Integrating systematic biological and proteomics strategies to explore the pharmacological mechanism of danshen yin modified on atherosclerosis.

This research utilized the systematic biological and proteomics strategies to explore the regulatory mechanism of Danshen Yin Modified (DSYM) on atherosclerosis (AS) biological network. The traditional Chinese medicine database and HPLC was used to find the active compounds of DSYM, Pharmmapper database was used to predict potential targets, and OMIM database and GeneCards database were used to collect AS targets. String database was utilized to obtain the other protein of proteomics proteins and the protein-protein interaction (PPI) data of DSYM targets, AS genes, proteomics proteins and other proteins. The Cytoscape 3.7.1 software was utilized to construct and analyse the network. The DAVID database is used to discover the biological processes and signalling pathways that these proteins aggregate. Finally, animal experiments and proteomics analysis were used to further verify the prediction results. The results showed that 140 active compounds, 405 DSYM targets and 590 AS genes were obtained, and 51 differentially expressed proteins were identified in the DSYM-treated ApoE-/- mouse AS model. A total of 4 major networks and a number of their derivative networks were constructed and analysed. The prediction results showed that DSYM can regulate AS-related biological processes and signalling pathways. Animal experiments have also shown that DSYM has a therapeutic effect on ApoE-/-mouse AS model (P < .05). Therefore, this study proposed a new method based on systems biology, proteomics, and experimental pharmacology, and analysed the pharmacological mechanism of DSYM. DSYM may achieve therapeutic effects by regulating AS-related signalling pathways and biological processes found in this research.

Taxa hold little information about organisms: Some inferential problems in biological systematics.

The taxa that appear in biological classifications are commonly seen as representing information about the traits of their member organisms. This paper examines in what way taxa feature in the storage and retrieval of such information. I will argue that taxa do not actually store much information about the traits of their member organisms. Rather, I want to suggest, taxa should be understood as functioning to localize organisms in the genealogical network of life on Earth. Taxa store information about where organisms are localized in the network, which is important background information when it comes to establishing knowledge about organismal traits, but it is not itself information about these traits. The view of species and higher taxa that is proposed here follows from examining three problems that occur in contemporary biological systematics and are discussed here: the problem of generalization over taxa, the problem of phylogenetic inference, and the problematic nature of the Tree of Life.

Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Advances on systems metabolic engineering of Bacillus subtilis as a chassis cell.

The Gram-positive model bacterium Bacillus subtilis, has been broadly applied in various fields because of its low pathogenicity and strong protein secretion ability, as well as its well-developed fermentation technology. B. subtilis is considered as an attractive host in the field of metabolic engineering, in particular for protein expression and secretion, so it has been well studied and applied in genetic engineering. In this review, we discussed why B. subtilis is a good chassis cell for metabolic engineering. We also summarized the latest research progress in systematic biology, synthetic biology and evolution-based engineering of B. subtilis, and showed systemic metabolic engineering expedite the harnessing B. subtilis for bioproduction.

Systematic biological and proteomics strategies to explore the regulation mechanism of Shoutai Wan on recurrent spontaneous Abortion's biological network.

ETHNOPHARMACOLOGICAL RELEVANCE: Shoutai Wan (STW) is a classic herbal formula for the treatment of recurrent spontaneous abortion (RSA), and clinical studies have shown the effectiveness of STW on RSA. However, the molecular mechanism of STW treatment of RSA is still unclear. METHODS: (1) Animal experiments: The normal pregnancy model was established with CBA/J*BALB/C, and the RSA model was established by CBA/J*DBA/2. The RSA model CBA/J*DBA/2 pregnant mice were randomly divided into four groups (RSA model group, STW low, medium and high dose groups) according to the order of pregnancy, respectively. The drug administration starts from the first day of pregnancy to the 14th day of pregnancy. The embryo loss rate (ELR) of each group was calculated. (2) Proteomic analysis of decidual tissue: The total protein of decidual tissue of each group was isolated by solid phase pH gradient 2-DE technique. The differentially expressed protein spots were analyzed and identified by PDQuest images; the peptide quality fingerprinting (PMF) was obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Then, the proteins were identified by Mascot software searching, their functions were identified by bioinformatics strategy. (3) The expression of HSP27, α-enolase and Transferrin was detected by Western blotting and the expression of Annexin A2 and Transferrin was detected by immunohistochemistry. (4) The differential proteins and potential targets were analyzed by systematic biological strategy. RESULTS: (1) Compared with the normal group, the ELR in the RSA model group was significantly higher (P < 0.01). Compared with the model group, the ELR in the STW high, medium dose groups was lower (P < 0.01). (2) A 2-DE map of the decidual tissue of the RSA model group, normal pregnancy group, STW low, medium and high dose groups was established. Thirty proteins were identified. (3) The results of western blot showed that the expression of HSP27 and a-enolase in the RSA model group was higher than that in the normal group, and the expression of transferrin was lower (P < 0.01). Compared with the model group, the expression of HSP27 and a-enolase in STW high, medium dose groups was decreased (P < 0.01); Compared with the model group, the expression of Transferrin in the STW high dose group was increased (P < 0.01). (5) A lot of RSA treatment-related targets, biological processes and pathways were found after the systematic biological analysis. CONCLUSION: (1) STW may reduce the ELR of the RSA mice. (2) The results of proteomics suggest that RSA is a complex process involving multiple proteins. STW can regulate the expression of various proteins in the decidual tissue of RSA mice, suggesting that it can act on multiple targets. (3) The results of western blotting of HSP27, a-enolase, transferrin were consistent with the results of proteomic analysis. (4) STW may achieve therapeutic effects by interfering with the targets, biological processes and signaling pathways discovered in this study.

Decentralized but Globally Coordinated Biodiversity Data.

Centralized biodiversity data aggregation is too often failing societal needs due to pervasive and systemic data quality deficiencies. We argue for a novel approach that embodies the spirit of the Web ("small pieces loosely joined") through the decentralized coordination of data across scientific languages and communities. The upfront cost of decentralization can be offset by the long-term benefit of achieving sustained expert engagement, higher-quality data products, and ultimately more societal impact for biodiversity data. Our decentralized approach encourages the emergence and evolution of multiple self-identifying communities of practice that are regionally, taxonomically, or institutionally localized. Each community is empowered to control the social and informational design and versioning of their local data infrastructures and signals. With no single aggregator to exert centralized control over biodiversity data, decentralization generates loosely connected networks of mid-level aggregators. Global coordination is nevertheless feasible through automatable data sharing agreements that enable efficient propagation and translation of biodiversity data across communities. The decentralized model also poses novel integration challenges, among which the explicit and continuous articulation of conflicting systematic classifications and phylogenies remain the most challenging. We discuss the development of available solutions, challenges, and outline next steps: the global effort of coordination should focus on developing shared languages for data signal translation, as opposed to homogenizing the data signal itself.

Transferrin Functionization Elevates Transcytosis of Nanogranules across Epithelium by Triggering Polarity-Associated Transport Flow and Positive Cellular Feedback Loop.

Overcoming the epithelial barriers to enhance drug transport is a focused topic for gastrointestinal, intratracheal, intranasal, vaginal, and intrauterine delivery. Nanomedicines with targeting functionization promote such a process owing to specific ligand-receptor interaction. However, compared to the cell uptake of targeting nanotherapies, currently few studies concentrate on their transcytosis including endocytosis for "in" and exocytosis for "out". In fact, the cellular regulatory mechanism for these pathways as well as the principle of ligand's effect on the transcytosis are almost ignored. Here, we fabricated transferrin (Tf) functionalized nanogranules (Tf-NG) as the nanomedicine model and confirmed the difference in polar distributions of Tf receptors (TfRs) between two epithelium models (bipolarity for Caco-2 and unipolarity for MDCK cells). Compared to the nonspecific reference, Tf-conjugation boosted the endocytosis by different pathways in two cell models and transformed the intracellular route of Tf-NG in both cells differently, affecting exocytosis, recycling, and degradation but not the secretion pathway. Only bipolar cells could establish a complete transport flow from "in" to "out", leading to the enhanced transcytosis of Tf-NG. Importantly, epithelia could make responses to Tf-NG transcytosis. Based on the quantitative proteomics, the intracellular trafficking of Tf-NG altered the protein expression profiles, in which the endocytosis- and transcytosis-related proteins were specifically upregulated. Particularly, only bipolar cells could positively feed back to such trafficking via accelerating the subsequent Tf-NG transcytosis. Here, all the cell transport of Tf-NG was polarity associated. In summary, Tf modification elevated the transcytosis of Tf-NG across the epithelium by triggering the polarity-associated transport flow and positive cell feedback loop. These findings provided an insight into the targeting nanodelivery for efficient transport through epithelial barriers.

Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Investigating the regulation mechanism of baicalin on triple negative breast cancer's biological network by a systematic biological strategy.

OBJECTIVE: To investigate the regulation mechanism of baicalin on triple negative breast cancer (TNBC)'s biological network by a systematic biological strategy and cytology experiment. METHODS: A systematic biological methodology is utilized to predict the potential targets of baicalin, collect the genes of TNBC, and analyze the TNBC and baicalin's network. After the systematic biological analysis is performed, the cytology experiment, real-time quantitative PCR (qPCR) is used to validate the key biological processes and signaling pathways. RESULTS: After systematic biological analysis, two networks were constructed and analyzed: (1) TNBC network; (2) Baicalin-TNBC protein-protein interaction (PPI) network. Several TNBC-related, treatment-related targets, clusters, signaling pathways and biological processes were found. Cytology experiment shows that baicalin can inhibit the proliferation, migration and invasion of breast cancer MDA-MB-231 cells in vitro (P < 0.05). The results of qPCR showed that baicalin increase the expression of E-cadherin mRNA, and decrease the expression of vimentin, ß-catenin, c-Myc and MMP-7 mRNA in LPS-induced breast cancer MDA-MB-231 cells (P < 0.05). CONCLUSION: Baicalin may achieve anti-tumor effects through regulating the targets, biological processes and pathways found in this research.

Systematic identification of the druggable interactions between human protein kinases and naturally occurring compounds in endometriosis.

Diverse kinase signaling pathways have been involved in the pathogenesis of endometriosis (EM), which can be modulated either by directly targeting the hub kinases or by indirectly regulating marginal members in the pathways. Here, a systematic kinase-inhibitor interaction profile was created for 8 naturally occurring compounds against 20 human protein kinases. The compounds are all non-sterid that have been reported as pharmacologically active molecular entities potential for EM therapeutics, while the kinases were curated via gene ontology terms enriched from the gene co-citation network with EM. The resulting profile was analyzed at structural, energetic and dynamic levels to identify druggable kinase-compound interactions. The compounds Gossypol, Curcumin and EGCG showed a similar interaction profile across these kinases; they can bind tightly to the top-listed kinases in gene ontology, while the compounds Marrubiin, Apigenin and DIM were predicted to exhibit generally weak affinity for the 20 curated kinases. The JNK kinase, a MAPK family member, was identified as a putative candidate of druggable target for EM therapeutics; the inhibitory activity of eight naturally occurring compounds as well as a sophisticated kinase inhibitor SP600125 against the JNK was tested using enzymatic activity analysis. As might be expected, the Gossypol and EGCG were determined to have high inhibitory activity at namomolar level (IC50=55 and 94nM, respectively), which are comparable with or better than the positive control SP600125 (IC50=76nM), while other tested compounds exhibited weak inhibition (IC50>100nM) or bad potency (IC50=n.d.) against the kinase.

Entomological journals and publishing in Japan.

Here I present an overview of entomological journals and publishing in Japan, thereby providing a convenient portal to the valuable scientific resources for the world's entomological researchers and scientific communities. Currently, except for several international journals published fully in English such as Applied Entomology and Zoology and Entomological Science, many entomological and entomology-related journals in Japan are not indexed by major scientific databases like Web of Science, and therefore they are neither conveniently recognizable nor accessible for the world's entomological communities. However, I point out that many of the contents of such journals are freely available via Japan's public platforms for electronic scientific literature, Japan Science and Technology Information Aggregator, Electronic (J-stage) or Citation Information by National Institute of Informatics (CiNii). Here I list 32 entomological and entomology-related societies and their 45 journals, the majority of which belong to either the Union of Japanese Societies for Insect Sciences (UJSIS), the Union of the Japanese Societies for Systematic Biology (UJSSB), the Union of Japanese Societies for Natural History (UJSNH), or the Union of Japanese Societies for Biological Science (UJSBS), with their respective URL and open-access availability.

Application of systematic biology technology in research of traditional Chinese medicine based on overall research / 中草药

Traditional Chinese medicine is the treasure of China, which has played an indelible role in the process of fighting against diseases. Under the background of times of building Healthy China, how to play the unique advantages of traditional Chinese medicine in the disease prevention and treatment is the focus of attention. Traditional Chinese medicine has the characteristics of "multi-component, multi-target, and overall regulation", and it's not enough to reveal its internal essence only by the way of "local concept", so the research thinking of "overall concept"is imperative. System biology, a research technology, which understands the organism from a holistic perspective and coincides with the way of "overall concept"of traditional Chinese medicine. Therefore, the research strategy of traditional Chinese medicine based on system biology with highly feasible. In this paper, the application of system biology technologies, such as genomics, transcriptome, proteomics, metabonomics, microbiomics, omics combination and network pharmacology technology, in the research of ingredients, pharmacology and toxicology, identification, cultivation and genetic breeding of traditional Chinese medicine was reviewed, in order to provide reference for the further application of system biology strategy in the research of traditional Chinese medicine, based on the idea of "overall concept".

High content screening analysis for systematic study on traditional Chinese medicine / 中草药

High content screening(HCS) analysis is an advanced technique in the era of systematic biology,which can comprehensively reflect the changes of cell with live,dynamic,and multiparametric characters.It is a good tool to study the complex ingredients and mechanism of traditional Chinese medicine(TCM).Application of the technique would contribute to the discovery of effective ingredients,elucidation of mechanism,and development of TCM theory.