Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

Combination of omics, bioinformatics, molecular docking, and experimental validation to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen.

Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl4-induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)-extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH3, and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.

Enterotoxigenic Bacteroides fragilis (ETBF) Enhances Colorectal Cancer Cell Proliferation and Metastasis Through HDAC3/miR-139-3p Pathway.

Enterotoxigenic Bacteroides fragilis (ETBF) is believed to promote the malignant process of colorectal cancer (CRC), but the underlying molecular mechanism still needs to be revealed. CRC cells (SW480 and HCT-116) were treated with ETBF strain. Cell proliferation, invasion and, migration were evaluated by cell counting kit 8 assay, EdU assay, colony formation assay, transwell assay, and wound healing assay. Protein expression was analyzed by western blot. MicroRNA (miR)-139-3p and histone deacetylase 3 (HDAC3) expression levels in tissues and cells were determined by qRT-PCR. Xenograft tumor model was conducted to evaluate the effect of miR-139-3p on CRC tumor growth. ETBF treatment could promote CRC cell proliferation, invasion and migration. MiR-139-3p expression was decreased by ETBF, and its overexpression reversed the effect of ETBF on CRC cell progression. HDAC3 negatively regulated miR-139-3p expression, and its overexpression facilitated CRC cell behaviors via reducing miR-139-3p expression. Moreover, HDAC3 expression was increased by ETBF, and its knockdown also abolished ETBF-mediated CRC cell progression. Additionally, miR-139-3p overexpression could reduce CRC tumor growth in vivo. ETBF aggravated CRC proliferation and metastasis via the regulation of HDAC3/miR-139-3p axis. The discovery of ETBF/HDAC3/miR-139-3p axis may provide a new direction for CRC treatment.

Eucommiae Folium and Active Compounds Protect Against Mitochondrial Dysfunction-Calcium Overload in Epileptic Hippocampal Neurons Through the Hypertrophic Cardiomyopathy Pathway.

Epilepsy is a chronic brain disease and often occurs suddenly for no reason. Eucommiae folium (EF), an edible herb, can be used in the treatment of various kinds of brain diseases in clinic. From the perspective of safety and efficacy, EF is especially suitable for the treatment of chronic brain diseases. With the help of biolabels, this study was aimed to explore the value and feasibility of EF in the treatment of epilepsy. Proteomics and metabolomics were used to explore the biolabels of EF intervention in brain tissues. Bioinformatics was then applied to topologically analyze its neuroprotective effects and mechanisms and material basis based on biolabels, which were validated in an animal model. The biolabel-led research revealed that EF may exert the therapeutic potential to treat brain diseases through the interaction between multiple compounds and multiple targets, among which its therapeutic potential for epilepsy is particularly prominent. In the pentylenetetrazole-induction model, EF and four active compounds (oleamide, catechol, chlorogenic acid, and kaempferol) protected epileptic hippocampal neurons (Nissl and FJB staining) against mitochondrial dysfunction (MYH6, MYL3, and MYBPC3, etc.) and calcium overload (TNNI3, TNNC1, and TNNT2, etc.) through the hypertrophic cardiomyopathy pathway. This study provides new evidence and insights for the neuroprotective effects of EF, in which four active compounds may be potential drug candidates for the treatment of epilepsy.

Key genes and potential drugs in age-related hearing loss: transcriptome analysis of cochlear hair cells in old mice.

This study aimed to dig new molecular mechanisms and medications for age-related hearing loss (ARHL or presbycusis) by extracting common results of publicly available datasets. Based on five datasets (GSE153882, GSE121856, GSE98070, GSE45026, and GSE98071) in studies of cochlear hair cells, we explored the interrelationships among presbycusis-related genes, including gene interactions, enrichment analysis, miRNA-mRNA matching pairs, and potential new drugs. Together, there were 25 common increased mRNAs. A total of 183 drugs can simultaneously target 11 of these mRNAs. In the interaction network, hub genes included: Cbln1, Prl, Mpp6 and Gh. Meanwhile, there were 74 common decreased mRNAs. The hub genes include Cdkn1a, Egr1, and Ctgf. After de-duplication, the 25 common increased mRNAs had 946 matched miRNAs, with 34 decreased ones; and the 74 decreased mRNAs had 1164 matched miRNAs, with 26 increased ones. Between the inhibitors of increased mRNAs and enhancers of decreased mRNAs, there were 26 common drugs. Besides, we discovered six key genes that may play a crucial role in the onset of presbycusis. In conclusion, by jointly analyzing multiple datasets, we found 25 common increased mRNAs (e.g., Cbln1, Prl, Mpp6 and Gh) and 74 common decreased mRNAs (Cdkn1a, Egr1, and Ctgf), as well as 34 potential therapeutic miRNAs and 26 pathogenic miRNAs, and three candidate drugs (calcitriol, diclofenac, and diethylstilbestrol). They may provide new targets and strategies for mechanistic and therapeutic studies in ARHL.

Comprehensive Analysis of Alternative Polyadenylation Events Associated with the Tumor Immune Microenvironment in Colon Adenocarcinoma.

Objective: Colon adenocarcinoma (COAD) is one of the leading causes of cancer death worldwide. Alternative polyadenylation (APA) is relevant to the variability of the 3'-UTR of mRNA. However, the posttranscriptional dysregulation of APA in COAD is poorly understood. Methods: We collected APA data from The Cancer Genome Atlas (TCGA) COAD (n =7692). APA events were evaluated using PDUI values, and the prognostically significant APA events were screened by LASSO Cox regression to construct a prognostic model. Then, prognostic model functions and possible regulatory genes of characteristic APA events were analyzed. Finally, the immune regulatory network based on APA regulatory genes was analyzed and established. Results: A total of 95 APA events were found to influence the COAD outcomes. Among them, 39 genes were screened as characteristic prognostic APA events by LASSO Cox regression to construct a COAD prognostic signature. The analysis results suggested that a high signature score was associated with poor prognosis and was significantly correlated with a variety of immune cells, including NK and Th1, 2 and 17 cells. Further analysis showed that APA regulators mainly served roles in the prognosis of COAD. Based on the above results, we constructed an immunoregulatory network for APA regulatory genes-APA genes-immune cells. Conclusion: Our study revealed that APA events in COAD may regulate tumor progression by influencing immune cells, which provides a new direction for exploring the influencing mechanism of the tumor immune microenvironment and is expected to provide a potential new target for COAD immunotherapy.

Omics combined with network pharmacology reveal the neuroprotective mechanism of Sophora tonkinensis based on the biolabel research pattern: The treatment of Parkinson's disease against oxidative stress and neuroexcitatory toxicity.

Based on the biolabel research pattern, omics and network pharmacology were used for exploring the neuroprotection of Sophora tonkinensis (ST) in the treatment of brain diseases. Multi-omics were applied to investigate biolabels for ST intervention in brain tissue. Based on biolabels, the therapeutic potential, mechanism and material basis of ST for treating brain diseases were topologically analyzed by network pharmacology. A Parkinson's disease (PD) mouse model was used to validate biolabel analysis results. Four proteins and three metabolites were involved in two key pathways (alanine, aspartate and glutamate metabolism and arginine biosynthesis) and considered as biolabels. Network pharmacology showed that ST has the potential to treat some brain diseases, especially PD. Eight compounds (including caffeic acid, gallic acid and cinnamic acid) may serve as the material basis of ST treating brain diseases via the mediation of three biolabels. In the PD model, ST and its active compounds (caffeic acid and gallic acid) may protect dopaminergic neurons (maximum recovery rate for dopamine, 49.5%) from oxidative stress (E3 ubiquitin-protein ligase parkin, reactive oxygen species, nitric oxide, etc.) and neuroexcitatory toxicity (glutamate dehydrogenase, glutamine, glutamic acid, etc.). These findings indicated that omics and network pharmacology may contribute to the achievement of the objectives of this study based on the biolabel research pattern.

Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma.

Temozolomide (TMZ) resistance limits its use in glioblastoma (GBM). Exosomes can carry circular RNAs (circRNAs) to regulate chemoresistance. To date, the role of exosomal hsa_circ_0043949 (circ_0043949) in GBM resistance to TMZ is unclear. Relative expression of circ_0043949 in clinical samples, GBM cell lines, and exosomes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, invasion, and migration were analyzed via MTT, EdU, flow cytometry, transwell, and wound-healing assays. Relative protein levels were evaluated by western blotting. Target relationship was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays. Exosomes were isolated by ultracentrifugation and verified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The effect of exosomal circ_0043949 on TMZ resistance was validated by xenograft assay. Higher expression of circ_0043949 was gained in TMZ-resistant GBM samples and cells. Inhibition of circ_0043949 reduced TMZ resistance via decreasing IC50 of TMZ, repressing proliferation, invasion, migration, and inducing apoptosis in TMZ-resistant GBM cells. Circ_0043949 mediated integrinalpha1 (ITGA1) expression via function as a miR-876-3p sponge. Circ_0043949 was also upregulated in TMZ-resistant GBM cells-derived exosomes, and exosomal circ_0043949 increased the resistance of TMZ-resistant GBM cells to TMZ in xenograft models. TMZ-resistant GBM cells-derived exosomal circ_0043949 promoted TMZ resistance via upregulating ITGA1 expression via sequestering miR-876-3p, offering a potential target for the treatment of TMZ resistance in GBM.

Biolabel-led research pattern reveals serum profile in rats after treatment with Herba Lysimachiae: Combined analysis of metabonomics and proteomics.

In traditional Chinese medicine, Herba Lysimachiae (HL) is mainly used to treat rheumatic arthralgia. Current pharmacological studies also showed that HL has therapeutic potential for synovial diseases. HL is an oral drug, whose compounds need to enter the blood circulation before reaching the injured tissue, thus potentially causing activity or toxicity to the blood system. In this study, the biolabel-led research pattern was used to analyze the serum profile after HL intervention, based on which the safety and efficacy of HL were explored. Metabonomics and proteomics were combined to analyze the biolabels responsible for the interventions of HL in serum. Bioinformatics databases were used to screen for the material basis that may interfere with biolabels. Omics analysis showed that differentially expressed proteins (19) and metabolites (5) were identified and considered as the potential biolabels, which were involved in 8 biochemical processes (platelet activation and aggregation, blood glucose release, immune and inflammatory regulation, oxidative stress, endoplasmic reticulum stress, tumor progression, blood pressure regulation, and uric acid synthesis). Thirty-one compounds may be the material basis to interfere with 11 biolabels. The present research reveals that the potential activities and toxicities of HL can be explored based on the biolabel-led research pattern.

Nyap1 Regulates Multipolar-Bipolar Transition and Morphology of Migrating Neurons by Fyn Phosphorylation during Corticogenesis.

The coordination of cytoskeletal regulation is a prerequisite for proper neuronal migration during mammalian corticogenesis. Neuronal tyrosine-phosphorylated adaptor for the phosphoinositide 3-kinase 1 (Nyap1) is a member of the Nyap family of phosphoproteins, which has been studied in neuronal morphogenesis and is involved in remodeling of the actin cytoskeleton. However, the precise role of Nyap1 in neuronal migration remains unknown. Here, overexpression and knockdown of Nyap1 in the embryonic neocortex of mouse by in utero electroporation-induced abnormal morphologies and multipolar-bipolar transitions of migrating neurons. The level of phosphorylated Nyap1 was crucial for neuronal migration and morphogenesis in neurons. Furthermore, Nyap1 regulated neuronal migration as a downstream target of Fyn, a nonreceptor protein-tyrosine kinase that is a member of the Src family of kinases. Importantly, Nyap1 mediated the role of Fyn in the multipolar-bipolar transition of migrating neurons. Taken together, these results suggest that cortical radial migration is regulated by a molecular hierarchy of Fyn via Nyap1.

The active ingredients analysis of Herba Lysimachiae treating osteoarthritis based on the LC-MS/MS technology and public bioinformatics platforms.

Herba Lysimachiae inhibits synovial damage in osteoarthritis via regulating two bio labels (integrin alpha 2b/beta 3). However, the relevant active ingredients are still unknown. Here, the active ingredients of herbal medicines were analyzed based on the liquid chromatography-tandem mass spectrometry technology and public bioinformatics platforms. The liquid chromatography-tandem mass spectrometry technology was used for compound analysis, and public databases (PubChem BioAssay and STRING) were applied to establish the links between herbal compounds and both bio labels, and identify which herbal compounds may regulate these bio labels. Subsequently, the osteoarthritis model was used to confirm the results. Totally, ninety compounds in Herba Lysimachiae were identified based on the liquid chromatography-tandem mass spectrometry technology. Bioinformatics analysis showed that five compounds (myricetin, fisetin, esculetin, 7-hydroxycoumarin-4-acetic acid, and caffeic acid) may synergistically regulate bio labels through 11 targets, which may be the active ingredients of Herba Lysimachiae for osteoarthritis treatment. In the verification experiments, five compounds markedly suppressed the overexpression of bio labels in the synovium of the osteoarthritis model. In conclusion, the present study effectively and rapidly analyzed the active ingredients of Herba Lysimachiae for osteoarthritis treatment.

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction.

Rheumatoid arthritis (RA) is a systemic disease characterized by autoimmunity, joint inflammation, and cartilage destruction, which affects 0.5-1% of the population. Many compounds from herbal medicines show the potentials to treat RA. On this basis, the compounds with good pharmacokinetic behaviors and drug-likeness properties will be further studied and developed. Therefore, the herbal compounds with anti-RA activities were reviewed in this paper, and the cheminformatics tools were used to predict their drug-likeness properties and pharmacokinetic parameters. A total of 90 herbal compounds were analyzed, which were reported to be effective on RA models through anti-inflammation, chondroprotection, immunoregulation, antiangiogenesis, and antioxidation. Most of the herbal compounds have good drug-likeness properties. Most of the compounds can be an alternative and valuable source for anti-RA drug discovery.

Postoperative complications and prognosis after radical gastrectomy for gastric cancer: a systematic review and meta-analysis of observational studies.

BACKGROUND: Many observational studies have reported correlations between postoperative complications and prognosis after radical gastrectomy but the results are controversial. This meta-analysis was performed to investigate whether there is a correlation between postoperative complications and prognosis after radical gastrectomy. METHODS: Literature searches were performed in PubMed, EMBASE, and the Cochrane Library. Studies that investigated the correlations between any postoperative complications and prognosis after radical gastrectomy were included. The pooled hazard ratio (HR) with 95% confidence interval (CI) for postoperative complications regarding overall survival (OS) or recurrence-free survival (RFS) was calculated by using RevMan 5.3.5. Subgroup analyses were performed within pathological stages I, II, and III. RESULTS: Sixteen retrospective studies comprising 12,065 patients were included. The pooled HR (95% CI) for complications regarding OS was 1.79 (1.39, 2.30) and was 1.40 (1.06, 1.84) after excluding in-hospital mortality; the pooled HR (95% CI) for complications regarding RFS was 1.28 (1.10, 1.49). The pooled HR (95% CI) for infectious complications and leakage regarding OS was 1.86 (1.22, 2.83) and 2.02 (1.02, 4.00), respectively. The pooled HR (95% CI) for any reported postoperative complications regarding OS for stage I, II, and III diseases was 2.39 (0.77, 7.46), 4.35 (2.58, 7.35), and 2.84 (1.77, 4.56), respectively. CONCLUSIONS: Postoperative complications correlate with poor prognosis after radical gastrectomy. Such correlations are found in stage II and III gastric cancer patients but remain to be determined in stage I gastric cancer patients.

High level of CTP synthase induces formation of cytoophidia in cortical neurons and impairs corticogenesis.

De novo synthesis of the nucleotide CTP is catalyzed by the essential pyrimidine biosynthesis enzyme CTP synthase (CTPs), which forms large-scale filamentous structures consisting of CTPs termed cytoophidia in prokaryotes and in eukaryotes. Recent studies have shown that cytoophidia are abundant in neuroepithelial stem cells in Drosophila optic lobes and that overexpression of CTPs impairs optic lobe development. Whether CTPs and cytoophidia also play a role in the development of the mammalian cortex remains elusive. Here, we show that overexpression of CTPs by in utero electroporation in the embryonic mouse brain induces formation of cytoophidia in developing cortical neurons and impairs neuronal migration. In addition, the increase of cytoophidia accelerates neuronal differentiation and inhibits neural progenitor cell proliferation by reducing their mitotic activity. Furthermore, we discovered that the cytoophidia diffused during the early G1-phase of the cell cycle. Together, our findings show, for the first time, that CTPs play a significant role in the development of the mammalian cortex.

Aberrant expression of LIMK1 impairs neuronal migration during neocortex development.

Neuronal migration is essential for the formation of cortical layers, and proper neuronal migration requires the coordination of cytoskeletal regulation. LIMK1 is a serine/threonine protein kinase that mediates actin dynamics by regulating actin depolymerization factor/cofilin. However, the role of LIMK1 in neuronal migration and its potential mechanism remains elusive. Here, we found that using the in utero electroporation to overexpress LIMK1 and its mutants, constitutively active LIMK1 (LIMK1-CA) and dominant-negative LIMK1 (LIMK1-DN), impaired neuronal migration in the embryonic mouse brain. In addition, the aberrant expression of LIMK1-WT and LIMK1-CA induced abnormal branching and increased the length of the leading process, while LIMK1-DN-transfected neurons gave rise to two leading processes. Furthermore, the co-transfection of LIMK1-CA and cofilin-S3A partially rescued the migration deficiency and fully rescued the morphological changes in migrating neurons induced by LIMK1-CA. Our results indicated that LIMK1 negatively regulated neuronal migration by affecting the neuronal cytoskeleton and that its effects were partly mediated by cofilin phosphorylation.

Microarray Expression Analysis for the Paradoxical Roles of Acanthopanax senticosus Harms in Treating α-Synucleinopathies.

α-Synuclein is a key player in the pathogenesis of neurodegenerative disorders with Lewy bodies. Our previous studies have also showed that Acanthopanax senticosus harms (AS) could significantly suppress α-synuclein overexpression and toxicity. Identifying the RNAs related to α-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. Microarray expression profiling of long non-coding RNAs (lncRNAs) and mRNAs was undertaken in control non-transgenic and human α-synuclein transgenic mice. The effects of AS on central nervous system (CNS) in pathology and physiology were investigated based on the lncRNA/mRNA targets analysis. In total, 341 lncRNAs and 279 mRNAs were differentially expressed by α-synuclein stimulus, among which 29 lncRNAs and 25 mRNAs were involved in the anti-α-synucleinopathies mechanism of AS. However, the levels of 19/29 lncRNAs and 12/25 mRNAs in AS group were similar to those in α-synuclein group, which may cause potential neurotoxicity analogous to α-synuclein. This study demonstrated that some of lncRNAs/mRNAs were involved in α-synuclein related pathophysiology, and AS produced the bidirectional effects on CNS under pathological and physiological conditions.

Metabonomic Study of the Effects of Acanthopanax senticosus on Peripheral System of Rats.

Acanthopanax senticosus is extensively used to treat various nervous and cerebrovascular diseases in traditional medicinal systems in China and Russia. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry coupled with pattern recognition methods was used to investigate the effects of A. senticosus on the peripheral system in rats. The analysis of possible pathways influenced by A. senticosus was performed with MetaboAnalyst and Cytoscape software. After treatment with A. senticosus, 21 modulated metabolites in heart tissue, 20 in liver tissue, 14 in spleen tissue, 17 in lung tissue, 16 in kidney tissue, and 12 in a serum sample were identified and considered potential biomarkers of A. senticosus treatments. The regulation of some endogenous metabolites by A. senticosus could be beneficial for the treatment of several peripheral system diseases, such as hypertension, cancer, and oxidative stress, etc. However, there were also some upregulated endogenous metabolites producing potential toxicity to the peripheral system. A metabonomic analysis revealed that protection and toxicity coexisted in the effects of A. senticosus on the peripheral system, which may be a practical guide for its safe use and beneficial to the expansion of its application.

[Study on potential effect of Dioscorea nipponica in intervening peripheral system of rats based on metabonomic analysis].

To study the potential effect of Dioscorea nipponica(DN) in intervening peripheral system of rats based on metabolomic analysis. The identification of the potential intervention targets of DN in peripheral system may facilitate its safe application and therapeutic potential exploitation. Totally 20 male SD rats were randomly divided into the blank group and the DN-treated groups, with 10 rates in each group. The DN-treated group was orally administrated with DN extracts once a day for 5 days, with the dose of 80 mg x kg(-1) (equivalent to 15 g crude drug in human), and the blank group was given equal volume of saline once a day for 5 days. Heart, liver, spleen, lung, and kidney tissues and serum samples were collected from each rat 24 h later after the last administration. The ultra-performance liquid chromatography/quadrupole time-of-flight-mass spectrometry based metabolomics was used to investigate the effect of DN in intervening peripheral system of rats. After the treatment with DN, 5 modulated metabolites in heart tissue, 6 in liver tissue, 5 in spleen tissue, 3 in lung tissue, 5 in kidney tissue and 6 in serum sample were identified and considered as the potential intervention targets of DN. Effect of DN in regulating some endogenous metabolites was beneficial for protecting peripheral system, while that in other endogenous metabolites produced potential toxicity to peripheral system. The metabolomic analysis revealed the coexistence of protective and toxic effects of DN on peripheral system, which may be a practical guidance for its safe application and beneficial to the expansion of its application scope.

Therapeutic effect of Rhizoma Dioscoreae Nipponicae on gouty arthritis based on the SDF-1/CXCR 4 and p38 MAPK pathway: an in vivo and in vitro study.

Rhizoma Dioscoreae Nipponicae (RDN) is a widely used traditional Chinese herb, which is used to treat arthroncus, arthrodynia and arthritis. As is known to us, inflammatory mechanisms have played an important role in the occurrence, course and prognosis of gouty arthritis (GA). The aim of this study was to determine the characteristic expressed proteins of synovium in GA rat and synovial cell. The rat model of GA was induced by monosodium urate (MSU) crystal. Tissue samples were assayed by immunohistochemical method. The effects of RDN on Stromal cell-derived factor 1 (SDF-1), CXCR 4 and p38 mitogen-activated protein kinase (MAPK) were investigated in MSU crystal-induced rat. The levels of SDF-1 and mitogen-activated kinase kinase (MKK) 3/6 were measured by Western Blot in interleukin-1ß (IL-1ß) incubated fibroblast-like synoviocytes (FLS). A significant increase in the levels of SDF-1, CXCR 4 and p38 MAPK were observed in MSU crystal-induced rat. The increased SDF-1 and MKK 3/6 levels were observed in IL-1ß incubated FLS. With the treatment of RDN, the above changes were reverted back to near normal levels. RDN might have some therapeutic effects on GA through SDF-1/CXCR 4 and p38 MAPK pathway, and dioscin may be the active compound in RDN to exert therapeutic effect on GA.

Antifouling potential of the marine microalga Dunaliella salina.

Marine organisms have usually been viewed as sources of environmentally friendly compounds with antifouling activity. We performed a series of operations to investigate the antifouling potential of the marine microalga Dunaliella salina. For the ethyl acetate crude extract, the antialgal activity was significant, and the EC50 value against Skeletonema costatum was 58.9 µg ml(-1). The isolated purified extract was tested for antifouling activity, the EC 50 value against S. costatum was 21.2 µg ml(-1), and the LC50 against Balanus amphitrite larvae was 18.8 µg ml(-1). Subsequently, both UHR-TOF-MS and GC-MS were used for the structural elucidation of the compounds, and a series of unsaturated and saturated 16- and 18-carbon fatty acids were detected. The data suggested that the fatty acid extracts from D. salina possess high antifouling activity, and could be used as substitutes for potent, toxic antifouling compounds.