ABSTRACT
The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the bloodâbrain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.
Subject(s)
Biomimetics , Blood-Brain Barrier , Silicon Dioxide , Animals , Silicon Dioxide/chemistry , Mice , Biomimetics/methods , Blood-Brain Barrier/metabolism , Manganese Compounds/chemistry , Biomimetic Materials/chemistry , Drug Delivery Systems/methods , Oxides/chemistry , Curcumin/therapeutic use , Curcumin/pharmacology , Disease Models, Animal , Neuroinflammatory Diseases , Inflammation , Macrophages , Brain/metabolism , Nanoparticles/chemistryABSTRACT
The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.
Subject(s)
Hydrogen Peroxide , Neoplasms , Female , Animals , Mice , Immunotherapy , Neoplasms/therapy , Antigen Presentation , Biological Transport , Tumor MicroenvironmentABSTRACT
OBJECTIVE: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically. METHODS: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology. RESULTS: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells. CONCLUSION: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.
Subject(s)
Drugs, Chinese Herbal , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Molecular Docking Simulation , Network Pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , ErbB ReceptorsABSTRACT
BACKGROUND: Quantitativereal-time reverse transcriptase polymerase chain reaction is the common method to quantify relative gene expression. Normalizating using reliable genes is critical in correctly interpreting expression data from qRT-PCR. Euscaphis konishii is a medicinal plant with a long history in China, which has various chemical compounds in fruit. However, there is no report describing the selection of reference genes in fruit development of Euscaphis konishii. METHODS: We selected eight candidate reference genes based on RNA-seq database analysis, and ranked expression stability using statistical algorithms GeNorm, NormFinder, BestKeeper and ReFinder. Finally, The nine genes related to the anthocyanin synthesis pathway of Euscaphis konishii were used to verify the suitability of reference gene. RESULTS: The results showed that the stability of EkUBC23, EkCYP38 and EkGAPDH2 was better, and the low expression reference genes (EkUBC23 and EkCYP38) were favourable for quantifying low expression target genes, while the high expression reference gene (EkGAPDH2) was beneficial for quantifying high expression genes. In this study, we present the suitable reference genes for fruit development of Euscaphis konishii based on transcriptome data, our study will contribute to further studies in molecular biology and gene function on Euscaphis konishii and other closely related species.
ABSTRACT
OBJECTIVE: This study aimed to investigate the effects of liraglutide on the body weight set point (BWSP) in diet-induced obese rats and to determine the relationship between BWSP and hypothalamic arcuate nucleus (ARC) microglial activation. METHODS: Diet-induced obesity (DIO) rats were divided into three groups: continuous high-fat diet (HFD) plus saline, HFD with liraglutide, and HFD with liraglutide pair feeding. Body weight, BWSP, inflammatory cytokines, suppressor of cytokine signaling 3, orexigenic/anorexigenic proteins, apoptosis, and microglia in the ARC were assessed. The effect of liraglutide on the Notch-1 signaling pathway and its relationships with nuclear factor-κB and p38 mitogen-activated protein kinase were also investigated in a lipopolysaccharide (LPS)-induced microglia activation model. RESULTS: Liraglutide reduced BWSP; reversed adverse changes in hypothalamic inflammation, suppressor of cytokine signaling 3, and apoptosis; and diminished microgliosis in DIO rats. The BWSP showed a linear correlation with ARC microglial density. Liraglutide inhibited LPS-induced M1 microglial polarization and promoted microglial polarization to the M2 phenotype, diminishing inflammatory cytokine expression. Liraglutide inhibited Notch-1 signaling pathway activation and decreased nuclear factor-κB and p38 mitogen-activated protein kinase pathway activation in LPS-stimulated microglia. CONCLUSIONS: Liraglutide can reduce BWSP in DIO rats. There is a linear correlation between hypothalamic microgliosis and BWSP. Liraglutide reduces excessive microglial activation and inflammation, which may contribute to BWSP reduction.
Subject(s)
Diet, High-Fat/adverse effects , Hypoglycemic Agents/therapeutic use , Hypothalamus/drug effects , Liraglutide/therapeutic use , Microglia/drug effects , Obesity/drug therapy , Animals , Humans , Hypoglycemic Agents/pharmacology , Hypothalamus/pathology , Liraglutide/pharmacology , Male , Rats , Rats, Sprague-DawleyABSTRACT
In this paper, we used tongue coating to obtain metabolites in patients with coronary heart disease (CHD) and chronic renal failure (CRF). The metabolites were analyzed to discover the substance that serves as the underlying basis of the damp phlegm pattern. This analysis is based on the Traditional Chinese Medicine (TCM) theory of "different diseases have the same pattern." The metabolic spectrum was obtained through the Gas Chromatography Mass Spectrometry coupling techniques and analyzed by searching the METLIN and HMDB databases. Some metabolites related to amino acids and glucose metabolism were identified in the tongue-coating samples from damp phlegm pattern patients by comparing them to nondamp phlegm pattern patients and healthy subjects. In addition, there were five common metabolites in the tongue-coating samples from CHD damp phlegm pattern patients compared to CRF damp phlegm pattern patients, which allowed us to understand the theory of "different diseases have the same pattern." In the future, the metabolites identified in this study may be used as noninvasive and convenient biomarkers to distinguish the damp phlegm pattern of CHD and CRF patients.
Subject(s)
Coronary Disease/diagnosis , Kidney Failure, Chronic/diagnosis , Metabolome , Tongue/chemistry , Adult , Aged , Aged, 80 and over , Amino Acids/metabolism , Biomarkers/metabolism , Case-Control Studies , Coronary Disease/metabolism , Discriminant Analysis , Female , Gas Chromatography-Mass Spectrometry , Glucose/metabolism , Humans , Kidney Failure, Chronic/metabolism , Male , Medicine, Chinese Traditional/methods , Middle Aged , WettabilityABSTRACT
Six new ellagitannins, brevipetins B-G (5 and 7-11), and a new phenolic glucoside, brevipetin A (4), along with six known compounds were isolated from the traditional Chinese medicinal plant Cleidion brevipetiolatum. Their structures and absolute configurations were determined by spectroscopic analyses, chemical methods, and TD-DFT-ECD calculations. Compounds 5-11 exhibited NO inhibitory effects with IC50 values of 1.9-8.2 µM, and 9 showed the most potent inhibitory effect (IC50: 1.9 µM). An in vivo anti-inflammatory assessment of 9 showed that it exerts therapeutic effects in both the carrageenan-induced rat paw edema and collagen-induced arthritis (CIA) models at 50 mg/kg oral administration. The enhanced protein and mRNA expression levels of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in LPS-stimulated RAW 264.7 cells were dose-dependently suppressed by 9. An anti-inflammatory mechanistic study revealed that 9 suppressed NF-κB activity by inhibiting IκBα phosphorylation and blocking translocation of p65 from the cytosol to the nucleus. Therefore, 9 might have the potential to be developed as a lead compound for relieving rheumatoid arthritis.
Subject(s)
Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Arthritis, Rheumatoid/drug therapy , Euphorbiaceae/chemistry , Hydrolyzable Tannins/isolation & purification , Hydrolyzable Tannins/therapeutic useABSTRACT
The combined technique of Liquid chromatography-mass spectrometry (LC/MS) is regarded as one of the most powerful analytical techniques for the analysis of traditional Chinese medicine (TCM) since it combines the high efficiency of LC separation with the confident structural identification of mass spectrometric detection.Studieson pharmacodynamic material basisof TCM are key to TCM modern research.This paper briefly reviewed its application in the study of chemical components,serum pharmacochemistry and metabonomics of TCM,as well as the study of the fingerprints of herbal drugs,cell membrane chromatography and affinity ultrafiltration mass pectrometry,which offered reference for further application of LC/MS in traditional Chinese medicine.
ABSTRACT
The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for as-cending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.
ABSTRACT
Liposomes have shown to be an excellent drug delivery system, but the short in vivo fate discourages their popularity. This work aimed to develop selenium-functionalized liposomes (SeLPs) for doxorubicin (Dox) delivery to prolong the systemic circulation of liposomes by in situ selenium coating and enhance the anticancer effect via the synergy between Dox and selenium. Dox-loaded SeLPs (Dox-SeLPs) were prepared by film hydration/active loading/in situ reduction technique and characterized by particle size, entrapment efficiency and morphology. The resulting Dox-SeLPs were 127â¯nm around in particle size (uncoated liposomes 107â¯nm) and were spherical in morphology. It was shown that Dox-SeLPs possessed a sustained release effect for Dox and could increase the cellular uptake of Dox compared with Dox-loaded liposomes (Dox-LPs). The accumulative Dox release from Dox-SeLPs was 46.5% and it was 64.9% for Dox-LPs within 84 h. Moreover, Dox-SeLPs exhibited slower drug release in the fetal bovine serum. Trafficking pathway study revealed that clathrin-mediated endocytosis and macropinocytosis were involved in the cellular uptake process of Dox-SeLPs. The in vitro cytotoxicity and apoptosis test indicated that Dox-SeLPs had higher cytotoxicity than that of free Dox and Dox-LPs. Dox-SeLPs showed a IC50 of 0.92⯱â¯0.16⯵g/mL on A549 cells, far lower than that of free Dox (4.40⯱â¯0.58⯵g/mL) and Dox-LPs (5.68⯱â¯0.73⯵g/mL). Dox-SeLPs significantly improved the pharmacokinetic property and enhanced the antitumor efficacy of Dox in tumor-bearing mice. In conclusion, SeLPs exhibit good sustained release for Dox and have synergic anticancer effect with Dox, which may be promising as drug delivery vehicle.
Subject(s)
Antineoplastic Agents/chemistry , Doxorubicin/analogs & derivatives , Doxorubicin/chemistry , Liposomes/chemistry , Selenium/chemistry , A549 Cells , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Apoptosis/drug effects , Cell Line, Tumor , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Drug Delivery Systems/methods , Endocytosis/drug effects , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Particle Size , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Rats , Rats, Sprague-DawleyABSTRACT
Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (d,l-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the systemic delivery of ABG.
Subject(s)
Antineoplastic Agents/administration & dosage , Bufanolides/administration & dosage , Bufanolides/pharmacokinetics , Drug Delivery Systems/methods , Nanostructures/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Drug Carriers/administration & dosage , Drug Liberation , Hep G2 Cells , Humans , Lactic Acid/administration & dosage , Lactic Acid/chemistry , Male , Micelles , Particle Size , Polyesters , Polyethylene Glycols , Polyglycolic Acid/administration & dosage , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats, Sprague-Dawley , Solubility , Tissue DistributionABSTRACT
AIM: To analyze the serum metabolites in patients with coronary heart disease (CHD) showing dampness syndrome and patients with chronic renal failure (CRF) showing dampness syndrome and to seek the substance that serves as the underlying basis of dampness syndrome in "same syndromes in different diseases." Methods. Metabolic spectrum by GC-MS was performed using serum samples from 29 patients with CHD showing dampness syndrome and 32 patients with CRF showing dampness syndrome. The principal component analysis and statistical analysis of partial least squares were performed to detect the metabolites with different levels of expression in patients with CHD and CRF. Furthermore, by comparing the VIP value and data mining in METLIN and HMDB, we identified the common metabolites in both patient groups. RESULTS: (1) Ten differential metabolites were found in patients with CHD showing dampness syndrome when compared to healthy subjects. Meanwhile, nine differential metabolites were found in patients with CRF showing dampness syndrome when compared to healthy subjects. (2) There were 9 differential metabolites identified when the serum metabolites of the CHD patients with dampness syndrome were compared to those of CRF patients with dampness syndrome. There were 4 common metabolites found in the serums of both patient groups.
Subject(s)
Coronary Disease/blood , Kidney Failure, Chronic/blood , Medicine, Chinese Traditional , Syndrome , Aged , China , Coronary Disease/complications , Coronary Disease/pathology , Female , Gas Chromatography-Mass Spectrometry , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/pathology , Least-Squares Analysis , Male , Middle Aged , Principal Component AnalysisABSTRACT
Psoriasis is a chronic and persistent inflammatory skin disease seriously affecting the quality of human life. In this study, we reported an ancient formula of Chinese folk medicine, the natural plant antimicrobial solution (PAMs) for its anti-inflammatory effects and proposed the primary mechanisms on inhibiting the inflammatory response in TNF-α/IFN-γ-induced HaCaT cells and imiquimod-induced psoriasis-like skin disease mouse model. Two main functional components of hydroxysafflor Yellow A and allantoin in PAMs were quantified by HPLC to be 94.2±2.2 and 262.9±12.5 µg/mL respectively. PAMs could significantly reduce the gene expression and inflammatory cytokines production of Macrophage-Derived Chemokine (MDC), IL-8 and IL-6 in TNF-α/IFN-γ-induced HaCaT cells. PAMs also significantly ameliorates the psoriatic-like symptoms in a mouse model with the evaluation scores for both the single (scales, thickness, erythema) and cumulative features were in the order of blank control < Dexamethasone < PAMs < 50% ethanol < model groups. The results were further confirmed by hematoxylin-eosin staining, RT-qPCR and immunohistochemistry. The down-regulated gene expression of IL-8, TNF-α, ICAM-1 and IL-23 in mouse tissues was consistent with the results from those of the HaCaT cells. The inhibition of psoriasis-like skin inflammation by PAMs was correlated with the inactivation of the translocation of P65 protein into cellular nucleus, indicating the inhibition of the inflammatory NF-κB signaling pathway. Taken together, these findings suggest that PAMs may be a promising drug candidate for the treatment of inflammatory skin disorders, such as psoriasis.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Drugs, Chinese Herbal/pharmacology , Phytotherapy , Psoriasis/drug therapy , Psoriasis/immunology , Active Transport, Cell Nucleus/drug effects , Aminoquinolines , Animals , Cell Line , Cell Survival/drug effects , Cytokines/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/chemistry , Female , Humans , Imiquimod , Interferon-gamma/metabolism , Mice, Inbred BALB C , NF-kappa B/metabolism , Psoriasis/pathology , Skin/drug effects , Skin/immunology , Skin/pathologyABSTRACT
Serum pharmacochemistry of traditional Chinese medicine(TCM) is an effective method to rapidly screen the effective substances and reveal the compatibility law of compound by identification and analysis of constituents migrating to blood after oral administration. In the last two decades, it has been universally accepted and widely applied in the field. With the cross-fusion with other disciplines, such as serum pharmacology, pharmacokinetics, metabolomics, network pharmacology and systems biology, serum pharmacochemistry shows comprehensive superiority in explaining drug changes in vivo and in vitro, interactions between drugs, interactions between drug and body, which coincides with the complexity of TCM compatibility, multi-components, multi-targets and multi-mechanisms. Based on the references related with the serum pharmacochemistry from CNKI scholar and Pubmed in 2013-2016, the research results of serum pharmacochemistry were statistically analyzed, and the key technical problems during the study of serum pharmacochemistry, for example, preparation of test sample, selection of experimental animal, determination of drug delivery scheme, method and time of the adoption blood, preparation and pretreatment of blood sample, as well as analysis of constituents migrating to blood, and the solving ways were empirically introduced. In addition, the development and comprehensive application of serum pharmacochemistry in TCM were summarized in this paper, hoping to lay a foundation for the further application of this method in TCM research.
ABSTRACT
Internal transcript spacer 2 (ITS2) is one of the broadly used standard core barcodes and also the only nuclear barcode in identification of Chinese traditional medicine. Although the DNA barcode method based on ITS2 is popular and has been used in Chinese Pharmacopoeia, its low discriminatory efficiency is still a problem to its extensive application. Therefore, further study is still necessary to explore its phylogenetic information for medicinal plants identification. In cells, ITS2 activity is based on its secondary structure. The secondary structures are particularly useful in phylogenetic analysis because they include information not found in the primary sequence. In this study ITS2 secondary structure of 40 samples from 26 species were predicted and used to explore their utility in addressing the identification problems of Chinese traditional medicine in Solanum. The secondary structures were predicted and aligned, and their consensus models were generated using the three different software of LocARNA, MASTR and PicXAA-R. RNAstat software was used to transform the secondary structures into 28 symbol code data for maximum parsimony (MP) analysis. The results showed that the phylogenetic information increased 88.57% after ITS2 secondary structure information has been added, and then the support values above 50%, 75% and 90% in the tree increased 19.05%, 66.67% and 66.67%, respectively, indicating that the identification of Solanum medical plants has been well resolved. Thus, our analysis suggests that ITS2 secondary structure information should be incorporated into the current DNA barcoding analysis as a beneficial supplement of phylogenetic information.
ABSTRACT
Osteoarthritis (OA) is a chronic disease and its etiology is complex. With increasing OA incidence, more and more people are facing heavy financial and social burdens from the disease. Genetics-related aspects of OA pathogenesis are not well understood. Recent reports have examined the molecular mechanisms and genes related to OA. It has been realized that genetic changes in articular cartilage and bone may contribute to OA's development. Osteoclasts, osteoblasts, osteocytes, and chondrocytes in joints must express appropriate genes to achieve tissue homeostasis, and errors in this can cause OA. MicroRNAs (miRNAs) are small noncoding RNAs that have been discovered to be overarching regulators of gene expression. Their ability to repress many target genes and their target-binding specificity indicate a complex network of interactions, which is still being defined. Many studies have focused on the role of miRNAs in bone and cartilage and have identified numbers of miRNAs that play important roles in regulating bone and cartilage homeostasis. Those miRNAs may also be involved in the pathology of OA, which is the focus of this review. Future studies on the role of miRNAs in OA will provide important clues leading to a better understanding of the mechanism(s) of OA and, more particularly, to the development of therapeutic targets for OA.
ABSTRACT
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and the interleukin-1 receptor (IL-1R). In the present study, the full-length cDNA of TRAF6 (Pt-TRAF6) was identified in a marine crab, Portunus trituberculatus. Pt-TRAF6 ORF is predicted to encode a 599-amino acid protein, including a RING type zinc finger, two TRAF-type zinc fingers, and a meprin and TRAF homology (MATH) domain. The overall amino acid sequence identity between Pt-TRAF6 and other TRAF6s ranged from 50.9 to 51.3% for shrimp and from 16.1 to 19.4% for insects. The Pt-TRAF6 gene contains six exons and five introns, which is different from the organization of the insect TRAF6 gene. Pt-TRAF6 transcripts were broadly expressed in all tissues tested, and their expression was higher in hemocytes, gills, the intestine, and heart than in muscle. Interestingly, the level of Pt-TRAF6 transcript differed between male and female crabs. After Vibrio alginolyticus or lipopolysaccharide (LPS) challenge, the Pt-TRAF6 transcript was down-regulated in hemocytes and up-regulated in gills. Moreover, Pt-TRAF6 expression was altered sooner in the LPS challenge group than in the V. alginolyticus challenge group. These results indicate that Pt-TRAF6 may respond to Gram-negative bacterial infections.
Subject(s)
Arthropod Proteins/genetics , Brachyura/genetics , Brachyura/immunology , TNF Receptor-Associated Factor 6/genetics , Animals , Arthropod Proteins/metabolism , Brachyura/metabolism , Brachyura/microbiology , DNA, Complementary/genetics , DNA, Complementary/metabolism , Female , Lipopolysaccharides/administration & dosage , Male , Molecular Sequence Data , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Sequence Analysis, Protein , Sex Characteristics , TNF Receptor-Associated Factor 6/metabolism , Vibrio alginolyticus/physiologyABSTRACT
The survey of traditional knowledge related to Chinese materia medica resources is the important component and one of the innovative aspects of the fourth national survey of the Chinese materia medica resources. China has rich traditional knowledge of traditional Chinese medicine (TCM) and the comprehensive investigation of TCM traditional knowledge aims to promote conservation and sustainable use of Chinese materia medica resources. Building upon the field work of pilot investigations, this paper introduces the essential procedures and key methods for conducting the survey of traditional knowledge related to Chinese materia medica resources. The essential procedures are as follows. First is the preparation phrase. It is important to review all relevant literature and provide training to the survey teams so that they have clear understanding of the concept of traditional knowledge and master key survey methods. Second is the field investigation phrase. When conducting field investigations, survey teams should identify the traditional knowledge holders by using the 'snowball method', record the traditional knowledge after obtaining prior informed concerned from the traditional knowledge holders. Researchers should fill out the survey forms provided by the Technical Specification of the Fourth National Survey of Chinese Materia Medica Resources. Researchers should pay particular attention to the scope of traditional knowledge and the method of inheriting the knowledge, which are the key information for traditional knowledge holders and potential users to reach mutual agreed terms to achieve benefit sharing. Third is the data compilation and analysis phrase. Researchers should try to compile and edit the TCM traditional knowledge in accordance with intellectual property rights requirements so that the information collected through the national survey can serve as the basic data for the TCM traditional knowledge database. The key methods of the survey include regional division of Chinese materia medica resources, interview of key information holders and standardization of information.' In particular, using "snowball method" can effectively identify traditional knowledge holder in the targeted regions and ensuring traditional knowledge holders receiving prior informed concerned before sharing the information with researcher to make sure the rights of traditional knowledge holders are protected. Employing right survey methods is not only the key to obtain traditional knowledge related to Chinese materia medica resources, but also the pathway to fulfill the objectives of access and benefit sharing stipulated in Convention on Biological Resources. It will promote the legal protection of TCM traditional knowledge and conservation of TCM intangible, cultural heritage.
Subject(s)
China , Data Collection , Databases, Pharmaceutical , Drugs, Chinese Herbal , Materia Medica , Medicine, Chinese TraditionalABSTRACT
A 2-year field experiment was conducted in 2011 and 2012 to investigate the effects of phosphorus (P) fertilization on the leaf area index (LAI), dry matter accumulation (DMA), and P use efficiency (PUE) of maize in wheat/maize/soybean intercropping system. Five P fertilization rates were installed, i.e., 0, 45, 90, 135, and 180 kg P2O5 x hm(-2) for wheat, marked as WP0, WP1, WP2, WP3, and WP4, respectively, and 0, 37.5, 75, 112.5, and 150 kg P2O5 x hm(-2) for maize, marked as MP0, MP1, MP2, MP3, and MP4, respectively. During the coexisted growth periods of wheat and maize, P fertilization increased the LAI, leaf area duration (LAD), and stem and leaf DMA of maize significantly. After the jointing stage of maize, the maize LAI, LAD, DMA, and crop growth rate (CGR) all decreased after an initial increase with the increasing P rate, with the maximum growth in treatment MP2 or MP3. During the reproductive stage of maize, the maize dry mass translocation from vegetative to reproductive organ increased with increasing P fertilization rate, and the grain yield of both maize and whole cropping system increased firstly and decreased then, with the maximum grain yield of maize and whole cropping system being 6588 and 11955 kg x hm(-2) in treatment P3, respectively. The P apparent recovery efficiency of maize was the highest (26.3%) in treatment MP2, being 82.6%, 38.4%, and 152.9% higher than that in MP1 (14.4%), MP3 (19.0%), and MP4 (10.4%), respectively. In sum, for the wheat/maize/soybean intercropping system, applying appropriate amount of P fertilizer could promote maize growth, alleviate the impact of wheat on maize, and consequently, increase the P apparent recovery efficiency of maize. In this study, the appropriate P fertilization rate was 75-112.5 kg P2O5 x hm(-2).
Subject(s)
Agriculture/methods , Biomass , Phosphorus/metabolism , Plant Leaves , Zea mays/growth & development , Fertilizers , Plant Leaves/anatomy & histology , Glycine max/growth & development , Triticum/growth & development , Zea mays/metabolismABSTRACT
Alpinetin, one of the main constituents of the seeds of Alpinia katsumadai Hayata, belonging to flavonoids, has been known to exhibit antibacterial, anti-inflammatory and other important therapeutic activities. The purpose of this study was to investigate the protection of alpinetin on inflammation in Lipopolysaccharide (LPS) stimulated Raw 264.7 cells and LPS induced vivo lung injury model. The effects of alpinetin on pro-inflammatory cytokines and signaling pathways were analyzed by enzyme-linked immunosorbent assay and Western blot. The results showed that alpinetin markedly inhibited the LPS- induced TNF-α, IL-6 and IL-1ß production both in vitro and vivo. Furthermore, alpinetin blocked the phosphorylation of IκBα protein, p65, p38 and extracellular signal-regulated kinase (ERK) in LPS stimulated RAW 264.7 cells. From in vivo study, it was also observed that alpinetin attenuated lung histopathologic changes in mouse models. These results suggest that alpinetin potentially decreases the inflammation in vitro and vivo, and might be a therapeutic agent against inflammatory diseases.