RÉSUMÉ
As an emerging tumor therapy, ideal oncolytic viruses preferentially replicate in malignant cells, reverse the immunosuppressive tumor microenvironment, and eventually can be eliminated by the patient. It is of great significance for cancer treatment to discover new excellent oncolytic viruses. Here, we found that WNV live attenuated vaccine WNV-poly(A) could be developed as a novel ideal oncolytic agent against several types of cancers. Mechanistically, due to its high sensitivity to type Ι interferon (IFN-Ι), WNV-poly(A) could specifically kill tumor cells rather than normal cells. At the same time, WNV-poly(A) could activate Dendritic cells (DCs) and trigger tumor antigen specific response mediated by CD8 + T cell, which contributed to inhibit the propagation of original and distal tumor cells. Like intratumoral injection, intravenous injection with WNV-poly(A) also markedly delays Huh7 hepatic carcinoma (HCC) transplanted tumor progression. Most importantly, in addition to an array of mouse xenograft tumor models, WNV-poly(A) also has a significant inhibitory effect on many different types of patient-derived tumor tissues and HCC patient-derived xenograft (PDX) tumor models. Our studies reveal that WNV-poly(A) is a potent and excellent oncolytic agent against many types of tumors and may have a role in metastatic and recurrent tumors.
Sujet(s)
Carcinome hépatocellulaire , Tumeurs du foie , Virus oncolytiques , Animaux , Souris , Lymphocytes T CD8+ , Lignée cellulaire tumorale , Immunité , Tumeurs du foie/thérapie , Récidive tumorale locale , Virus oncolytiques/métabolisme , Microenvironnement tumoral , Réplication viraleRÉSUMÉ
The genus Flavivirus comprises numerous emerging and re-emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live-attenuated vaccine (LAV), WNV-poly(A), by replacing 5' portion (corresponding to SL and DB domains in WNV) of 3'-UTR with internal poly(A) tract. WNV-poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single-dose vaccination elicited robust and long-lasting immune responses, conferring full protection against WNV challenge. Such "poly(A)" vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses.
Sujet(s)
Fièvre à virus West Nile , Vaccins contre le virus du Nil occidental , Régions 3' non traduites , Animaux , Anticorps antiviraux , Chlorocebus aethiops , Souris , Poly A , Cellules Vero , Fièvre à virus West Nile/prévention et contrôleRÉSUMÉ
Three new 3-hydroxy-3-methylglutaryl (HMG) flavone 7-O-diglycosides, argutosides A-C (1-3); two new flavone 7-O-triglycosides, argutosides D-E (4-5); and one known apigenin 7-O-triglycoside (6), were isolated from the leaves of Turpinia arguta. The structures of these compounds were elucidated by spectroscopic and chemical techniques. The NO inhibitory activities of compounds 1-6 were evaluated using lipopolysaccharide-induced RAW264.7 cells. Only compound 2 showed a moderate inhibitory effect on NO production with an IC50 value of 25.74µM. Compounds 1-6 were not cytotoxic to RAW264.7 cells at 10µM.
Sujet(s)
Flavones/composition chimique , Hétérosides/composition chimique , Magnoliopsida/composition chimique , Feuilles de plante/composition chimique , Animaux , Anti-inflammatoires/composition chimique , Souris , Structure moléculaire , Monoxyde d'azote/métabolisme , Cellules RAW 264.7RÉSUMÉ
Nine 14,15-secopregnane-type C21-steriosides, stauntosides U, V, V1-V3, W and C1-C3, as well as two known C21-steriosides, were isolated from the roots of Cynanchum stauntonii. Stauntosides U, V and V1-V3 share the same basic structural features of 8α:14α,14:16,15:20,18:20-tetraepoxy-14,15-secopregn-6-ene-3ß,5α,9α-triol, with the numbering system following that of C21-pregnanes. The aglycones of stauntosides U, V and V1-V3 are classified into two subcategories, the 5,9-dihydroxy groups and 5α:9α-peroxy bridge, according to the oxidative states of the two hydroxy groups at the C-5 and C-9 positions. The anti-inflammatory activity of the major compounds was assessed in an in vitro inflammatory model of mouse peritoneal macrophages using IC50 values of the inhibition of nitric oxide (NO) production as an indicator. Stauntosides V1 and V3 exhibited target activity with IC50 values of 9.3 µM and 12.4 µM, respectively, compared with dexamethasone, which was used as a positive control.
Sujet(s)
Cynanchum/composition chimique , Racines de plante/composition chimique , Prégnanes/composition chimique , Animaux , Anti-inflammatoires/composition chimique , Anti-inflammatoires/isolement et purification , Macrophages péritonéaux/effets des médicaments et des substances chimiques , Souris , Souris de lignée C57BL , Structure moléculaire , Monoxyde d'azote/métabolisme , Prégnanes/isolement et purificationRÉSUMÉ
Seven new sesquiterpenes (1, 3-8), a new sesquiterpene natural product (2), and two new lignans (9 and 10), together with 15 known compounds, were isolated from the fruits of Xanthium sibiricum. The structures of the new compounds were established by NMR spectroscopic analysis, ECD calculations, and Mo2(OAc)4-induced circular dichroism, with the structures of 1 and 4 confirmed by single-crystal X-ray diffraction. Compound 1 is the first example of a 3/5/6/5 tetracyclic eudesmane sesquiterpene lactone formed at C-6 and C-7. In turn, compound 4 is the first example of a natural xanthane tetranorsesquiterpene, while compounds 5-8 are the first xanthane trinorsesquiterpenes found to date. Compounds 8, 11-15, 17, and 24 exhibited indirect anti-inflammatory activity by suppressing the lipopolysaccharide-induced proinflammatory factors in BV2 microglial cells, with IC50 values between 1.6 and 8.5 µM. Furthermore, compounds 13 and 17 exhibited anti-inflammatory activity against ear edema in mice produced by croton oil, with inhibition rates of 46.9% and 37.7%, respectively. Compounds 8, 11, 12, 23, and 24 exhibited potent activity against influenza A virus (A/FM/1/47, H1N1) with IC50 values between 3.7 and 8.4 µM.
Sujet(s)
Anti-inflammatoires/isolement et purification , Anti-inflammatoires/pharmacologie , Médicaments issus de plantes chinoises/isolement et purification , Médicaments issus de plantes chinoises/pharmacologie , Lignanes/isolement et purification , Lignanes/pharmacologie , Sesquiterpènes/isolement et purification , Sesquiterpènes/pharmacologie , Xanthium/composition chimique , Animaux , Anti-inflammatoires/composition chimique , Cristallographie aux rayons X , Chiens , Médicaments issus de plantes chinoises/composition chimique , Fruit/composition chimique , Sous-type H1N1 du virus de la grippe A/effets des médicaments et des substances chimiques , Concentration inhibitrice 50 , Lignanes/composition chimique , Macrophages/effets des médicaments et des substances chimiques , Cellules rénales canines Madin-Darby/effets des médicaments et des substances chimiques , Souris , Conformation moléculaire , Structure moléculaire , Résonance magnétique nucléaire biomoléculaire , Sesquiterpènes/composition chimique , Cellules Vero/effets des médicaments et des substances chimiquesRÉSUMÉ
Three new saikosaponin analogs, comastomasaponins I-K (1-3), were isolated from the aerial portions of Comastomapedunculatum. The structures of these compounds were elucidated on the basis of spectroscopic data analysis, and their nitric oxide production inhibitory activity was evaluated invitro.
Sujet(s)
Araliaceae/composition chimique , Médicaments issus de plantes chinoises/isolement et purification , Acide oléanolique/analogues et dérivés , Saponines/isolement et purification , Médicaments issus de plantes chinoises/composition chimique , Médicaments issus de plantes chinoises/pharmacologie , Structure moléculaire , Monoxyde d'azote/biosynthèse , Résonance magnétique nucléaire biomoléculaire , Acide oléanolique/composition chimique , Acide oléanolique/isolement et purification , Parties aériennes de plante/composition chimique , Saponines/composition chimiqueRÉSUMÉ
P2X7 is the most important subtype of the ATP receptors known so far. Recent investigations showed that the downstream signaling pathway of P2X7 is coupled with several key inflammatory molecules including IL-1beta and IL-18, this suggests P2X7 might have roles in the inflammatory diseases. Moreover, attenuation of P2X7 by selective antagonists in vitro and knockout mice in vivo reducing the inflammatory response indicated that P2X7 is a potential therapeutic target for inflammatory diseases. However, most previous studies on P2X7 were focused on nerve system diseases most, while its effects in inflammatory respiratory diseases, especially in asthma, chronic obstructive pulmonary disease (COPD) and lung cancer have been poorly investigated. In this paper, we reviewed the research progress on the structure, distribution, biological activities of P2X7 and its relationship with inflammatory respiratory diseases including asthma, COPD and lung cancer, along with the development of P2X7 antagonist as therapeutics.
Sujet(s)
Inflammation/métabolisme , Antagonistes des récepteurs purinergiques P2X/usage thérapeutique , Récepteurs purinergiques P2X7/métabolisme , Maladies de l'appareil respiratoire/métabolisme , Animaux , Asthme/traitement médicamenteux , Asthme/métabolisme , Humains , Inflammation/traitement médicamenteux , Interleukine-18/métabolisme , Interleukine-1 bêta/métabolisme , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/métabolisme , Souris , Polymorphisme de nucléotide simple , Broncho-pneumopathie chronique obstructive/traitement médicamenteux , Broncho-pneumopathie chronique obstructive/métabolisme , Récepteurs purinergiques P2X7/composition chimique , Récepteurs purinergiques P2X7/génétique , Maladies de l'appareil respiratoire/traitement médicamenteuxRÉSUMÉ
Eight compounds were isolated from the leaves of Turpinia arguta by various chromatograhic techniques such as D101 macroporous resin, polyamide, Sephadex LH-20,and HPLC chromatography, and their structures were elucidated as rhoifolin (1), apigenin-7-O- [2"-O-alpha-L-rhamnopyranosyl-6"-O-alpha-L-rhamnopyranosyl] -beta-D-glucopyranoside (2), acacetin-7-O- [2"-O-alpha-L-rhamnopyranosyl-6"-O-beta-D-glucopyranosyl] -beta-D-glucopyranoside (3), acacetin-7-O- [2"-O-alpha-L-rhamnopyranosyl-6"-O-alpha-L-rhamnopyranosyl] -beta-D-glucopyranoside(neobudofficide, 4), luteolin-7-O-[2"-O-beta-D-glucopyranosyl] -beta-D-glucopyranoside (5), chrysoeiml-7-O-[2"-O-beta-D-glucopyranosyl] -beta-D-glucopyranoside (6), acacetin-7-O-alpha-L-rhamnopyranosyl-(1 --> 6) -O-beta-D-glucopyranoside (buddleoside, linarin, 7), and apigenin 6, 8-di-C-beta-D-glucopyranoside (8) on the basis of spectral data analysis. Compounds 3-8 were isolated from T. arguta for the first time. Compounds 2, 3 showed weak anti-inflammatory effect on LPS-stimulated RAW264.7 cell.
Sujet(s)
Anti-inflammatoires/composition chimique , Médicaments issus de plantes chinoises/composition chimique , Flavonoïdes/composition chimique , Hétérosides/composition chimique , Magnoliopsida/composition chimique , Animaux , Anti-inflammatoires/pharmacologie , Lignée cellulaire , Médicaments issus de plantes chinoises/pharmacologie , Flavonoïdes/pharmacologie , Hétérosides/pharmacologie , Spectrométrie de masse , Souris , Structure moléculaire , Feuilles de plante/composition chimiqueRÉSUMÉ
Fifteen epi-aleuritolic acid derivatives were synthesized and evaluated for anti-HIV activity in 293 T cells and NO production inhibition activity. Of the derivatives, 1, 2, 3, 4, 11, and 13 showed relatively potent anti-HIV activity with EC50 values ranging from 5.80 to 13.30 µM. The most potent compound, 3α-2',2'-dimethylsuccinic acyl epi-aleuritolic acid (11), displayed significant anti-HIV activity with an EC50 value of 5.80 µM. Compounds 1, 3, 4, and 11 showed NO inhibition activity, with IC50 values ranging from 3.40 to 7.10 µM and compound 1 inhibited NO production with an IC50 value of 3.40 µM.
Sujet(s)
Agents antiVIH/synthèse chimique , Agents antiVIH/pharmacologie , Monoxyde d'azote/antagonistes et inhibiteurs , Acides palmitiques/synthèse chimique , Acides palmitiques/pharmacologie , Animaux , Agents antiVIH/composition chimique , Concentration inhibitrice 50 , Mâle , Souris , Souris de lignée C57BL , Structure moléculaire , Monoxyde d'azote/biosynthèse , Acides palmitiques/composition chimiqueRÉSUMÉ
Three new tirucallane triterpenoids, brumollisols A-C (1-3, resp.), together with five known analogues, (23R,24S)-23,24,25-trihydroxytirucall-7-ene-3,6-dione (4), piscidinol A (5), 24-epipiscidinol A (6), 21α-methylmelianodiol (7), and 21ß-methylmelianodiol (8), were isolated from an EtOH extract of the stems of Brucea mollis. Their structures were elucidated by means of spectroscopic methods including 1D- and 2D-NMR techniques and mass spectrometry. In the in vitro assays, compound 6 exhibited significant cytotoxic activity against A549 and BGC-823 cancer cells with IC50 values of 1.16 and 3.01â µM, respectively. At a concentration of 10â µM, compounds 1-5, 7, and 8 were found to inhibit NO production in mouse peritoneal macrophages with inhibitory ratios ranging from 39.8±7.7 to 68.2±4.5%.
Sujet(s)
Antinéoplasiques d'origine végétale/composition chimique , Brucea/composition chimique , Triterpènes/composition chimique , Animaux , Antinéoplasiques d'origine végétale/isolement et purification , Antinéoplasiques d'origine végétale/toxicité , Survie cellulaire/effets des médicaments et des substances chimiques , Humains , Macrophages/effets des médicaments et des substances chimiques , Macrophages/métabolisme , Spectroscopie par résonance magnétique , Souris , Conformation moléculaire , Monoxyde d'azote/métabolisme , Tiges de plante/composition chimique , Triterpènes/isolement et purification , Triterpènes/toxicitéRÉSUMÉ
Four new neolignans, wilfordiols A-D (1-4), together with five known compounds (5-9), were isolated from an aqueous extract of the dried leaves of Tripterygium wilfordii. Their structures were determined by spectroscopic methods, including 1D and 2D NMR, HRESIMS, and CD experiments. The anti-inflammation activities of compounds 1-9 were evaluated by the inhibitory effect on NO production, in vitro.
Sujet(s)
Anti-inflammatoires/composition chimique , Médicaments issus de plantes chinoises/composition chimique , Lignanes/composition chimique , Tripterygium/composition chimique , Anti-inflammatoires/isolement et purification , Anti-inflammatoires/pharmacologie , Médicaments issus de plantes chinoises/isolement et purification , Médicaments issus de plantes chinoises/pharmacologie , Lignanes/isolement et purification , Lignanes/pharmacologie , Structure moléculaire , Monoxyde d'azote/antagonistes et inhibiteurs , Feuilles de plante/composition chimique , Plantes médicinales/composition chimiqueRÉSUMÉ
Five new 9,10-anthraquinones (1-5) were isolated from an ethanol extract of the roots of Knoxia valerianoides. Their structures including absolute configuration of 1 were determined by spectroscopic analysis. Compounds 4 and 5 showed moderate activity against nitrogen oxide production in macrophages induced by lipopolysaccharide, at 10(- 5) M, with inhibition ratios of 50.4 ± 3.6 and 41.7 ± 2.1%, respectively.
Sujet(s)
Anthraquinones/isolement et purification , Médicaments issus de plantes chinoises/isolement et purification , Plantes médicinales/composition chimique , Rubiaceae/composition chimique , Animaux , Anthraquinones/composition chimique , Anthraquinones/pharmacologie , Médicaments issus de plantes chinoises/composition chimique , Médicaments issus de plantes chinoises/pharmacologie , Lipopolysaccharides/pharmacologie , Macrophages péritonéaux/effets des médicaments et des substances chimiques , Souris , Structure moléculaire , Monoxyde d'azote/biosynthèse , Racines de plante/composition chimiqueRÉSUMÉ
Eight new linear polyacetylene glucosides (1-8), containing two C(10)-, one C(13)- and five C(14)-acetylenes, together with three known polyacetylenes (9-11) were isolated from the florets of Carthamus tinctorius L. Their structures were elucidated by means of spectroscopic methods and chemical evidence. The absolute configurations of compounds 3-9 were confirmed by Snatzke and Gerards's method, observing the induced circular dichroism after addition of dirhodium tetrakis (trifluoroacetate) [Rh(2)(OCOCF(3))(4)] in CHCl(3). All the isolated compounds (1-11) were also tested for inhibitory activities against LPS-induced NO production in murine macrophages and just showed weak activities at concentrations of 1×10(-5)M.