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In recent years, nanodrug delivery systems have attracted increasing attention due to their advantages, such as high drug loading, low toxicity and side effects, improved bioavailability, long circulation time, good targeting and controlled drug release efficiency. Self-assembly technology has developed rapidly in recent decades and plays an important role in the research and development of nanoscience. The combination of nanometer drug delivery and self-assembly technology can realize the self-delivery process of drugs. The facile synthesis process and strong biological affinity can both effectively enhance the therapeutic efficacy and reduce the toxicity of drugs. This combination of technologies has received wide attention in the field of nanobiomedicine. In this review, we summarize the research progress and applications of different types of self-assembled nanodrug delivery systems (amphiphilic block copolymer-based self-assembled drug delivery system, carrier-free nanodrugs, peptide-based self-assembled delivery system, metal-polyphenol self-assembly and natural small-molecule self-assembled nanodrug delivery systems), which are expected to have potential therapeutic value in the field of biomedicine in the future.

Traditional Chinese medicines (TCMs) have wide pharmacological activities, and the ingredients in individual TCMs determine their efficacies. To understand the "efficacy-nature-structure" relationship of TCM, compounds from 2444 kinds of herbs were collected, and the associations between family, structure, nature, and biological activities were mined and analyzed. Bernoulli Naïve Bayes profiling and a data analysis method were used to predict the targets of compounds. The results show that genetic material determined the representation of ingredients from herbs and the nature of TCMs and that the superior scaffolds of compounds of cold nature were 2-phenylochrotinone, anthraquinone, and coumarin, while the compounds of hot nature were cyclohexene. The results of the similarity analysis and distribution for molecular descriptors of compounds show that compounds associated with the same nature were similar and compounds associated with different natures occurred as a transition in part. As for integral compounds from 2-phenylochrotinone, anthraquinone, coumarin, and cyclohexene, the value of the shape index increased, indicating the transition of scaffolds from a spherical structure to a linear structure, with various molecular descriptors decreasing. Three medicines and three recipes prescribed based on "efficacy-nature-structure" had a higher survival rate in the clinic and provided powerful evidence for TCM principles. The research improves the understanding of the "efficacy-nature-structure" relationship and extends TCM applications.

The theory of cold–hot nature of Chinese herbal medicines (CHMs) is the core theory of CHM. It has been found that the volatile oil ingredients in CHMs are closely related to their cold–hot nature. Guided by the scientific hypothesis that “CHMs with similar component substances should have similar medicinal natures”, exploration of the intelligent identification of the cold–hot nature of CHMs based on the similarity of their volatile oil ingredients has become a research focus. Gas chromatography (GC) chemical fingerprints have been widely used in the separation of volatile oil ingredients to analyze the cold–hot nature of CHMs. To verify the above hypothesis, in this work, we study the quantification of the similarity of the volatile oil ingredients of CHMs to their fingerprint similarity and explore the relationship between the volatile oil ingredients of CHMs and their cold–hot nature. In this study, we utilize GC technology to analyze the chemical ingredients of 61 CHMs that have a clear cold–hot nature (including 30 ‘cold’ CHMs and 31 ‘hot’ CHMs). Using the constructed fingerprint dataset of CHMs, a distance metric learning algorithm is applied to measure the similarity of the GC fingerprints. Furthermore, an improved k-nearest neighbor (kNN) algorithm is proposed to build a predictive identification model to identify the cold–hot nature of CHMs. The experimental results prove our inference that CHMs with similar component substances should have similar medicinal natures. Compared with existing classical models, the proposed identification scheme has better predictive performance. The proposed prediction model is proved to be effective and feasible.

Marine green algae are valuable sources of diverse health-promoting bioactive components. Ulvan is suitable for biological applications due to its unique structure and numerous bioactivities. Here, the complex structure of ulvan from Ulva pertusa was analyzed using specific ulvan lyase degradation, MS, and NMR detection. Its structure mainly consists of →4)-β-d-GlcA-(1 → 4)-α-l-Rha3S-(1 → and →4)-β-d-Xyl-(1 → 4)-α-l-Rha3S-(1 → repeating units. Small amounts of →4)-α-l-IdoA-(1 → 4)-α-l-Rha3S-(1 → unit also exist. In addition, a minor number of branches, a single GlcA, and a long branch containing GlcA-Glc were linked to Rha3S. The antiviral activity of the ulvan and its degraded fragments were further investigated. Ulvan (1068.2 kDa) and ulvan-F1 (38.5 kDa) with relatively high molecular weight showed potency of inhibiting the infection and replication of vesicular stomatitis virus (VSV) at 100 μg/mL, the inhibition rate of VSV replication was 40.75% and 40.13%, respectively. These results indicated that ulvan has potential as a functional agent.

Suaeda salsa L. (Chenopodiaceae) is a wild vegetable distributed along the northern coast of China. Searching for potential agents with health benefits from S. salsa L. led to the identification of 14 flavonoids (1-14), eight phenolic acids (15-22), one coumarin (23), one benzoquinone (24), two sesquiterpenes (25, 26), and three lignins (27-29) from an aqueous ethanol (EtOH) extract of the above-ground whole plant using various column chromatographic methods. High-resolution electrospray ionization mass spectrometry (HRESIMS) analyses and nuclear magnetic resonance (

Platycodin D (PD) is a naturally occurring, biologically active triterpenoid saponin isolated from a medicinal food homology plant called Platycodon grandiflorus (Jacq.) A. DC. It is involved in the processing of various biological activities. While investigating the anti-inflammatory property of PD using lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells, we unexpectedly found that PD exhibited toxicity to RAW 264.7 cells. In this study, the toxic effect of PD on RAW 264.7 cells was systematically evaluated for the first time. The results showed that PD (12.5−200 µM) significantly reduced cell viability and inhibited cell proliferation in a dose-dependent manner. At a concentration of 20 µM, PD significantly increased lactate dehydrogenase activity and the mRNA and protein expression of Bax, p53, Casp3, IL-1β, and TNF-α. Interestingly, PD (0.8−20 µM) inhibited the expression of inflammatory cytokines in LPS-stimulated RAW 264.7 cells. PD (20 µM) also significantly increased reactive oxygen species (ROS) levels and the expression of oxidative stress-related genes and proteins. This study revealed that PD exhibited immunotoxicity to RAW 264.7 cells, with possible mechanisms including oxidative stress-mediated apoptosis resulting in activation of the mitochondrial apoptosis pathway and dysregulated expression of inflammatory cytokines. This study evaluated the impact of PD on immunity and provided guidelines for its future biological application.

Although the middle temporal gyrus (MTG) has been parcellated into subregions with distinguished anatomical connectivity patterns, whether the structural topography of MTG can inform functional segregations of this area remains largely unknown. Accumulating evidence suggests that the brain's underlying organization and function can be directly and effectively delineated with resting‐state functional connectivity (RSFC) by identifying putative functional boundaries between cortical areas. Here, RSFC profiles were used to explore functional segregations of the MTG and defined four subregions from anterior to posterior in two independent datasets, which showed a similar pattern with MTG parcellation scheme obtained using anatomical connectivity. The functional segregations of MTG were further supported by whole brain RSFC, coactivation, and specific RFSC, and coactivation mapping. Furthermore, the fingerprint with predefined 10 networks and functional characterizations of each subregion using meta‐analysis also identified functional distinction between subregions. The specific connectivity analysis and functional characterization indicated that the bilateral most anterior subregions mainly participated in social cognition and semantic processing; the ventral middle subregions were involved in social cognition in left hemisphere and auditory processing in right hemisphere; the bilateral ventro‐posterior subregions participated in action observation, whereas the left subregion was also involved in semantic processing; both of the dorsal subregions in superior temporal sulcus were involved in language, social cognition, and auditory processing. Taken together, our findings demonstrated MTG sharing similar structural and functional topographies and provide more detailed information about the functional organization of the MTG, which may facilitate future clinical and cognitive research on this area.

Public health safety issues have been plaguing the world since the pandemic outbreak of coronavirus disease (COVID-19). However, most personal protective equipments (PPE) do not have antibacterial and anti- toxicity effects. In this work, we designed and prepared a reusable, antibacterial and anti-toxicity Polyacrylonitrile (PAN) based nanofibrous membrane cooperated with Ag/g-C

Background and objectives Bone age assessment (BAA) is widely used in determination of discrepancy between skeletal age and chronological age. Manual approaches are complicated which require experienced experts, while existing automatic approaches are perplexed with small and imbalanced samples which is a big challenge in deep learning. Methods In this study, we proposed a new deep learning based method to improve the BAA training in both pre-training and training architecture. In pre-training, we proposed a framework using a new distance metric of cosine distance in the framework of optimal transport for data augmentation (CNN-GAN-OTD). In the training architecture, we explored the order of gender label and bone age information, supervised and semi-supervised training. Results We found that the training architecture with the CNN-GAN-OTD based data augmentation and supervised gender-last classification with supervised Inception v3 network yielded the best assessment (mean average error of 4.23 months). Conclusions The proposed data augmentation framework could be a potential built-in component of general deep learning networks and the training strategy with different label order could inspire more and deeper consideration of label priority in multi-label tasks.

Background The nature of Chinese herbal medicines (CHMs) is a bridge between traditional Chinese medicine and clinical application. Accurate nature identification of CHMs is essential for guiding the clinical application of CHMs. Objective To develop a new method for nature identification of CHMs according to compounds in CHMs. Methods The nature of a CHM is a comprehensive manifestation of the properties of various compounds in the CHM. In this study, 2012 CHM compounds were extracted to construct a compound data set. Molecular descriptors were utilized to build an identification model for classification of the cold-hot-neutral nature of CHM compounds. Results The predictive accuracy and confusion matrix were validated using the assembled data set. The best model produced accuracies of 96.5 ± 0.5% and 86.5 ± 1.5% on training set and test set, respectively. Furthermore, the identification model is robust in predicting the cold-hot-neutral nature of CHM compounds. Conclusion This work shows how a classification model for medical nature identification can be developed. The derived model can be utilized for the application of CHMs. Highlights To construct a nature identification model for analysis of the cold-hot-neutral nature of CHMs according to the compounds in CHMs.

Ethnopharmacological relevance : Traditional Chinese Medicine (TCM) has been widely used as an approach worldwide. Chinese Medicines (CMs) had been used to treat and prevent viral infection pneumonia diseases for thousands of years and had accumulated a large number of clinical experiences and effective prescriptions. Aim of the study : This research aimed to systematically excavate the classical prescriptions of Chinese Medicine (CM), which have been used to prevent and treat Pestilence (Wenbing, Wenyi, Shiyi or Yibing) for long history in China, to obtain the potential prescriptions and ingredients to alternatively treat COVID-19. Materials and methods We developed the screening system based on data mining, molecular docking and network pharmacology. Data mining and association network were used to mine the high-frequency herbs and formulas from ancient prescriptions. Virtual screening for the effective components of high frequency CMs and compatibility Chinese Medicine was explored by a molecular docking approach. Furthermore, network pharmacology method was used to preliminarily uncover the molecule mechanism. Results 574 prescriptions were obtained from 96,606 classical prescriptions with the key words to treat “Warm diseases (Wenbing)”, “Pestilence (Wenyi or Yibing)” or “Epidemic diseases (Shiyi)”. Meanwhile, 40 kinds of CMs, 36 CMs-pairs, 6 triple-CMs-groups existed with high frequency among the 574 prescriptions. Additionally, the key targets of SARS-COV-2, namely 3CL hydrolase (Mpro) and angiotensin-converting enzyme 2(ACE2), were used to dock the main ingredients from the 40 kinds by the LigandFitDock method. A total of 66 compounds components with higher frequency were docked with the COVID-19 targets, which were distributed in 26 kinds of CMs, among which Gancao (Glycyrrhizae Radix Et Rhizoma), HuangQin (Scutellariae Radix), Dahuang (Rhei Radix Et Rhizome) and Chaihu (Bupleuri Radix) contain more potential compounds. Network pharmacology results showed that Gancao (Glycyrrhizae Radix Et Rhizoma) and HuangQin (Scutellariae Radix) CMs-pairs could also interact with the targets involving in immune and inflammation diseases. Conclusions These results we obtained probably provided potential candidate CMs formulas or active ingredients to overcome COVID-19. Prospectively, animal experiment and rigorous clinic studies are needed to confirm the potential preventive and treat effect of these CMs and compounds., Graphical abstract Image 1

Ethnopharmacological relevance Danshen, the dried rhizome of Salvia miltiorrhiza Bge., is widely used to treat cardio-cerebrovascular diseases in China. However, its role in nourishing blood, which has been detailed in historical literature for thousands of years, is perpetually disputed in the academic field. Moreover, there is no systematic research on Danshen in treating anemia. This research aimed to investigate the effects and mechanisms of Danshen on anemia in a zebrafish model based on the results of a network pharmacology study. Materials and methods The network pharmacology study was based on the screening of chemical components and related targets from TCMSP and SwissADME database. The genes associated with anemia were obtained from DisgeNet database, and the genes with the intersection of Danshen target genes were screened out. The Cytoscape 3.7.2 software package was used to construct the “ingredient–target–pathway” network. The exploration of target interaction by String system and the enrichment analysis by Metascape system, was used to discover the possible anti-anemia action mechanism of Danshen. Then, a zebrafish anemia model was induced by vinorelbine followed by the administration of aqueous/ethanol extract of Danshen in contrast to SiWu Decoction (SWD), which is generally acknowledged as a positive drug for tonifying blood. Afterward, the red blood cell signal, cardiac output, and blood flow velocity were detected to evaluate their blood-enriching effects. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the mRNA levels of hematopoietic-related factors, which were predicted in network pharmacology. Results Compounds and target screening hinted that 115 chemical targets from Danshen were related to anemia, KEGG pathway enrichment results suggested that the mechanism of Danshen in treating anemia was significantly related to the Jak-STAT signaling pathway. Pharmacodynamic results showed that aqueous extract of Danshen (DSAE) and ethanol extract of Danshen (DSEE) markedly enhanced the number of red blood cells, cardiac output, and blood flow velocity. Compared with DSAE, DSEE exerted anti-anemia effects at a lower dose; however, along with higher toxicity. PCR data demonstrated that DSAE and DSEE treatment both upregulated the mRNA expression of erythroid hematopoiesis-related factors in the Epo-JAK-STAT signaling pathway, such as Gata-1, Epo, EpoR, Jak2, STAT3, and STAT5. In general, DSAE exhibited higher activation of this signaling than DSEE. Conclusions These results indicated that DSAE and DSEE both possess blood-enriching functions related with their ability to promote Jak-STAT signaling. DSAE exerted lower toxicity and attenuated anemia over a wider dose range than DSEE, which suggests that DSAE may be more suitable for the treatment for anemia. These results presented experimental evidence for the clinical use of Danshen as an intervention for anemia, especially in chemotherapy-induced anemia.

Background: G-protein-coupled bile acid receptor (TGR5), a membrane bile acid receptor, regulates macrophage reactivity, and attenuates inflammation in different disease models. However, the regulatory effects of TGR5 in ischemia/reperfusion (I/R)-induced kidney injury and inflammation have not yet been extensively studied. Therefore, we hypothesize that Farnesiferol B, a natural TGR5 agonist, could alleviate renal I/R injury by reducing inflammation and macrophage migration through activating TGR5. Methods: Mice were treated with Farnesiferol B before I/R or sham procedures. Renal function, pathological analysis, and inflammatory mediators were examined. In vitro, the regulatory effects of Farnesiferol B on the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-&kappa, B) pathway in macrophages were investigated. Results: After I/R, Farnesiferol B-treated mice displayed better renal function and less tubular damage. Farnesiferol B reduced renal oxidative stress and inflammation significantly. In vitro, Farnesiferol B treatment alleviated lipopolysaccharide (LPS)-induced macrophage migration and activation, as well as LPS-induced NF-&kappa, B activation through TGR5. Conclusions: Farnesiferol B could protect kidney function from I/R-induced damage by attenuating inflammation though activating TGR5 in macrophages. Farnesiferol B might be a potent TGR5 ligand for the treatment of I/R-induced renal inflammation.

A novel data-based machine learning algorithm for predicting amyloid aggregation rates is reported in this paper. Based on a highly nonlinear projection from 16 intrinsic features of a protein and 4 extrinsic features of the environment to the protein aggregation rate, a feedforward fully connected neural network (FCN) with one hidden layer is trained on a dataset composed of 21 different kinds of amyloid proteins and tested on 4 rest proteins. FCN shows a much better performance than traditional algorithms, such as multivariable linear regression and support vector regression, with an average accuracy higher than 90%. Furthermore, by the correlation analysis and the principal component analysis, seven key features, folding energy, HP patterns for helix, sheet and helices cross membrane, pH, ionic strength, and protein concentration, are shown to constitute a minimum feature set for characterizing the amyloid aggregation kinetics.

As a major component of cell membrane lipids, Arachidonic acid (AA), being a major component of the cell membrane lipid content, is mainly metabolized by three kinds of enzymes: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Based on these three metabolic pathways, AA could be converted into various metabolites that trigger different inflammatory responses. In the kidney, prostaglandins (PG), thromboxane (Tx), leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) are the major metabolites generated from AA. An increased level of prostaglandins (PGs), TxA2 and leukotriene B4 (LTB4) results in inflammatory damage to the kidney. Moreover, the LTB4-leukotriene B4 receptor 1 (BLT1) axis participates in the acute kidney injury via mediating the recruitment of renal neutrophils. In addition, AA can regulate renal ion transport through 19-hydroxystilbenetetraenoic acid (19-HETE) and 20-HETE, both of which are produced by cytochrome P450 monooxygenase. Epoxyeicosatrienoic acids (EETs) generated by the CYP450 enzyme also plays a paramount role in the kidney damage during the inflammation process. For example, 14 and 15-EET mitigated ischemia/reperfusion-caused renal tubular epithelial cell damage. Many drug candidates that target the AA metabolism pathways are being developed to treat kidney inflammation. These observations support an extraordinary interest in a wide range of studies on drug interventions aiming to control AA metabolism and kidney inflammation.

Obesity and hyperlipidemia are the most prevalent independent risk factors of chronic kidney disease (CKD), suggesting that lipid accumulation in the renal parenchyma is detrimental to renal function. Non-esterified fatty acids (also known as free fatty acids, FFA) are especially harmful to the kidneys. A concerted, increased FFA uptake due to high fat diets, overexpression of fatty acid uptake systems such as the CD36 scavenger receptor and the fatty acid transport proteins, and a reduced β-oxidation rate underlie the intracellular lipid accumulation in non-adipose tissues. FFAs in excess can damage podocytes, proximal tubular epithelial cells and the tubulointerstitial tissue through various mechanisms, in particular by boosting the production of reactive oxygen species (ROS) and lipid peroxidation, promoting mitochondrial damage and tissue inflammation, which result in glomerular and tubular lesions. Not all lipids are bad for the kidneys: polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to help lag the progression of chronic kidney disease (CKD). Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.

Traditional Chinese Marine Medicine (TCMM) represents one of the medicinal resources for research and development of novel anticancer drugs. In this study, to investigate the presence of anticancer activity (AA) displayed by cold or hot nature of TCMM, we analyzed the association relationship and the distribution regularity of TCMMs with different nature (613 TCMMs originated from 1,091 species of marine organisms) via association rules mining and phylogenetic tree analysis. The screened association rules were collected from three taxonomy groups: (1) Bacteria superkingdom, Phaeophyceae class, Fucales order, Sargassaceae family, andSargassumgenus; (2) Viridiplantae kingdom, Streptophyta phylum, Malpighiales class, and Rhizophoraceae family; (3) Holothuroidea class, Aspidochirotida order, andHolothuriagenus. Our analyses showed that TCMMs with closer taxonomic relationship were more likely to possess anticancer bioactivity. We found that the cluster pattern of marine organisms with reported AA tended to cluster with cold nature TCMMs. Moreover, TCMMs with salty-cold nature demonstrated properties for softening hard mass and removing stasis to treat cancers, and species within Metazoa or Viridiplantae kingdom of cold nature were more likely to contain AA properties. We propose that TCMMs from these marine groups may enable focused bioprospecting for discovery of novel anticancer drugs derived from marine bioresources.

To study the influence of Radix aconiti lateralis preparata and Rhizoma zingiberis, two species of Chinese medicinal herbs with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of their effects.Forty-eight specific pathogen free Wistar rats were randomly divided into a Radix aconiti lateralis preparata group, a Rhizoma zingiberis group, and a control group. They were intragastrically treated with concentrated decoction of Radix aconiti lateralis preparata, Rhizoma zingiberis and normal saline respectively for 20 days. Toe temperature (TT), energy intake (EI), digestible energy (DE), and metabolizable energy (ME) were measured. The content of adenosine triphosphate (ATP) and energy charge (EC) in hepatic tissue were measured with high performance liquid chromatography (HPLC). The activity of ATPase and succinate dehydrogenase (SDH) in the liver were detected with chemical colorimetry. The gene expression in the liver was detected with Illumina's rat Ref-12 gene array. The differential expression genes were selected, annotated and classified based on Gene Ontology (GO). Real-time quantitative reverse-transcriptase PCR (Q-RT-PCR) was used to test the accuracy of results.Compared with the control group, the TT on the 10(th) day after the beginning of administration and ATP in the Radix aconiti lateralis preparata and Rhizoma zingiberis groups increased significantly (P0.05). EI/body mass (BM), DE/BM, ME/BM, the hepatic EC and the activity of Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and SDH of liver increased significantly only in the Radix aconiti lateralis preparata group (P0.05). There were 592 differential expression genes in the Radix aconiti lateralis preparata group and 1 159 in the Rhizoma zingiberis group compared with the control group. Among the differential expression genes, genes related to metabolic processes were the most significant based on GO analysis. There were 337 strips of gene differential expression in common in both Radix aconiti lateralis preparata and Rhizoma zingiberis groups compared with the control group.Herbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.

Platycodi Radix is the root of Platycodon grandiflorum (Jacq.) A. DC and has been used as a traditional medicine in China. According to the theory of traditional Chinese medicine, Platycodi Radix (PR) possesses the character of lung meridian tropism (Guijing) and has selective effects on the lung and respiratory system. The aim of this study was to confirm the antioxidant effects of saponins from Platycodi Radix (PRS), with emphasis on its selective inhibition of lipid peroxidation in different tissues. The hydroxyl radical scavenging activity was determined by a H2O2/Fe2+ system; a modified thiobarbituric acid reactive species assay was used to measure the lipid peroxide in rats' tissues. These antioxidant activities were compared to ascorbic acid (Vc). The results showed that PRS had antioxidant activities in various antioxidant systems. And the inhibition capability of lipid peroxidation of PRS and Vc were excellent, but differed greatly in different tissues. These results suggested that PRS had antioxidant effects and selective inhibition of lipid peroxidation. It indicated that the mechanism of Platycodi Radix to treat some diseases might be related to its antioxidant activity, especially its tissue selective effects. However, further study is needed.

Author(s): Fechner, Uli; de Graaf, Chris; Torda, Andrew E; Gussregen, Stefan; Evers, Andreas; Matter, Hans; Hessler, Gerhard; Richmond, Nicola J; Schmidtke, Peter; Segler, Marwin HS; Waller, Mark P; Pleik, Stefanie; Shea, Joan-Emma; Levine, Zachary; Mullen, Ryan; van den Broek, Karina; Epple, Matthias; Kuhn, Hubert; Truszkowski, Andreas; Zielesny, Achim; Fraaije, Johannes Hans; Gracia, Ruben Serral; Kast, Stefan M; Bulusu, Krishna C; Bender, Andreas; Yosipof, Abraham; Nahum, Oren; Senderowitz, Hanoch; Krotzky, Timo; Schulz, Robert; Wolber, Gerhard; Bietz, Stefan; Rarey, Matthias; Zimmermann, Markus O; Lange, Andreas; Ruff, Manuel; Heidrich, Johannes; Onlia, Ionut; Exner, Thomas E; Boeckler, Frank M; Bermudez, Marcel; Firaha, Dzmitry S; Holloczki, Oldamur; Kirchner, Barbara; Tautermann, Christofer S; Volkamer, Andrea; Eid, Sameh; Turk, Samo; Rippmann, Friedrich; Fulle, Simone; Saleh, Noureldin; Saladino, Giorgio; Gervasio, Francesco L; Haensele, Elke; Banting, Lee; Whitley, David C; Oliveira Santos, Jana Sopkova-de; Bureau, Ronan; Clark, Timothy; Sandmann, Achim; Lanig, Harald; Kibies, Patrick; Heil, Jochen; Hoffgaard, Franziska; Frach, Roland; Engel, Julian; Smith, Steven; Basu, Debjit; Rauh, Daniel; Kohlbacher, Oliver; Boeckler, Frank M; Essex, Jonathan W; Bodnarchuk, Michael S; Ross, Gregory A; Finkelmann, Arndt R; Goller, Andreas H; Schneider, Gisbert; Husch, Tamara; Schutter, Christoph; Balducci, Andrea; Korth, Martin; Ntie-Kang, Fidele; Gunther, Stefan; Sippl, Wolfgang; Mbaze, Luc Meva'a

Chinese marine materia medica (CMMM) is a vital part of traditional Chinese medicine (TCM). Compared with terrestrial TCM, CMMM, derived from specific marine habitats, possesses peculiar chemical components with unique structures reflecting as potent pharmacological activities, distinct drug properties and functions. Nowadays, CMMM appears to be especially effective in treating such difficult diseases as cancers, diabetes, cardio-cerebrovascular diseases, immunodeficiency diseases and senile dementia, and therefore has become an important medicinal resource for the research and development of new drugs. In recent years, such development has attracted wide attention in the field of medicine. In this study, the CMMM resources in China were systematically investigated and evaluated. It was found that the historic experiences of Chinese people using CMMM have continuously accumulated over a period of more than 3600 years, and that the achievements of the research on modern CMMM are especially outstanding. By June 2015, 725 kinds of CMMMs from Chinese coastal sea areas have been identified and recorded, covering 1552 organisms and minerals. More than 3100 traditional prescriptions containing CMMMs have been imparted and inherited. However, the number of CMMMs is less than the 8188 terrestrial TCMs, from more than 12,100 medicinal terrestrial plants, animals and minerals. In the future, the research and development of CMMM should focus on the channel entries (TCM drug properties), compatibility, effective ingredients, acting mechanisms, drug metabolism and quality standard. This study reveals the high potential of CMMM development.

Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes fromin silicotarget prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, “the foundation of acquired constitution” that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications.

To explore appropriate methods for the research of the theory of Chinese medicine nature property and find the relationship between Nature-Family-Component of Chinese herbs.From perspective of systems biology, we used Associate Network to identify useful relationships among "Nature-Family-Component" of Herbs. In this work, Associate Network combines association rules mining method and network construction method to evaluate the complicate relationship among "Nature-Family-Component" of herbs screened.The results of association rules mining showed that the families had a close relationship with nature properties of herbs. For example, the families of Magnoliaceae, Araceae had a close relationship with hot nature with confidence of 100%, the families of Cucurbitaceae has a close relationship to cold nature with confidence of 90.91%. Moreover, the results of constructed Associate Network implied that herbs belonging to the same families generally had the same natures. In addition, some herbs belonging to different families may also have same natures when they contain the same main components.These results implied that the main components of herbs might affect their natures; the relationships between families and natures were based on the main compounds of herbs.