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The activation of artemisinin and its derivatives (ARTs) to generate ROS and other free radicals is mainly heme- or ferrous iron-dependent. ARTs induce ferroptosis in tumor cells, although the involvement of ferroptosis in malaria remains unclear. We found that three typical inducers of ferroptosis (erastin, RSL3 and sorafenib) could effectively mimic DHA inhibition on the growth of blood-stage parasites, which exhibited synergistic or nearly additive interactions in vitro with DHA, while the combination of DHA with ferroptosis inhibitors (deferoxamine, liproxstatin-1) had an obvious antagonistic effect. DHA, similar to ferroptosis inducers, can simultaneously induce the accumulation of ferroptosis-associated cellular labile iron and lipid peroxide. However, deferoxamine and liproxstatin-1 reduced the increase in ferrous iron and lipid peroxide caused by DHA. These results suggested that ferroptosis might be an effective way to induce cell death in parasites and could be a primary mechanism by which DHA kills parasites, with almost 50% contribution at low concentrations. These results provide a new strategy for antimalarial drug screening and clinical medication guidance.

Cellulose-based materials are vulnerable to moisture and microorganisms and thus lose their original mechanical properties and durability; meanwhile, self-cleaning technique as a disruptive nanotechnology of waterproofing is attracting tremendous interest. Here, we develop a facile, cheap, and scalable “top-down” strategy to fabricate a transparent self-cleaning surface for cellulose-based materials by spray-coating a stable emulsion of nano-SiO2 particles. The nanoparticles are precisely synthesized at an average diameter of ∼110 nm via a sol–gel way and finely tailored with hydrophobic function by successive modification of poly(dimethylsiloxane) (PDMS) and (heptadecafluoro-1,1,2,2-tetradecyl)trimethoxysilane (17F). The modified nano-SiO2 particles well-distributed on the microscale rough surface of the cellulose-based materials by spray-coating to form a micro/nano two-tier structure to entrap air for water resistance, and thus build a superhydrophobic surface with static water contact angle (WCA) over...

Artemisinin and its analogues (ARTs) are currently the most effective anti-malarial drugs, but the precise mechanism of action is still highly controversial. Effects of ARTs on

Green bamboo was hydrolyzed over a range of durations at different temperatures. A simple pseudo-homogeneous irreversible first order kinetic model was developed to describe pentosan solubility during steam treatment of green bamboo. To avoid the influence of soluble pentosan during heating process, kinetic parameters were effectively dissolved based on the data in the reacting process. Moreover, the pentosan solubility during heating process was also well modeled by numerical algorithm method. According to the origin of H factor, a modified parameter called steam treatment factor (f(P)) was proposed in this paper based on the determined kinetic constants. Finally, residual pentosan in whole process could be predicted properly based on the f(P) and the introducing of potential hydrolysis degree (h(d)). After using f(P) to combine reaction temperature and time into a single factor, comparative result showed that steam treatment is more effective for removing pentosan compared with hot water extraction. (C) 2012 Elsevier Ltd. All rights reserved.

Cinnamaldehyde was shown to have significant anti-inflammatory and anti-pyretic actions in studies from both others' and our lab. Prostaglandin E2 (PGE2) plays a key role in generation of these pathological states, while PGE, synthase-1 (mPGES-1) is one of crucial biological elements in the process of PGE2 production. And as a downstream inducible terminal prostaglandin synthase of COX-2, mPGES-1 is now regarded as a more promising novel drug target than COX-2 and is attracting more and more attention from both academia and pharmaceutical industry. The purpose of present study was to further investigate the anti-inflammatory and antipyretic molecular mechanisms of cinnamaldehyde based on the mouse macrophage cell line RAW264. 7 in vitro. The PGE2 was identified by using the method of enzyme-linked immunosorbent assay (ELISA) and the expression of COX-2 and mPGES-1 at mRNA and protein levels was detected by the Real-time PCR and Western blotting methods respectively. The experimental results suggested that cinnamaldehyde could evidently reverse the increased production of PGE2induced by IL-1beta. Moreover, the up-regulated expression levels of mPGES-1 and COX-2 were significatly decreased. Together, these results provide compelling evidence that the down-regulated actions to both the production of PGE2 as well as the expression of mPGES-I might account for, at least in part, the anti-inflammatory and anti-pyretic effects of cinnamaldehyde.

The emergence and spread of multidrug-resistant strains of Mycobacterium tuberculosis represent an increasing public health problem. Understanding multidrug-resistant mechanism(s) is essential for efficient treatment and control of tuberculosis. Mutations in gene rpsL, encoding the ribosomal protein S12, are responsible for most of the high-level Streptomycin resistance in Mycobacterium tuberculosis. Recently, a mass of data about gene rpsL continue to accumulate rapidly, but it is lack for systemic analysis using these data. Here, we used bioinformatics tools to analyze globe data about the rpsL of Mycobacterium tuberculosis. Phylogenetic analysis showed that the rpsL and its homologs were clearly divided into three groups, but they are all from organisms known as tuberculosis pathogens, which implied that general conformational structure of the rpsL did not change. Structure analysis showed that the 43 region of the rpsL alter hydrophilic nature in the wild-type rpsL to hydrophobic nature in the mutation. Prediction of the secondary structure of ribosomal protein S12 displayed a coil within the helix structure of the 43 region in the wild-type rpsL whereas just helix structure in the mutation. Therefore, it was suggested that mutations of hydrophilic nature and coil within the helix structure of the 43 region of gene rpsL are responsible for most of the high-level Streptomycin resistance in Mycobacterium tuberculosis.

BACKGROUND: Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. METHODOLOGY: We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. CONCLUSIONS: This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking.