Activity and characterization of mixed organic compounds extracted from Rhodobacter sphaeroides as alternative materials to serum for mammalian cell growth

Photosynthetic microorganisms produce relatively large amounts of physiologically active materials which stimulate the physiological activity of other organisms. In this study, mammalian HeLa cells were cultured in different culture media which were Dulbecco's modified Eagle medium (DMEM) with newborn calf serum (NCS), and DMEM including different types of physiologically activating compounds (PACs) extracted from Rhodobacter sphaeroides grown under various culture conditions. R. sphaeroides was grown under the following five different culture conditions: anaerobically in the light, anaerobically in the dark and treated with dimethyl sulfoxide, aerobically in the dark for 48 h, in the light for 48 h, and in the light for 24 h and changed after previous culturing in the dark for 24 h. The growth of HeLa cell was measured by cell counting using a hemocytometer, and the fluorescent intensities of cellular lysosomes were measured to check the level of cellular stress caused by adding PACs. The growth of HeLa cells cultured in DMEM with PACs extracted from R. sphaeroides aerobically grown under dark conditions was enhanced compared to that of cells grown with NCS. We also found that a high concentration of pigments such as bacteriochlorophylls and carotenoids and a high concentration of arginine produced by R. sphaeroides aerobically grown in the dark were implicated in increased growth of the HeLa cells. Therefore, our results suggest that PACs extracted from R. sphaeroides aerobically cultured in dark conditions can enhance the physiological activity of mammalian cells and serve as nontoxic and bioavailable materials.     

Synthesis and biological evaluation of 4-piperidinecarboxylate and 4-piperidinecyanide derivatives for T-type calcium channel blockers

To obtain selective and potent inhibitor for T-type calcium channel by ligand based drug design, 4-piperidinecarboxylate and 4-piperidinecyanide derivatives were prepared and evaluated for in vitro and in vivo activity against α(1G) calcium channel. Among them, several compounds showed good T-type calcium channel inhibitory activity and minimal off-target activity over hERG channel (% inhibition at 10 μM=61.85-71.99, hERG channel IC(50)=1.57 ± 0.14-4.98 ± 0.36 μM). Selected compound 31a was evaluated on SNL model of neuropathic pain and showed inhibitory effect on mechanical allodynia.     

Preparation, in vitro screening and molecular modelling of symmetrical 4-tert-butylpyridinium cholinesterase inhibitors--analogues of SAD-128

Carbamate inhibitors (e.g., pyridostimine bromide) are used as a pre-exposure treatment for the prevention of organophosphorus poisoning. They work by blocking acetylcholinesterase’s (AChE) native function and thus protect AChE against irreversible inhibition by organophosphorus compounds. However, carbamate inhibitors are known for many undesirable side-effects related to the carbamylation of AChE. In this Letter, 19 analogues of SAD-128 were prepared and evaluated as cholinesterase inhibitors. The screening results showed promising inhibitory ability of four compounds better to used standards (pralidoxime, obidoxime, BW284c51, ethopropazine, SAD-128). Four most promising compounds were selected for further molecular docking studies. The SAR was stated from obtained data. The former receptor studies were reported and discussed. The further in vivo studies were recommended in the view of OP pre-exposure treatment.     

Moth olfactory trichoid sensilla exhibit nanoscale-level heterogeneity in surface lipid properties

Chemical force microscopy (CFM) based on tapping mode Atomic force microscopy (AFM) utilized with topographic and phase-shift analyses was used to investigate the topography and surface chemical properties, respectively, of the long trichoid sensilla on the antennae of male Helicoverpa zea. AFM topographic imaging revealed regular series of step-ridges along nearly the entire length of each sensillum, except for the basal ca. 1/3 portions, which were devoid of such ridges. Inter-ridge regions were flat, with regularly spaced pores, ca. 30 nm in diameter populating these planar areas. Many pores exhibited a raised dome that often nearly completely spanned the depression, with only the edges of the depressed portion of the pore still visible. Some pores were observed also along the bases of the ridges. CFM probing of the surface for chemical interactions with the SiO₂ hydrophilic tip revealed consistently diminished hydrogen bonding of the ridge edge areas with the tip than along the flat planar inter-ridge regions. Surfaces of domes over the pores also tended to have less hydrogen bonding with the tip than the planar surfaces. Functionalizing the CFM tip by bonding octadecyl-hydrocarbon to it eliminated these surface chemical-CFM tip interactions and no differences in tip interaction with the sensillar surfaces were observed. Trichoid sensilla from the male antennae of a second species, Utethesia ornatrix, did not exhibit similar heterogeneity between ridge edges versus planar areas with regard to hydrogen bonding with the SiO₂ hydrophilic tip. Pores on U. ornatrix sensilla occurred only along the bases of ridges on their trichoid sensilla. We suggest that the surface lipids of the H. zea sensilla are distributed in a chemically heterogeneous fashion to aid adsorption and transport of aldehyde pheromone component molecules through the pores into the sensillum lumen, possibly through solubilization in an epicuticular lipid layer. The trichoid sensilla of U. ornatrix do not exhibit such surface chemical heterogeneity, and this species-difference may be due to the usage by U. ornatrix of hydrocarbon molecules rather than aldehydes for their sex pheromone components.     

Synthesis and structure–activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer’s disease

A series of thiazole derivatives were designed, and prepared to develop RAGE antagonist for the treatment of Alzheimer’s disease (AD). SAR studies were performed to optimize inhibitory activity on Aβ-RAGE binding. SAR studies showed that introducing an amino group at part A was essential for inhibitory activity on Aβ-RAGE binding. Compounds selected from Aβ-RAGE binding screening displayed inhibitory activity on Aβ transport across BBB. They also showed inhibitory activity against Aβ-induced NF-κB activation. These results indicated that our derivatives had a potential as therapeutic agent for the treatment of AD.     

The effect of laparoscopic surgery in stage II and III right-sided colon cancer: a retrospective study

Background

We examined the association of tumor-derived hepatocyte growth factor (HGF) with the clinicopathological features of gliomas and investigated the effect of HGF inhibition on the biological behavior of tumor cells in vitro in order to determine whether HGF is a valuable prognostic predictor for glioma patients.

Methods

Seventy-six cases of glioma were collected. The tumor-derived HGF expression, cell proliferation index (PI) and intratumoral microvessels were evaluated by immunohistochemistry. Correlation between immunostaining and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. U87MG glioma cells were transfected with short interference (si)-RNA for HGF, and the cell viability, migratory ability and chemosensitivity to cisplatin were evaluated in vitro.

Results

Both high HGF expression in tumor cells (59.2%, 45/76) and high PI were significantly associated with high-grade glioma and increased microvessels in tumors (P?<?0.05). However, only histological grading (P?=?0.004) and high-expression of HGF (P?=?0.008) emerged as independent prognostic factors for the overall survival of glioma patients. The tumor-derived HGF mRNA and protein expressions were significantly decreased in vitro after transfection of HGF siRNA. HGF siRNA inhibited the cell growth and reduced cell migratory ability. Moreover, HGF siRNA transfection enhanced the chemosensitivity of U87MG glioma cells to cisplatin.

Conclusion

This study indicated that there was significant correlation among tumor cell-derived HGF, cell proliferation and microvessel proliferation in gliomas. HGF might influence tumor progression by modulating the cell growth, migration and chemoresistance to drugs. Increased expression of HGF may be a valuable predictor for prognostic evaluation of glioma patients.     

Neural stimulation on human bone marrow‐derived mesenchymal stem cells by extremely low frequency electromagnetic fields

Adult stem cells are considered multipotent. Especially, human bone marrow‐derived mesenchymal stem cells (hBM‐MSCs) have the potential to differentiate into nerve type cells. Electromagnetic fields (EMFs) are widely distributed in the environment, and recently there have been many reports on the biological effects of EMFs. hBM‐MSCs are weak and sensitive pluripotent stem cells, therefore extremely low frequency‐electromagnetic fields (ELF‐EMFs) could be affect the changes of biological functions within the cells. In our experiments, ELF‐EMFs inhibited the growth of hBM‐MSCs in 12 days exposure. Their gene level was changed and expression of the neural stem cell marker like nestin was decreased but the neural cell markers like MAP2, NEUROD1, NF‐L, and Tau were induced. In immunofluorescence study, we confirmed the expression of each protein of neural cells. And also both oligodendrocyte and astrocyte related proteins like O4 and GFAP were expressed by ELF‐EMFs. We suggest that EMFs can induce neural differentiation in BM‐MSCs without any chemicals or differentiation factors. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012     

Electroantennogram responses of aphid nymphs to plant volatiles

Abstract. Electroantennogram (EAG) responses of immature aphids were investigated for 30 plant volatile compounds in third‐ and fourth‐stadium nymphs of the black bean aphid, Aphis fabae. The nymphs were destined to develop into adult alate (winged) virginoparae. The EAG response profiles were similar to those previously reported in the adults. Among the compounds tested, hexanonitrile elicited the largest EAG responses in both nymphal stadia, corresponding to previously reported results with adults. Six‐carbon aliphatic compounds showed relatively higher EAG activities in the nymphs but, in contrast, (E)‐2‐hexenal, benzaldehyde, α‐pinene and β‐pinene, and citronellal elicited relatively smaller EAG responses in nymphs than adults. Although overall EAG response profiles were similar between the third and the fourth stadia for the majority of the volatiles, four aldehyde compounds, hexanal (E)‐2‐heptenal, 2‐hydroxybenzaldehyde and citronellal, showed relatively higher EAG activities in the third than in the fourth stadium. The present study indicates that aphid nymphs possess a functional olfactory receptor system before the antennae are fully developed morphologically and physiologically.