The cytotoxicity and anticancer mechanisms of alterporriol L, a marine bianthraquinone, against MCF-7 human breast cancer cells

Alterporriol L, a new bianthraquinone derivative, was isolated from a marine fungus Alternaria sp. ZJ9-6B. The cytotoxic activity and anticancer mechanisms of alterporriol L towards breast cancer cells lines were detected using MTT assay, immunofluorescence, and flow cytometry. Simultaneously, the changes in morphological properties of cells were detected before and after treatment with alterporriol L by atomic force microscope (AFM) at a nanometer scale. MTT assay showed that alterporriol L could effectively inhibit the growth and proliferation, and there was a dose-dependent manner of cell death. Moreover, the alterporriol L could induce cancer cell apoptosis or necrosis. Furthermore, the reactive oxygen species, mitochondrial membrane potential, and cytosolic free calcium level were changed after treatment with alterporriol L, suggesting that alterporriol L played vital roles in breast cancer cells through destroying the mitochondrial. And all these alterations are in accord with changes of morphology detected by AFM, which suggested that the AFM is a useful tool to detect the morphological changes of the cancer cells.     

Reproductive function of Selenoprotein M in Chinese mitten crabs (Eriocheir sinesis)

Selenoproteins are present in all major forms of life, including eukaryotes, bacteria and archaea. In eukaryotic animals, selenoproteins often function as antioxidants, but rare or absent in other phyla, such as plants and fungi (except for the green alga Chlamydomonas). Selenoprotein M (SelM) is a selenocysteine containing protein with redox activity, which is involved in the antioxidant response. However, information remains limited about SelM physiology and function in marine invertebrates, particularly in crustaceans. Hence, we investigated the reproductive functionality of SelM in the Chinese mitten crab (Eriocheir sinensis), which is a commercially important yet disease vulnerable aquaculture species. The full-length SelM cDNA (928bp) strand was cloned by using PCR, based on an initial expressed sequence tag (EST) that was isolated from a hepatopancreatic cDNA library. The SelM cDNA contained a 390bp open reading frame (ORF) that encoded a putative 129 amino acid (aa) protein. SelM mRNA expression in E. sinensis was (a) tissue-specific, with the highest expression observed in the hepatopancreas, testis, ovaries and intestines. Based on this information, we then detected the different stages of tissue expression for SelM in the testis, ovary, and male crab hepatopancreas and hemolymph, and the enzyme activity of SelM in the testis. Overall, SelM was isolated successfully from the Chinese mitten crab, and its involvement in the regulation of reproduction during the period of rapid development in E. sinensis was confirmed.     

Nodal induces apoptosis through activation of the ALK7 signaling pathway in pancreatic INS-1 β-cells

We demonstrated previously that the activation of ALK7 (activin receptor-like kinase-7), a member of the type I receptor serine/threonine kinases of the TGF-β superfamily, resulted in increased apoptosis and reduced proliferation through suppression of Akt signaling and the activation of Smad2-dependent signaling pathway in pancreatic β-cells. Here, we show that Nodal activates ALK7 signaling and regulates β-cell apoptosis. We detected Nodal expression in the clonal β-cell lines and rodent islet β-cells. Induction of β-cell apoptosis by treatment with high glucose, palmitate, or cytokines significantly increased Nodal expression in clonal INS-1 β-cells and isolated rat islets. The stimuli induced upregulation of Nodal expression levels were associated with elevation of ALK7 protein and enhanced phosphorylated Smad3 protein. Nodal treatment or overexpression of Nodal dose- or time-dependently increased active caspase-3 levels in INS-1 cells. Nodal-induced apoptosis was associated with decreased Akt phosphorylation and reduced expression level of X-linked inhibitor of apoptosis (XIAP). Remarkably, overexpression of XIAP or constitutively active Akt, or ablation of Smad2/3 activity partially blocked Nodal-induced apoptosis. Furthermore, siRNA-mediated ALK7 knockdown significantly attenuated Nodal-induced apoptosis of INS-1 cells. We suggest that Nodal-induced apoptosis in β-cells is mediated through ALK7 signaling involving the activation of Smad2/3-caspase-3 and the suppression of Akt and XIAP pathways and that Nodal may exert its biological effects on the modulation of β-cell survival and β-cell mass in an autocrine fashion.     

Fluazinam targets mitochondrial complex I to induce reactive oxygen species-dependent cytotoxicity in SH-SY5Y cells

Although the underlying cause of Parkinson's disease (PD) is not well characterized, epidemiological studies suggest that exposure to agricultural chemicals is a risk factor for PD. Fluazinam (FZN) is a new active ingredient for the control of grey mould, belonging to the novel broad spectrum phenylpyridinamine fungicides. We used human neuroblastoma SH-SY5Y cells to investigate mechanisms of dopaminergic cell death in response to FZN. FZN treatment produced dose-dependent cytotoxicity, and decreased the tyrosine hydroxylase (TH) expression in SH-SY5Y cells. We provided evidence for the occurrence of oxidative stress and oxidative damage during FZN exposure on dopaminergic cells through the measurement of reactive oxygen species (ROS) in cells with DCFH-DA. The cytotoxic effects of FZN appear to involve an increase in ROS generation since pretreatment with N-acetyl cysteine (NAC), an anti-oxidant, reduced cell death. After FZN treatment, dopamine (DA) levels decreased in both cell and culture media, and oxidative effects of FZN were blocked by NAC pretreatment. We show that cell death in response to FZN was due to apoptosis since FZN exposure results in an increased in cytochrome c release into the cytosol and activated caspase-3 through p38 and JNK signaling. Furthermore, the blocking of p38 or JNK signaling inhibits FZN-induced cell death. Phosphorylation of mitogen-activated protein kinases precedes cytochrome c release and caspase-3 activation. This cellular response is characteristic of mitochondrial dysfunction. Therefore, we also investigated the effect of FZN on mitochondrial complex I activity in FZN-treated cell. Interestingly, we show that FZN inhibited the complex I activity. Thus in this study, we report a new mode of action by which the fungicide FZN could triggers apoptosis.     

The effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on rat testicular function

Wireless mobile phones and other telecommunication devices are used extensively in daily life. We therefore examined the effects of combined exposure to radiofrequency electromagnetic fields (RF‐EMF) on rat testicular function, specifically with respect to sensitive processes such as spermatogenesis. Male rats were exposed to single code division multiple access (CDMA) and wideband code division multiple access (WCDMA) RF signals for 12 weeks. The RF exposure schedule comprised 45 min/day, 5 days/week for a total of 12 weeks. The whole‐body average specific absorption rate (SAR) of CDMA and WCDMA was 2.0 W/kg each or 4.0 W/kg in total. We then investigated the correlates of testicular function such as sperm count in the cauda epididymis, testosterone concentration in the blood serum, malondialdehyde concentrations in the testes and epididymis, frequency of spermatogenesis stages, and appearance of apoptotic cells in the testes. We also immunoblotted for p53, bcl2, GADD45, cyclin G, and HSP70 in the testes of sham‐ and combined RF‐exposed animals. Based on the results, we concluded that simultaneous exposure to CDMA and WCDMA RF‐EMFs at 4.0 W/kg SAR did not have any observable adverse effects on rat spermatogenesis. Bioelectromagnetics 33:356–364, 2012. © 2011 Wiley Periodicals, Inc.     

Research progress on banana functional genomics involved in fruit quality

Banana is one of the most important tropical fruits and main economical resource for tropical people. Banana quality is always becoming a focus for people to follow with interest. Here, we reviewed recent research progresses on isolation and identification of banana genes involved in fruit quality such as ripening, softening, glycometabolism, and scent, which will help us explore their functions and facilitate banana quality improvement.     

Protective Effects of Adeno-associated Virus Mediated Brain-derived Neurotrophic Factor Expression on Retinal Ganglion Cells in Diabetic Rats

Adeno-associated virus vector plasmid carrying the expression cassette of brain-derived neurotrophic factor (BDNF), pAAV-BDNF, was constructed and packaged into recombinant adeno-associated virus (rAAV-BDNF). The rAAV-BDNF was intravitreally injected into streptzotocin (STZ)-induced diabetic Sprague–Dawley (SD) Rats. Data showed that over-expression of BDNF could increase alive retinal ganglion cell (RGC) number and improve its function in streptzotocin(STZ)-induced diabetic rats, which might be a new method to treat diabetic neuropathy and retinopathy.     

Modeling Seasonal Rabies Epidemics in China

Human rabies, an infection of the nervous system, is a major public-health problem in China. In the last 60 years (1950–2010) there had been 124,255 reported human rabies cases, an average of 2,037 cases per year. However, the factors and mechanisms behind the persistence and prevalence of human rabies have not become well understood. The monthly data of human rabies cases reported by the Chinese Ministry of Health exhibits a periodic pattern on an annual base. The cases in the summer and autumn are significantly higher than in the spring and winter. Based on this observation, we propose a susceptible, exposed, infectious, and recovered (SEIRS) model with periodic transmission rates to investigate the seasonal rabies epidemics. We evaluate the basic reproduction number R ₀, analyze the dynamical behavior of the model, and use the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health. We also carry out some sensitivity analysis of the basic reproduction number R ₀ in terms of various model parameters. Moreover, we demonstrate that it is more reasonable to regard R ₀ rather than the average basic reproduction number [`(R)]₀\bar{R}_{0} or the basic reproduction number [^(R)]₀\hat{R}_{0} of the corresponding autonomous system as a threshold for the disease. Finally, our studies show that human rabies in China can be controlled by reducing the birth rate of dogs, increasing the immunization rate of dogs, enhancing public education and awareness about rabies, and strengthening supervision of pupils and children in the summer and autumn.     

Characterization of the proteomic profiles of the brown tide alga Aureoumbra lagunensis under phosphate- and nitrogen-limiting conditions and of its phosphate limitation-specific protein with alkaline phosphatase activity

The persistent bloom of the brown tide alga Aureoumbra lagunensis has been reported in coastal embayments along southern Texas, but the molecular mechanisms that sustain such algal bloom are unknown. We compared the proteome and physiological parameters of A. lagunensis grown in phosphate (P)-depleted, P- and nitrogen (N)-depleted, and nutrient-replete cultures. For the proteomic analysis, samples from three conditions were subjected to two-dimensional electrophoresis and tandem mass spectrometry analysis. Because of the paucity of genomic resources in this species, a de novo cross-species protein search was used to identify the differentially expressed proteins, which revealed their involvement in several key biological processes, such as chlorophyll synthesis, antioxidative protection, and protein degradation, suggesting that A. lagunensis may adopt intracellular nutrient compensation, extracellular organic nutrient regeneration, and damage protection to thrive in P-depleted environments. A highly abundant P limitation-specific protein, tentatively identified as a putative alkaline phosphatase, was further characterized by enzyme activity assay on nondenaturing gel and confocal microscopy, which confirmed that this protein has alkaline phosphatase activity, is a cytoplasmic protein, and is closely associated with the cell membrane. The abundance, location, and functional expression of this alkaline phosphatase all indicate the importance of organic P utilization for A. lagunensis under P limitation and the possible role of this alkaline phosphatase in regenerating phosphate from extra- or intracellular organic phosphorus.