myosin heavy chain. PQQ also inhibited the activation of the nuclear factor (NF)­κB signaling pathway in Iso­treated AC16 cells, thus inhibiting the nuclear translocation of NF­κB and reducing the phosphorylation levels of p65. On the whole, the findings of this study suggest that PQQ may be a promising therapeutic agent for effectively reversing the progression of cardiac hypertrophy.

[Clinical impacts of highly active antiretroviral therapy on patients of hemophilia combined with acquired immunodeficiency syndrome: 6-year follow-up of 39 cases].

OBJECTIVE: To evaluate the impact of highly active antiretroviral therapy (HAART) on the haemorrhage status, joint function, and physical ability of the patients of hemophilia combined with acquired immunodeficiency syndrome (AIDS). METHODS: Thirty-nine hemophilia A/AIDS patients, all male, aged (40+/-13), underwent HAART and followed up for 6 years from 2002 to 2008 to observe the yearly hospital visit time, bleeding time, transfusion times, amount of factor VIII transfusion, VIII: C level, physical ability, and joint function. Flow cytometry was used to count the CD4+ T cells, and bDNA assay was used to examine the HIV virus load. RESULTS: The average hospital visit time, bleeding time, transfusion time, and amount of factor VIII transfusion, hemoglobin, white blood cell count, and platelet count before HAART were not significantly different from those after treatment (all P>0.05); only one case showed moderate decrease in VIII: C level, and another one case showed slight decline in physical ability and joint function. The serum HIV RNA load decreased from (4.8+/-1.0) log copies/ml before HAART to (2.4+/-1.0) log copies/ml (P<0.05) and the CD4+ T cell count raised from 183+/-97/mm3 to 456+/-157/mm3 (P<0.05) after HAART. CONCLUSION: HAART has no obvious impact on the haemorrhage status, joint function, and physical ability in hemophilia A/AIDS patients, however, it is effective to inhibit HIV replication and raise CD4+ T cell number which indicates that HAART therapy is positive for immune recovery.

Effects of Illumination Direction on the Surface Potential of CH3NH3PbI3 Perovskite Films Probed by Kelvin Probe Force Microscopy.

The development of organic-inorganic hybrid perovskite solar cells requires critical understanding in the charge-carrier behaviors in the perovskite light absorbers and devices. Kelvin probe force microscopy (KPFM) has been applied as a powerful tool to probe the electrical potential distribution of perovskite films and devices, providing fundamental insights into their charge-carrier properties. When measuring the material photoresponses, various approaches have been employed to illuminate the samples. Here, we measured the surface potential of the layer in the regular mesoporous structure (CH3NH3PbI3/m-TiO2/c-TiO2/FTO) and inverted planar structure (CH3NH3PbI3/NiO/FTO) devices via KPFM. Effects of two representative illumination methods are compared-illumination from top, and from underneath through the transparent glass substrate. By comparing the variation in surface potential under two illumination methods, the surface potential of the perovskite-absorbing layer in a regular structure is higher than that in the inverted structure. The potential difference in two structures implies that the photogenerated charge carriers are injected to the TiO2 electron-transport layer and NiO hole-transport layer, resulting in positive charges and negative charges accumulated in the perovskite-absorbing layer. We demonstrated that the illumination direction has an impact on the surface potential measurement. For the CH3NH3PbI3/TiO2 structure, illumination from underneath facilitates a larger potential change. While for the CH3NH3PbI3/NiO structure with insensitive photoresponse in potential change, the illumination direction has a minor effect.

Efficient and Stable CsPbI3 Solar Cells via Regulating Lattice Distortion with Surface Organic Terminal Groups.

All-inorganic cesium lead iodide perovskites (CsPbI3 ) are promising wide-bandgap materials for use in the perovskite/silicon tandem solar cells, but they easily undergo a phase transition from a cubic black phase to an orthorhombic yellow phase under ambient conditions. It is shown that this phase transition is triggered by moisture that causes distortion of the corner-sharing octahedral framework ([PbI6 ]4- ). Here, a novel strategy to suppress the octahedral tilting of [PbI6 ]4- units in cubic CsPbI3 by systematically controlling the steric hindrance of surface organic terminal groups is provided. This steric hindrance effectively prevents the lattice distortion and thus increases the energy barrier for phase transition. This mechanism is verified by X-ray diffraction measurements and density functional theory calculations. Meanwhile, the formation of an organic capping layer can also passivate the surface electronic trap states of perovskite absorber. These modifications contribute to a stable power conversion efficiency (PCE) of 13.2% for the inverted planar perovskite solar cells (PSCs), which is the highest efficiency achieved by the inverted-structure inorganic PSCs. More importantly, the optimized devices retained 85% of their initial PCE after aging under ambient conditions for 30 days.

Mutation of the nm23-H1 gene has a non-dominant role in colorectal adenocarcinoma.

Nm23-H1 is a metastasis suppressor gene, which is has a reduced expression in patients with digestive system cancer. However, the mechanistic basis for the genetic instability remains unknown. To study the expression of the nm23-H1 gene in patients with colorectal cancer, polymerase chain reaction-single strand conformation polymorphism was used to analyze any point mutation, and immunohistochemistry was used to detect the expression of nm23-H1. Results revealed that all 63 specimens of Chinese human colorectal cancer tissues exhibit no point mutation. Among those 63 specimens, 19 (30%) exhibited positive immunostaining for the nm23-H1 protein and 44 (70%) exhibited negative immunostaining. These observations suggested that the protein and gene expression levels of nm23-H1 are reduced in colorectal cancer compared with the adjacent normal tissues, and the point mutation in the nm23-H1 gene is not the dominant cause of metastatic colorectal cancer.

USO1 promotes tumor progression via activating Erk pathway in multiple myeloma cells.

OBJECTIVE: This study aimed to explore the influence of USO1 on multiple myeloma (MM) cell proliferation and apoptosis and the related molecular mechanism. METHODS: The expression of USO1 and MIF in MM tissues and cells, normal bone marrow tissues and cells were determined by qRT-PCR and western blot assay. The cell proliferation and apoptosis of MM cells before and after knockdown of USO1 were determined by MTT assay and flow cytometry, respectively. Before and after knockdown of USO1, the expression of the proliferation-related genes cyclin D1, Mcm2 and PCNA in MM cells was determined by qRT-PCR and western blot assay. The protein level of p-Erk1/2 and MIF was determined by western blot assay and ELISA, respectively. RESULTS: The expression levels of USO1 and MIF in MM tissues and cells were much higher than those in normal bone marrow tissues and cells. Knockdown of USO1 resulted in the inhibited ability of cell proliferation and induced cell apoptosis. The expression of cyclin D1, Mcm2, PCNA and p-Erk1/2 decreased significantly after knockdown of USO1 as well as the decreased MIF secretion. CONCLUSION: USO1 gene may be a promising target for the therapy of human MM and its diagnosis marker.

Promoter methylation of the DLC­1 gene and its inhibitory effect on human colon cancer.

Deleted in liver cancer­1 (DLC­1), a candidate tumor suppressor gene which is inactive in liver carcinogenesis, is located at 8p21.3, where deletions are frequently found in several types of human cancer. Promoter hypermethylation is an epigenetic mechanism leading to silencing of the gene expression, which may be the primary cause for the absence of DLC­1. We investigated the expression of the DLC­1 gene and the methylation of the DLC­1 gene in colon cancer cell lines (Caco­2, LoVo and HT­29). The data showed that reduced or undetectable levels of DLC­1 mRNA were found in HT­29 by reverse transcription-polymerase chain reaction (RT­PCR). By contrast, the DLC­1 gene was significantly expressed in Caco­2 and LoVo cells. These findings were in agreement with the data obtained from western blot analysis. To further determine whether aberrant methylation is a contributing factor to transcriptional inactivation of DLC­1 in HT­29, the methylation of promoter was examined using methylation­specific PCR and sodium bisulfite genomic sequencing in LoVo and HT­29 cells, which suggests that promoter hypermethylation accounts for silencing of the DLC­1 gene in HT­29 cells. Since DLC­1 is a candidate tumor suppressor gene, we sought to determine whether DLC­1 expression is associated with cell proliferation in colon cancer cell lines. RNA interference techniques were adopted to inhibit DLC­1 expression in the LoVo cell line and resulted in inhibition of cell growth and reduced colony formation. Collectively, our observations suggest that hypermethylation is responsible for abrogating the function of the DLC­1 gene in colon cancer and indicate a role of DLC­1 in colon carcinogenesis.

Inhibition of nm23-H1 gene expression in chronic myelogenous leukemia cells.

For solid tumors of a malignant origin, the expression of the nm23-H1 gene is a positive prognostic factor. However, for chronic myeloid leukemia (CML), the prognostic role of nm23-H1 gene expression is unknown. The present study investigated the impact of nm23-H1 gene expression on the proliferation and migration of the CML K562 cell line to elucidate the association between nm23-H1 gene expression and CML cell survival. An RNAi lipo-recombinant plasmid of the nm23-H1 gene (pGCsi-nm23-H1) was constructed and transfected into the K562 cells. RT-PCR and western blotting were used to detect nm23-H1 mRNA and protein expression, respectively. The anchorage-independent growth ability of the transfected cells was observed in soft agar culture and the ability of the K562 cells to migrate was determined using a Transwell assay. Following the successful construction and transfection of the pGCsi-nm23-H1 plasmid into the K562 cells, nm23-H1 mRNA and protein expression levels were significantly lower compared with the control group. The stably-transfected pGCsi-nm23-H1 K562 cells exhibited a markedly increased ability to form colonies and the number and sizes of the colonies were significantly increased compared with those of the control. In vitro, the cells migrated through a Matrigel-coated membrane during incubation for 20 h. The Transwell assay revealed that the quantitative number of pGCsi-nm23-H1 K562 cells that migrated into the lower compartment of the invasion chamber was markedly increased compared with the control. In conclusion, nm23-H1 gene expression may inhibit K562 cell proliferation and migration. nm23-H1 may be a cancer suppressor gene and play a significant role in inhibiting the survival of CML cells.

Defective expression and modulation of B7-2/CD86 on B cells in B cell chronic lymphocytic leukemia.

Malignant monoclonal B cells of chronic B cell lymphocytic leukemia (B-CLL) usually fail to be cleared, which indicates important costimulatory molecules may be lacking. Among those costimulatory signals, B7-1/CD80 and B7-2/CD86 caused utmost attention. In this study, B7-1 and B7-2 expression on B cells in chronic B cell lymphocytic leukemia patients were detected. Data showed that B7-2 expression in chronic B cell lymphocytic leukemia patients is significantly lower than in normal people, which suggests defective B7-2 expression may be one of the pathogenic mechanisms of chronic B cell lymphocytic leukemia. Further, we confirmed interferon-gamma could induce B7-2 expression slightly and promote T-cell response against chronic B cell lymphocytic leukemia cells, indicating interferon-gamma has clinical value in chronic leukemia immunotherapy based on modulating B7-2 expression.