Effect of α-momordicine on proliferation and apoptosis of liver cancer, and its associated mechanisms of action

Purpose: To investigate the effect of α-momordicine (α-MMC) on liver cancer cell proliferation and apoptosis, and to elucidate the mechanisms of action involved. Methods: In in vitro experiments, hepatoma cell lines were used, while nude mice with hepatocellular carcinoma were used for in vivo studies. Cancer cell proliferation was determined using MTT assay while apoptosis was assayed by flow cytometry and TUNNEL staining. Gene expression was determined with real-time polymerase chain reaction (RT-PCR), while protein expression levels were assayed by Western blot, immunohistochemistry and immunofluorescence. Results: Alpha-MMC decreased HCC cell viability dose-dependently (p < 0.05). In HepG2 cells, G2/M cell cycle was halted after 48 h intervention with 1.24 mg/mL α-MMC. However, at G0/G1 phase, αMMC at doses of 1.06 and 0.92 mg/mL caused cell cycle arrest of HCC-LM3 and SMMC-7721 cells. In vivo studies showed that after establishment of the nude mice liver cancer model, exposure to α-MMC at a dose of 0.70 mg/kg or 2.08mg/kg for 4 weeks reduced the size of liver cancer in the treatment group, relative to control group; mean diameter of liver cancer decreased from 2.16 to 0.51 cm, while mean volume decreased from 1.185 to 0.085 cm3 . Moreover, α-MMC increased apoptosis level in liver cancer tissues in nude mice, and down-regulated the expressions of P-AKT, RAGE, MMP-9 and HMGB1, but upregulated Bax/Bcl2 ratio (p < 0.05). Conclusion: α-MMC inhibits cancer cell growth and proliferation, and facilitates their apoptosis by positively regulating the ratio of Bax/Bcl2. The anti-liver cancer effect of α-MMC is mediated via HMGB1-RAGE and AKT signaling pathway

Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes

BACKGROUND: An effective vaccine and new therapeutic methods for hepatitis C virus (HCV) are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI). Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens. RESULTS: A recombinant replication-defective adenovirus serotype 5 (rAd5) vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1-746 amino acid HCV 1b subtype). Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m.), intranasal injection (i.n.), or intradermal injection (i.d.) and boosted using a different combination of injection routes. CMI was evaluated via IFN-γ ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2) was elicited and remained at a high level for a long period (16 weeks post-vaccination) in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross-protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a) vaccinia virus. CONCLUSIONS: Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates

Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration

The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA

Inverse Symmetry in Complete Genomes and Whole-Genome Inverse Duplication

The cause of symmetry is usually subtle, and its study often leads to a deeper understanding of the bearer of the symmetry. To gain insight into the dynamics driving the growth and evolution of genomes, we conducted a comprehensive study of textual symmetries in 786 complete chromosomes. We focused on symmetry based on our belief that, in spite of their extreme diversity, genomes must share common dynamical principles and mechanisms that drive their growth and evolution, and that the most robust footprints of such dynamics are symmetry related. We found that while complement and reverse symmetries are essentially absent in genomic sequences, inverse–complement plus reverse–symmetry is prevalent in complex patterns in most chromosomes, a vast majority of which have near maximum global inverse symmetry. We also discovered relations that can quantitatively account for the long observed but unexplained phenomenon of -mer skews in genomes. Our results suggest segmental and whole-genome inverse duplications are important mechanisms in genome growth and evolution, probably because they are efficient means by which the genome can exploit its double-stranded structure to enrich its code-inventory

Core cis-element variation confers subgenome-biased expression of a transcription factor that functions in cotton fiber elongation

Cotton cultivars have evolved to produce extensive, long, seed-born fibers important for the textile industry, but we know little about the molecular mechanism underlying spinnable fiber formation. Here, we report how PACLOBUTRAZOL RESISTANCE 1 (PRE1) in cotton, which encodes a basic helix-loop-helix (bHLH) transcription factor, is a target gene of spinnable fiber evolution. Differential expression of homoeologous genes in polyploids is thought to be important to plant adaptation and novel phenotypes. PRE1 expression is specific to cotton fiber cells, upregulated during their rapid elongation stage and A-homoeologous biased in allotetraploid cultivars. Transgenic studies demonstrated that PRE1 is a positive regulator of fiber elongation. We determined that the natural variation of the canonical TATA-box, a regulatory element commonly found in many eukaryotic core promoters, is necessary for subgenome-biased PRE1 expression, representing a mechanism underlying the selection of homoeologous genes. Thus, variations in the promoter of the cell elongation regulator gene PRE1 have contributed to spinnable fiber formation in cotton. Overexpression of GhPRE1 in transgenic cotton yields longer fibers with improved quality parameters, indicating that this bHLH gene is useful for improving cotton fiber quality

Correction Method for the Readout Saturation of the DAMPE Calorimeter

The DArk Matter Particle Explorer (DAMPE) is a space-borne high energy cosmic-ray and $\gamma$-ray detector which operates smoothly since the launch on December 17, 2015. The bismuth germanium oxide (BGO) calorimeter is one of the key sub-detectors of DAMPE used for energy measurement and electron proton identification. For events with total energy deposit higher than decades of TeV, the readouts of PMTs coupled on the BGO crystals would become saturated, which results in an underestimation of the energy measurement. Based on detailed simulations, we develop a correction method for the saturation effect according to the shower development topologies and energies measured by neighbouring BGO crystals. The verification with simulated and on-orbit events shows that this method can well reconstruct the energy deposit in the saturated BGO crystal.Comment: 17 pages, 9 figures, to be published in Nuclear Inst. and Methods in Physics Research,

Developing a Model for Chloride Ions Transport in Cement Concrete under Dynamic Flexural Loading and Dry-Wet Cycles

Chloride ions attack is the main factor leading to the degradation of concrete durability, while the diffusion process would be significantly aggravated under the dynamic flexural loading and dry-wet cycles. In this paper, the influence coefficients of dynamic flexural loading on chloride/water diffusion coefficients were established, based on the relationship between the dynamic flexural loading and the chloride ions diffusion coefficient of concrete. Based on the model of chloride ions transporting in dry-wet cycle environment, the transport model of chloride ions in concrete under the dynamic flexural loading and dry-wet cycles was established. The effects of different factors on the chloride ions transport law in concrete were analyzed through laboratory test. The results showed that the model was in good agreement with the experimental results. The theory and assumptions proposed applied in the model of chloride ions transport in concrete under the dynamic flexural loading and dry-wet cycles had certain rationality and scientificity

Black Holes as the source of the dark energy: a stringent test with the high-redshift JWST AGNs

It has been suggested that there is evidence for cosmological coupling of black holes (BHs) with an index of $k\approx 3$ and hence the BHs serve as the astrophysical source of the dark energy. The data sample however is limited for the redshifts $\leq 2.5$. Recently, the James Webb Space Telescope (JWST) has detected more than 180 high-redshift Active Galactic Nuclei (AGNs) and quasars. Among the JWST NIRSpec/NIRCam resolved AGNs, three are identified in early-type host galaxies with a redshift $z\sim 4.5-7$. Their $M_{\star}$ and $M_{\rm BH}$, however, are in tension with the prediction of the cosmological coupling of black holes with $k=3$ at a confidence level of $\sim 3\sigma$, which is not in support of the hypothesis that BHs serve as the origin of dark energy. The future observations of high-redshift AGNs by JWST will further test such a hypothesis by identifying more early-type host galaxies in the higher mass range.Comment: 9 pages, 3 figures, 1 table; Submitted to ApJL. Comments are welcome

Genetic dissection of QTLs for oil content in four maize DH populations

Oil is one of the main components in maize kernels. Increasing the total oil content (TOC) is favorable to optimize feeding requirement by improving maize quality. To better understand the genetic basis of TOC, quantitative trait loci (QTL) in four double haploid (DH) populations were explored. TOC exhibited continuously and approximately normal distribution in the four populations. The moderate to high broad-sense heritability (67.00-86.60%) indicated that the majority of TOC variations are controlled by genetic factors. A total of 16 QTLs were identified across all chromosomes in a range of 3.49-30.84% in term of phenotypic variation explained. Among them, six QTLs were identified as the major QTLs that explained phenotypic variation larger than 10%. Especially, qOC-1-3 and qOC-2-3 on chromosome 9 were recognized as the largest effect QTLs with 30.84% and 21.74% of phenotypic variance, respectively. Seventeen well-known genes involved in fatty acid metabolic pathway located within QTL intervals. These QTLs will enhance our understanding of the genetic basis of TOC in maize and offer prospective routes to clone candidate genes regulating TOC for breeding program to cultivate maize varieties with the better grain quality