Silencing of HMGA1 expression by RNA interference suppresses growth of osteogenic sarcoma

The expression of high mobility group protein A1 (HMGA1) protein has been closely related to various malignant and prognostic degrees of tumor. To investigate the influence of down-regulating HMGA1 on the tumor and the mechanism underlying antitumor of HMGA1, we transfected the HMGA1 shRNA vector into the osteogenic sarcoma MG-63 cell and observed the changes of cell proliferation, invasion abilities, and the tumor growth. HMGA1 gene expression could be efficiently inhibited, and cell proliferation, migration, invasion, and matrix metalloprotease level were also decreased. BALB/C nude mice injected with the MG-63 cells transfected HMGA1 shRNA showed the significant lower tumor weight, tumor volume, and longer tumor-forming time compared with the control group. Our results suggest that knockdown of HMGA1 could inhibit growth and metastasis potentials of MG-63 cells, which may be a therapeutic target protein for osteogenic sarcoma and may be of biological importance.     

Dendritic cell co-transfected with FasL and allergen genes induces T cell tolerance and decreases airway inflammation in allergen induced murine model

Dendritic cell (DC) displays tremendous functional plasticity in response to antigens and plays important roles in inducing immune tolerance. In this study, we investigated the effects of immature DC (imDC) co-transfected with FasL and allergen Der p2 genes (FasL-Der p2-DC) on inducing immune tolerance and modulating airway inflammation of Der p2-induced allergic mice. Moreover, we compared the effects of FasL-Der p2-DC with FasL-transfected imDC (FasL-DC) and Der p2-transfected imDC (Der p2-DC) respectively. Results showed that FasL-Der p2-DC and Der p2-pulsed FasL-DC induced T cell unresponsiveness to Der p2 via apoptosis. Der p2-DC could induce T cell hyporesponsiveness to Der p2. FasL-Der p2-DC, FasL-DC and Der p2-DC could inhibit Th2 response and reduce allergic airway inflammation. FasL-Der p2-DC was more effective than FasL-DC and Der p2-DC, respectively. These results demonstrate that FasL and allergen genes co-expressing DC might be a promising approach to allergy therapy.     

Comparative analysis of transposable elements in the melanogaster subgroup sequenced genomes

Transposable elements (TEs) are indwelling components of genomes, and their dynamics have been a driving force in genome evolution. Although we now have more information concerning their amounts and characteristics in various organisms, we still have little data from overall comparisons of their sequences in very closely-related species. While the Drosophila melanogaster genome has been extensively studied, we have only limited knowledge regarding the precise TE sequences in the genomes of the related species Drosophila simulans, Drosophila sechellia and Drosophila yakuba. In this study we analyzed the number and structure of TE copies in the sequenced genomes of these four species. Our findings show that, unexpectedly, the number of TE insertions in D. simulans is greater than that in D. melanogaster, but that most of the copies in D. simulans are degraded and in small fragments, as in D. sechellia and D. yakuba. This suggests that all three species were invaded by numerous TEs a long time ago, but have since regulated their activity, as the present TE copies are degraded, with very few full-length elements. In contrast, in D. melanogaster, a recent activation of TEs has resulted in a large number of almost-identical TE copies. We have detected variants of some TEs in D. simulans and D. sechellia, that are almost identical to the reference TE sequences in D. melanogaster, suggesting that D. melanogaster has recently been invaded by active TE variants from the other species. Our results indicate that the three species D. simulans, D. sechellia, and D. yakuba seem to be at a different stage of their TE life cycle when compared to D. melanogaster. Moreover, we show that D. melanogaster has been invaded by active TE variants for several TE families likely to come from D. simulans or the ancestor of D. simulans and D. sechellia. The numerous horizontal transfer events implied to explain these results could indicate introgression events between these species.     

Comparative analysis of mycobacterial NADH pyrophosphatase isoforms reveals a novel mechanism for isoniazid and ethionamide inactivation

NADH pyrophosphatase (NudC) catalyses the hydrolysis of NAD(H) to AMP and NMN(H) [nicotinamide mononucleotide (reduced form)]. NudC multiple sequence alignment reveals that homologues from most Mycobacterium tuberculosis isolates, but not other mycobacterial species, have a polymorphism at the highly conserved residue 237. To elucidate the functional significance of this polymorphism, comparative analyses were performed using representative NudC isoforms from M. tuberculosis H37Rv (NudC(Rv)) and M. bovis BCG (NudC(BCG)). Biochemical analysis showed that the P237Q polymorphism prevents dimer formation, and results in a loss of enzymatic activity. Importantly, NudC(BCG) was found to degrade the active forms of isoniazid (INH), INH-NAD and ethionamide (ETH), ETH-NAD. Consequently, overexpression of NudC(BCG) in Mycobacterium smegmatis mc(2)155 and M. bovis BCG resulted in a high level of resistance to both INH and ETH. Further genetic studies showed that deletion of the nudC gene in M. smegmatis mc(2)155 and M. bovis BCG resulted in increased susceptibility to INH and ETH. Moreover, inactivation of NudC in both strains caused a defect in drug tolerance phenotype for both drugs in exposure assays. Taken together, these data suggest that mycobacterial NudC plays an important role in the inactivation of INH and ETH.     

Quantitative evaluation of heavy metals' pollution hazards in liquefaction residues of sewage sludge

Liquefaction residues (LR) are the main by-products of sewage sludge (SS) liquefaction. This study quantitatively evaluates the potential ecological risk and pollution degrees of heavy metals (Pb, Zn, Cu, Cd, Cr and Ni) in LR versus SS. The leaching rates (R1) of heavy metals in LR were much lower than those in SS, revealing that the mobility/leachability of heavy metals was well suppressed after liquefaction. Geo-accumulation index (Igeo) indicated that the liquefaction process significantly weakened the contamination degrees of heavy metals. Potential ecological risk index (RI) demonstrated that overall risks caused by heavy metals were obviously lowered from 1093.56 (very high risk) in SS to 4.72 and 1.51 (low risk) in LR1 and LR2, respectively. According to the risk assessment code (RAC), each tested heavy metal had no or low risk to the environments after liquefaction. In a word, the pollution hazards of heavy metals in LR were markedly mitigated.     

Secoiridoid glucosides and related compounds from Syringa reticulata and their antioxidant activities

A 70% EtOH extract from the bark of Syringareticulata has shown significant antioxidant activity. Chemical study on the extract resulted in the isolation of seventeen compounds (1-17), including a novel oleoside-type secoiridoid glucoside, reticuloside (1), and the structures were elucidated on the basis of extensive spectroscopic analyses. Among the isolated compounds, jaspolyoside (2), oleuropein (4) and 2-(3,4-dihydroxy)-phenylethyl-β-d-glucopyranoside (17), showed the most potent superoxide anion scavenging activity with the EC(50) values of 4.97, 2.57 and 4.97μM, respectively. The structure-activity relationship indicated that the presence of 2-(3,4-dihydroxyphenyl)-ethoxy group is important for exhibiting the activity.     

Marek's disease virus type 1 microRNA miR-M3 suppresses cisplatin-induced apoptosis by targeting Smad2 of the transforming growth factor beta signal pathway

Viruses cause about 15% of the cancers that are still the leading causes of human mortality. The discovery of viral oncogenes has enhanced our understanding of viral oncogenesis. However, the underlying molecular mechanisms of virus-induced cancers are complex and require further investigation. The present study has attempted to investigate the effects of the microRNAs (miRNAs) encoded by Marek's disease virus 1 (MDV1), a chicken herpesvirus causing acute T-cell lymphomas and solid visceral tumors in chickens, on anti-cancer drug-induced apoptosis and identify the targets of the miRNAs. The results showed that of the total 14 miRNAs encoded by MDV1, MDV1-miR-M3 significantly promoted cell survival under treatment with cisplatin, a widely used chemotherapy drug. MDV1-miR-M3 suppressed cisplatin-induced apoptosis by directly downregulating expression at the protein but not the mRNA level of Smad2, a critical component in the transforming growth factor β signal pathway. Our data suggest that latent/oncogenic viruses may encode miRNAs to directly target cellular factors involved in antiviral processes including apoptosis, thus proactively creating a cellular environment beneficial to viral latency and oncogenesis. Furthermore, the knowledge of the apoptosis resistance conferred by viral miRNAs has great practical implications for improving the efficacy of chemotherapies for treating cancers, especially those induced by oncogenic viruses.     

Triterpenes and neolignans from the roots of Nannoglottis carpesioides

Seven oleanane-type triterpenes and two 8-O-4′-neolignans, along with five known compounds (three 28-noroleanane-type triterpenes, one sarratane triterpene, and one neolignan), were isolated from roots of Nannoglottis carpesioides. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR, HRMS, and CD. The absolute configurations of two triterpenes were determined by experimental and calculated circular dichroism (CD) and optical rotation values. Ten compounds were evaluated for their cytotoxicity against human promyelocytic leukaemia (HL-60) and human hepatoma (Hep-G2) cells using the MTT assay. The antioxidant activities of these compounds were assessed by ABTS radical-scavenging assays. Among the tested compounds, three compounds exhibited moderate radical-scavenging activity against ABTS⁺, with IC₅₀ values of 22.4, 17.4, and 23.2 μM, respectively.