ABSTRACT
Bladder cancer is one of the most malignant tumors closely associated with macrophage immune dysfunction. The Chinese medicine polyporus has shown excellent efficacy in treating bladder cancer, with minimal side effects. However, its material basis and mechanism of action remain unclear. A new water-soluble polysaccharide (HPP) with strong immunomodulatory activity was isolated from the fungus Polyporus umbellatus (Pers.) Fries. HPP had an average molecular weight of 6.88 kDa and was composed mainly of an <-(1 â 4)-linked D-galactan backbone. The immunomodulatory activity of HPP was determined in vitro, and the results revealed that it could obviously increase the secretion of immune factors by IFN-γ-stimulated macrophages, including nitric oxide (NO), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), RANTES and interleukin-23 (IL-23), and the expression of the cell membrane molecule CD80. In addition, HPP was recognized by Toll-like receptor 2 (TLR2) and activated the signaling pathways of NF-κB and NLRP3 in a bladder cancer microenvironment model, indicating that HPP could enhance host immune system function. These findings demonstrated that HPP may be a potential immune modulator in the treatment of immunological diseases or bladder cancer therapy.
ABSTRACT
Bacillus CalmetteGuérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid IL2Rg/ (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b+ F4/80+ after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factorα, interleukin (IL)1ß, IL6, IL12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the prodifferential genes Spi1 protooncogene, early growth response protein 1, nuclear factor (NF)κB and protooncogene cFos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor.
Subject(s)
Adjuvants, Immunologic/therapeutic use , BCG Vaccine/therapeutic use , Macrophages/immunology , Urinary Bladder Neoplasms/therapy , Adjuvants, Immunologic/pharmacology , Animals , BCG Vaccine/immunology , Cell Line, Tumor , Cytokines/analysis , Cytokines/immunology , Disease Models, Animal , Gene Deletion , Humans , Immunotherapy , Interleukin Receptor Common gamma Subunit/genetics , Macrophage Activation , Male , Mice, Inbred NOD , Mice, SCID , Mycobacterium bovis/immunology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/immunologyABSTRACT
We developed a biodegradable photothermal therapeutic (PTT) agent, π-conjugated oligomer nanoparticles (F8-PEG NPs), for highly efficient cancer theranostics. By exploiting an oligomer with excellent near-infrared (NIR) absorption, the nanoparticles show a high photothermal conversion efficiency (PCE) up to 82%, surpassing those of reported inorganic and organic PTT agents. In addition, the oligomer nanoparticles show excellent photostability and good biodegradability. The F8-PEG NPs are also demonstrated to have excellent biosafety and PTT efficacy both in vitro and in vivo. This contribution not only proposes a promising oligomer-based PTT agent but also provides insight into developing highly efficient nanomaterials for cancer theranostics.
Subject(s)
Nanoparticles/chemistry , Neoplasms/therapy , Phototherapy , Theranostic Nanomedicine , A549 Cells , Animals , Cell Line, Tumor , Cell Survival/drug effects , HeLa Cells , Humans , Mice , Nanoparticles/metabolism , Neoplasms/pathologyABSTRACT
Advanced modified polyacrylonitrile (PAN) membrane with high adsorption property for heavy metal ions was designed and fabricated for the first time. The introduced diazoresin-ethylenediaminetetraacetic acid (DR-EDTA) layer could effectively absorb the metal ion, such as Cu2+, Pb2+, Hg2+ in the waste water. The effects of layers, metal ion concentration, pH, temperature and cycle time were investigated. The results showed that the adsorption isotherms for Cu2+ were well fitted by Langmuir model. The maximum adsorption capacity of the modified membrane for Cu2+ was approximately 47.6 mg/g. In addition, the prepared PAN-(DR-EDTA)3 membrane could be regenerated more than 720 h based on their adsorption/desorption cycles. The results demonstrated that the modified PAN membrane could be used as effective adsorbents for heavy metal removal from waste water.
ABSTRACT
Five previously undescribed terpenoids (cracrosons D-H), including three clerodane diterpenoids, together with 16 known diterpenoids were isolated from Croton crassifolius (Euphorbiaceae). Cracroson D features a previously undescribed carbon skeleton with an unprecedented cyclobutane ring. Their structures, including their absolute configurations, were elucidated using spectroscopic and single-crystal X-ray diffraction analyses along with CD calculations. A plausible biogenetic pathway for cracroson D is also proposed, which was supported by the experimental results. Additionally, all of the compounds were evaluated in vitro for cytotoxicity against T24 and A549 cells using the CCK-8 method.
Subject(s)
Croton/chemistry , Diterpenes/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cycloaddition Reaction , Diterpenes/chemical synthesis , Diterpenes/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Structure , Photochemical Processes , Structure-Activity RelationshipABSTRACT
Bladder cancer is one of the most malignant tumors closely associated with macrophages. Polyporus polysaccharide (PPS) has shown excellent efficacy in treating bladder cancer with minimal side effects. However, the molecular mechanisms underlying the effects of PPS in inhibiting bladder cancer remain unclear. In this study, we used macrophages cultured alone or with T24 human bladder cancer cell culture supernatant as study models. We found that PPS enhanced the activities of IFN-γ-stimulated RAW 264.7 macrophages, as shown by the release of inducible nitric oxide synthase (INOS), secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6, phagocytosis activity, as well as expression of M1 phenotype indicators, such as CD40, CD284 and CD86. PPS acted upstream in activation cascade of nuclear factor (NF)-κB signaling pathways by interfering with IκB phosphorylation. In addition, PPS regulated NF-κB (P65) signaling by interfering with Toll-like receptor (TLR)-4, INOS and cyclooxygenase (COX)-2. Our results indicate that PPS activates macrophages through TLR4/NF-κB signaling pathways.
Subject(s)
Antineoplastic Agents/pharmacology , Fungal Polysaccharides/pharmacology , Macrophage Activation/drug effects , Macrophages/drug effects , NF-kappa B/genetics , Polyporus/chemistry , Tumor Microenvironment/genetics , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Antineoplastic Agents/isolation & purification , Cell Line , Cell Line, Tumor , Culture Media, Conditioned/pharmacology , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fungal Polysaccharides/isolation & purification , Gene Expression Regulation , Humans , Interferon-gamma/pharmacology , Interleukin-6/genetics , Interleukin-6/metabolism , Macrophages/cytology , Macrophages/metabolism , Mice , Models, Biological , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Urinary Bladder/metabolism , Urinary Bladder/pathologyABSTRACT
Novel polysulfone membranes with bunch-like tertiary amine groups are synthesized with high ion selectivity and outstanding chemical stability for vanadium redox flow batteries (VRFBs). The bunch-like tertiary amine groups simultaneously act as an ionic conductor for proton hopping and vanadium ion transport obstacles. The performance of the membrane is tuned via controlling the grafting degree of the chloromethylated polysulfone. The results show that membranes show increasing proton over vanadium ion (σ/p) selectivity with increasing functional tertiary groups. VRFBs assembled with the prepared membranes demonstrate an impressive Coulombic efficiency of 98.9% and energy efficiency of 90.9% at a current density of 50 mA cm-2 . Furthermore, the prepared membrane reported in this work shows excellent stability in 1 m VO2+ solution at 35 °C over 240 h. Overall, the synthesized polymers provide a new insight into the design of high-performance membranes toward VRFB applications.
Subject(s)
Amines/chemistry , Electric Power Supplies , Membranes, Artificial , Polymers/chemistry , Protons , Sulfones/chemistry , Vanadium/chemistry , Amines/chemical synthesis , Electric Conductivity , Ions/chemistry , Models, Chemical , Molecular Structure , Oxidation-Reduction , Permeability , Proton Magnetic Resonance Spectroscopy , Spectroscopy, Fourier Transform Infrared , ThermogravimetryABSTRACT
Two new triterpenes and five new triterpene saponins, named ilexpusons A-G (1-7), as well as eight known compounds were isolated from Ilex pubescens. The structures of the new compounds were established by a combination of chemical and spectroscopic methods, including HRESIMS, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and NOESY. Additionally, the biological activity of compounds 1â-â15 against adenosine diphosphate-induced platelet aggregation in rabbit plasma was determined. Among the tested compounds, 1, 2, 5, 6, 8, 13, 14, and 15 exhibited significant inhibition of platelet aggregation in vitro.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Ilex/chemistry , Platelet Aggregation Inhibitors/isolation & purification , Platelet Aggregation/drug effects , Triterpenes/pharmacology , Animals , China , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Rabbits , Triterpenes/isolation & purificationABSTRACT
Four new triterpene saponins, rotundinosides A-D (1-4) and seven known triterpene saponins (5-11) were isolated from a methanol extract of the barks of Ilex rotunda Thunb. The new saponins were characterized as 3-O-ß-d-glucopyranosy1-(1â2)-ß-d-xylopyranosyl siaresinolic acid 28-O-ß-d-glucopyranoside (1), 3-O-[ß-d-glucopyranosy1-(1â2)-ß-d-xylopyranosyl]-3ß,19α-dihydroxyurs-12-en-28-oic-O-ß-d-glucopranosy1ester (2), 3-O-[α-l-rhamnopyranosyl-(1â2)-ß-d-glucopyranosy1-(1â2)-α-l-arabinopyranosyl]-3ß,19α-dihydroxyurs-12-en-28-oic-O-ß-d-glucopyranosy1 ester (3), and 3-O-α-l-rhamanopyranosyl-(1â2)-ß-d-glucopyranosy1-(1â2)-α-l-arabinopyranosyl ilexgenin B 28-O-ß-d-glucopyranosy1 ester (4), respectively. Their structures were established by extensive spectroscopic analysis, including HSQC, HMBC, (1)H-(1)H COSY, NOESY and acid hydrolysis, and also by the comparison of their spectroscopic data with those of related compounds. The known compounds 5-11 were all obtained from this species for the first time. The biological activity of compounds 1-11 against ADP induced platelet aggregation in rabbit plasma was determined. Among the tested compounds 1, 3, 5 and 10 exhibited strong inhibition of platelet aggregation in vitro, with IC50 values of 11.4±2.2, 10.4±1.3, 13.2±2.4, and 15.1±3.4µM, respectively.
Subject(s)
Blood Platelets/drug effects , Ilex/chemistry , Platelet Aggregation/drug effects , Saponins/chemistry , Triterpenes/chemistry , Animals , Molecular Structure , Plant Bark/chemistry , Rabbits , Saponins/isolation & purification , Triterpenes/isolation & purificationABSTRACT
OBJECTIVE: To establish a scientific method for identitication and evaluation of the Tibetan prescription Jia Ga Song Tang. METHODS: Volatile oil was extracted by water steam distillation and analyzed by GC-MS. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to the samples for chemical fingerprint pattern recognition research. RESULTS: 16 samples according to hierarchical cluster analysis (HCA) and principal component analysis (PCA) were divided into two classes, and results from two recognition analysis methods had good consistency. CONCLUSION: GC-MS-pattern recognition method was a kind of scientific, accurate and effective method for the quality evaluation of Jia Ga Song Tang.
Subject(s)
Drugs, Chinese Herbal/chemistry , Gas Chromatography-Mass Spectrometry , Oils, Volatile/chemistry , Quality Control , Cluster Analysis , Drugs, Chinese Herbal/standards , Oils, Volatile/standards , Principal Component Analysis , SteamABSTRACT
OBJECTIVE: To analyze the chemical components of volatile components from Jia Ga Song Tang. METHODS: The volatile oils were extracted by water steam distillation. The chemical components of essential oil were analyzed by GC-MS and quantitatively determined by a normalization method. RESULTS: 103 components were separated and 87 components were identified in the volatile oil of Zingiberis Rhizoma. 58 components were separated and 38 components were identified in the volatile oil of Myristicae Semen. 49 components were separated and 38 components were identified in the volatile oil of Amomi Rotundus Fructus. 89 components were separated and 63 components were identified in the volatile oil of Jia Ga Song Tang. CONCLUSION: Eucalyptol, ß-phellandrene and other terpenes were the main compounds in the volatile oil of Jia Ga Song Tang. Changes in the kinds and content of volatile components can provide evidences for scientific and rational compatibility for Jia Ga Song Tang.