Key Laboratory of Systems Bioengineering

Tianjin, China

Key Laboratory of Systems Bioengineering

Tianjin, China

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Xu S.,Tianjin University | Wang W.,CAS Tianjin Institute of Biomedical Engineering | Li X.,Tianjin Institute of Medical and Pharmaceutical Science | Liu J.,Tianjin University | And 3 more authors.
European Journal of Pharmaceutical Sciences | Year: 2014

As drug therapies become increasingly sophisticated, the synergistic benefits of two or more drugs are often required. In this study, we aimed at improving anti-tumor efficiency of paclitaxel (PTX)-incorporated thermo-sensitive injectable hydrogel by the synergy of burst release of doxorubicin hydrochloride (DOX·HCl). Thermosensitive injectable hydrogel composed of nanoparticles assembled from amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolaone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) was fabricated. Hydrophobic PTX and hydrophilic DOX·HCl were loaded simultaneously in the thermo-sensitive injectable hydrogel by a two-stage entrapment. Thermosensitive gelling behaviors of drug-loading PECT nanoparticle aqueous dispersions were studied. In vitro release profiles of PTX and DOX·HCl and in vivo anti-tumor effect by dual drugs from PECT hydrogel were investigated. The results showed that hydrophilic and hydrophobic drugs could be successfully entrapped in PECT hydrogel simultaneously without affecting its thermo-sensitive behavior. In vitro release profiles demonstrated the burst release of DOX·HCl and the sustained release of PTX. Anti-tumor effect was improved by a fast and tense attack caused by the burst release of hydrophilic DOX·HCl from hydrogel, which was continued by the sequent sustained release of PTX-incorporated nanoparticles and remnant DOX·HCl. Unintentionally, entrapped in PECT hydrogel, hydrophilic DOX·HCl was observed to have a sustained releasing pattern in vitro and in vivo. © 2014 Elsevier B.V. All rights reserved.


Jin H.,Tianjin University | Jin H.,Key Laboratory of Systems Bioengineering | Chen L.,Tianjin University | Chen L.,Key Laboratory of Systems Bioengineering | And 4 more authors.
Biotechnology Advances | Year: 2014

Large-scale production of renewable biofuels through microbiological processes has drawn significant attention in recent years, mostly due to the increasing concerns on the petroleum fuel shortages and the environmental consequences of the over-utilization of petroleum-based fuels. In addition to native biofuel-producing microbes that have been employed for biofuel production for decades, recent advances in metabolic engineering and synthetic biology have made it possible to produce biofuels in several non-native biofuel-producing microorganisms. Compared to native producers, these non-native systems carry the advantages of fast growth, simple nutrient requirements, readiness for genetic modifications, and even the capability to assimilate CO2 and solar energy, making them competitive alternative systems to further decrease the biofuel production cost. However, the tolerance of these non-native microorganisms to toxic biofuels is naturally low, which has restricted the potentials of their application for high-efficiency biofuel production. To address the issues, researches have been recently conducted to explore the biofuel tolerance mechanisms and to construct robust high-tolerance strains for non-native biofuel-producing microorganisms. In this review, we critically summarize the recent progress in this area, focusing on three popular non-native biofuel-producing systems, i.e. Escherichia coli, Lactobacillus and photosynthetic cyanobacteria. © 2014 Elsevier Inc.


Wang G.,Tianjin University | Huang D.,Tianjin University | Qi H.,Tianjin University | Wen J.,Tianjin University | And 4 more authors.
Bioresource Technology | Year: 2013

To rationally guide fumaric acid production improvement, metabolic profiling approach was performed to analyze metabolite changes of Rhizopus oryzae FM19 under different fermentation conditions. A correlation between the metabolic profiling and fumaric acid production was revealed by principal component analysis as well as partial least squares. Citric acid, oxaloacetic acid, 2-oxoglutarate, lactic acid, proline, alanine, valine, leucine were identified to be mainly responsible for the metabolism difference, which were involved in the Embden-Meyerhof-Parnas, tricarboxylic acid cycle, amino acid metabolism and fatty acid metabolism. Through the further analysis of metabolites changes together with the above pathways, exogenous addition strategies were developed, which resulted in 14% increase of fumaric acid (up to 56.5. g/L) and less by-products. These results demonstrated that metabolic profiling analysis could be successfully applied to the rational guidance of medium optimization and the productivity improvement of value-added compounds. © 2013 Elsevier Ltd.


Xu Q.,Nanjing University of Technology | Xu Q.,Tianjin University | Li S.,Nanjing University of Technology | Huang H.,Nanjing University of Technology | And 2 more authors.
Biotechnology Advances | Year: 2012

The growing concern about the safety of food and dairy additives and the increasing costs of petroleum-based chemicals have rekindled the interest in the fermentation processes for fumaric acid production. The key problems of the industrial production of microbial fumaric acid are reviewed in this paper. Various strategies, including strain improvement, morphology control, substrate choice, fermentation process and separation process, are summarized and compared, and their economical possibilities for industrial processes are discussed. The market prospects and technological strategies for value-added fumaric acid derivatives are also addressed. The future prospects of microbial fumaric acid production are proposed at the end of this article. © 2012 Elsevier Inc.


Yu S.,Tianjin University | Huang D.,Tianjin University | Wen J.,Tianjin University | Wen J.,Key Laboratory of Systems Bioengineering | And 4 more authors.
Bioresource Technology | Year: 2012

Femtosecond laser irradiation was employed to induce mutations in Rhizopus oryzae, leading to increases in fumaric acid production. Compared to the parental strain, mutant strain FM19 exhibited an increase in titer and yield of 56.3% and 36.6%, respectively, corresponding to a titer of 49.4. g/L and a yield of 0.56. g fumaric acid per g glucose. Metabolic profiling by gas chromatography-mass spectrometry revealed that higher levels of carbon (Embden-Meyerhof-Parnas and tricarboxylic acid cycle) and amino acid metabolism were operating in the high-yielding strain; particularly, 4-aminobutyric acid and 5-aminolevulinic acid were increased 10.33- and 7.22-fold, respectively, compared with parental strain during stationary phase. These findings provided new insights into metabolic characterization of high-yielding fumaric acid R. oryzae. © 2012 Elsevier Ltd.


Wang J.,Tianjin University | Wang J.,Key Laboratory of Systems Bioengineering | Wu G.,University of Maryland Baltimore County | Chen L.,Tianjin University | And 3 more authors.
BMC Genomics | Year: 2013

Background: As one of the most dominant bacterial groups on Earth, cyanobacteria play a pivotal role in the global carbon cycling and the Earth atmosphere composition. Understanding their molecular responses to environmental perturbations has important scientific and environmental values. Since important biological processes or networks are often evolutionarily conserved, the cross-species transcriptional network analysis offers a useful strategy to decipher conserved and species-specific transcriptional mechanisms that cells utilize to deal with various biotic and abiotic disturbances, and it will eventually lead to a better understanding of associated adaptation and regulatory networks.Results: In this study, the Weighted Gene Co-expression Network Analysis (WGCNA) approach was used to establish transcriptional networks for four important cyanobacteria species under metal stress, including iron depletion and high copper conditions. Cross-species network comparison led to discovery of several core response modules and genes possibly essential to metal stress, as well as species-specific hub genes for metal stresses in different cyanobacteria species, shedding light on survival strategies of cyanobacteria responding to different environmental perturbations.Conclusions: The WGCNA analysis demonstrated that the application of cross-species transcriptional network analysis will lead to novel insights to molecular response to environmental changes which will otherwise not be achieved by analyzing data from a single species. © 2013 Wang et al.; licensee BioMed Central Ltd.


Zhong C.,Tianjin University | Cao Y.-X.,Tianjin University | Li B.-Z.,Tianjin University | Yuan Y.-J.,Tianjin University | Yuan Y.-J.,Key Laboratory of Systems Bioengineering
Biofuels, Bioproducts and Biorefining | Year: 2010

Energy security and environmental stress force China to seek and develop biofuels as a substitute of fossil energy. Meanwhile, China has great potential to provide a large quantity of feedstocks for biofuel production due to its vast amount of non-food crops, such as tuberous crops, sweet sorghum, cellulosic biomass, and algae. Recently, the study and the industrial-scale production of biofuels, particularly, fuel ethanol and biodiesel, have progressed remarkably in China as a result of government preferential policies and funding supports. We have briefly reviewed the historical development of biofuels in China with special emphasis on current feedstock utilization and process technology development. The bottlenecks of utilizing various feedstocks have also been analyzed and the prospects for future biofuel development in China have been explored. Biorefineries integrating reliable, low-cost and sufficient non-food feedstock supplies with highly efficient, environmentally friendly process technologies could sustain a bright future for biofuel development in China. © 2010 Society of Chemical Industry and John Wiley & Sons, Ltd.


Liu J.,Tianjin University | Liu J.,Key Laboratory of Systems Bioengineering | Chen L.,Tianjin University | Chen L.,Key Laboratory of Systems Bioengineering | And 6 more authors.
Biotechnology for Biofuels | Year: 2012

Background: Recent studies have demonstrated that photosynthetic cyanobacteria could be an excellent cell factory to produce renewable biofuels and chemicals due to their capability to utilize solar energy and CO 2 as the sole energy and carbon sources. Biosynthesis of carbon-neutral biofuel alkanes with good chemical and physical properties has been proposed. However, to make the process economically feasible, one major hurdle to improve the low cell tolerance to alkanes needed to be overcome. Results: Towards the goal to develop robust and high-alkane-tolerant hosts, in this study, the responses of model cyanobacterial Synechocystis PCC 6803 to hexane, a representative of alkane, were investigated using a quantitative proteomics approach with iTRAQ - LC-MS/MS technologies. In total, 1,492 unique proteins were identified, representing about 42% of all predicted protein in the Synechocystis genome. Among all proteins identified, a total of 164 and 77 proteins were found up- and down-regulated, respectively. Functional annotation and KEGG pathway enrichment analyses showed that common stress responses were induced by hexane in Synechocystis. Notably, a large number of transporters and membrane-bound proteins, proteins against oxidative stress and proteins related to sulfur relay system and photosynthesis were induced, suggesting that they are possibly the major protection mechanisms against hexane toxicity. Conclusion: The study provided the first comprehensive view of the complicated molecular mechanism employed by cyanobacterial model species, Synechocystis to defend against hexane stress. The study also provided a list of potential targets to engineer Synechocystis against hexane stress. © 2012 Lui et al.; licensee BioMed Central Ltd.


Yao Y.-F.,Key Laboratory of Systems Bioengineering | Wang C.-S.,Key Laboratory of Systems Bioengineering | Qiao J.,Key Laboratory of Systems Bioengineering | Zhao G.-R.,Key Laboratory of Systems Bioengineering
Metabolic Engineering | Year: 2013

Salvianic acid A, a valuable derivative from L-tyrosine biosynthetic pathway of the herbal plant Salvia miltiorrhiza, is well known for its antioxidant activities and efficacious therapeutic potential on cardiovascular diseases. Salvianic acid A was traditionally isolated from plant root or synthesized by chemical methods, both of which had low efficiency. Herein, we developed an unprecedented artificial biosynthetic pathway of salvianic acid A in E. coli, enabling its production from glucose directly. In this pathway, 4-hydroxyphenylpyruvate was converted to salvianic acid A via D-lactate dehydrogenase (encoding by d-ldh from Lactobacillus pentosus) and hydroxylase complex (encoding by hpaBC from E. coli). Furthermore, we optimized the pathway by a modular engineering approach and deleting genes involved in the regulatory and competing pathways. The metabolically engineered E. coli strain achieved high productivity of salvianic acid A (7.1. g/L) with a yield of 0.47. mol/mol glucose. © 2013 Elsevier Inc.


Li B.-Z.,Key Laboratory of Systems Bioengineering | Balan V.,Michigan State University | Yuan Y.-J.,Key Laboratory of Systems Bioengineering | Dale B.E.,Michigan State University
Bioresource Technology | Year: 2010

With growing demand for bio-based fuels and chemicals, there has been much attention given to the performance of different feedstocks. We have optimized the ammonia fiber expansion (AFEX) pretreatment and fermentation process to convert forage and sweet sorghum bagasse to ethanol. AFEX pretreatment was optimized for forage sorghum and sweet sorghum bagasse. Supplementing xylanase with cellulase during enzymatic hydrolysis increased both glucan and xylan conversion to 90% at 1% glucan loading. High solid loading hydrolyzates from the optimized AFEX conditions were fermented using Saccharomyces cerevisiae 424A (LNH-ST) without any external nutrient supplementation or detoxification. The strain was better able to utilize xylose at pH 6.0 than at pH 4.8, but glycerol production was higher for the former pH than the latter. The maximum final ethanol concentration in the fermentation broth was 30.9 g/L (forage sorghum) and 42.3 g/L (sweet sorghum bagasse). A complete mass balance for the process is given. © 2009 Elsevier Ltd. All rights reserved.

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