RÉSUMÉ
This study aims to screen a strain from Armillaria for the cultivation of Gastrodia elata. Specifically, Armillaria strains were isolated from different producing areas of G. elata and identified. Based on the growth characteristics of the strains and the experiment on the cultivation of G. elata, an optimal A. gallica strain was screened out. The specific process is as follows. The fungus-gro-wing materials of G. elata were collected from four producing areas and the Armillaria strains were isolated(G,Y,S,H). The strains were then identified based on morphological observation and phylogeny analysis and the commonly used strains were determined. The sucrase genotypes of the strains were identified according to our previous research findings, and the growth characteristics of the strains, such as growth rate, diameter, dry weight, and polysaccharide content of the rhizomorphs, were measured. According to the biological characteristics and sucrase genotypes, two strains were selected for the cultivation of G. elata. The tuber yield and the content of gastrodin and p-hydroxybenzyl alcohol in the tuber of G. elata were measured to select the optimal strain. The results showed that the four strains were all A. gallica. The rhizomorphs of strains G and H of the same sucrase genotype had larger/higher length, growth rate, diameter, branch number, dry weight, and polysaccharide content than those of strains S and Y of the same sucrase genotype. The tuber yield and the total content of gastrodin and p-hydroxybenzyl alcohol in tuber of G. elata cultivated with strain H were 6.528 kg·m~(-2) and 0.566%, respectively, which were 4.58 and 1.30 folds those of G. elata cultivated with strain S. Strains H and S were screened out from four strains of A. gallica based on the growth characteristics and sucrase genotype. According to the tuber yield and content of total gastrodin and p-hydroxybenzyl alcohol in the tuber of G. elata, strain H was identified as the optimal one. The findings in this study are expected to lay a basis for cultivating G. elata with high yield and quality of tubers.
Sujet(s)
Armillaria/génétique , Gastrodia , PolyosidesRÉSUMÉ
A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC50 values ranging from 4.07 µM to 9.71 µM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 µM. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent.
Sujet(s)
Antinéoplasiques , Artémisinines , Ferroptose , Humains , Cellules MCF-7 , Structure moléculaire , Antinéoplasiques/pharmacologie , Tests de criblage d'agents antitumoraux , Apoptose , Artémisinines/pharmacologie , Prolifération cellulaire , Relation structure-activité , Lignée cellulaire tumoraleRÉSUMÉ
Inosine 5'-monophosphate dehydrogenase (IMPDH; EC1.1.1.205) is the rate-limiting enzyme of GMP biosynthesis. The inhibition of IMPDH limits the growth and survival of tumors. Based on the systematic summary of clinical IMPDH inhibitors, 38 acrylamide derivatives with differently substituted indoles at the 3-position as the core scaffold were designed and synthesized. In addition, the actions of these compounds at the enzyme and cellular levels were evaluated. An MTT assay with different kinds of cells was used to assess the cytotoxic activities of compounds 14e and 14n, which displayed potent hIMPDH2 inhibitory activities (IC50 = 4.207 and 2.948 µM, respectively). Biological evaluation indicated that target compounds 14e and 14n displayed the most significant effects on SW480 human colon cancer cells (IC50 = 15.34 ± 0.06 and 15.31 ± 0.09 µM, respectively), and it was determined that these compounds are effective and valuable IMPDH inhibitors for cancer intervention.
Sujet(s)
Acrylamide , Antinéoplasiques , Humains , Acrylamide/pharmacologie , IMP dehydrogenase , Antienzymes/pharmacologie , Antinéoplasiques/pharmacologie , Indoles/pharmacologieRÉSUMÉ
Objective:To explore the effects of diverse exogenous substances at different concentrations on the growth of<italic> Polyporus umbellatus</italic> mycelium and polysaccharide content and screen out the optimal growth condition for <italic>P. umbellatus</italic> mycelium, so as to provide a reference for its large-scale artificial cultivation. Method:<italic>P. umbellatus</italic> mycelium was cultured in media containing different exogenous substances using the method for fungal culturing in plate. The growth rate of the mycelium was judged by the colony diameter and the polysaccharide content was determined by the phenol-sulfuric acid method. Result:The high-dose cyclic adenosine monophosphate, 6-benzyl aminopurine (6-BA), gibberellic acid (GA), 2,4-dichlorophenoxyacetic acid (2,4-D), vitamin (V) B<sub>1</sub>, VB<sub>3</sub>, VB<sub>6</sub>, VB<sub>9</sub>, and VB<sub>12</sub> all promoted the growth of <italic>P. umbellatus</italic> mycelium and elevated polysaccharides content. By contrast, indole acetic acid (IAA), VC, and VB<sub>2</sub> inhibited its growth, with the most obvious inhibition detected in the high-dose VC group. IAA and VB<sub>2</sub> both reduced the polysaccharide content, whereas the high-dose VC significantly increased the polysaccharide content. Cyclic adenosine monophosphate, 6-BA, GA, 2,4-D, VB<sub>1</sub>, VB<sub>3</sub>, VB<sub>6</sub>, VB<sub>9</sub>, and VB<sub>12</sub> at the concentrations of 2 mmol·L<sup>-1</sup>, 6 mg·L<sup>-1</sup>, 15 mg·L<sup>-1</sup>, 2 mg·L<sup>-1</sup>, 4 mg·L<sup>-1</sup>, 2 mg·L<sup>-1</sup>, 4 mg·L<sup>-1</sup>, 6 mg·L<sup>-1</sup>, and 10 mg·L<sup>-1</sup>, respectively, contributed to the growth of <italic>P. umbellatus</italic> mycelium<italic> </italic>and polysaccharide accumulation. Conclusion:The growth of <italic>P. umbellatus </italic>mycelium and polysaccharide accumulation can be regulated by adding exogenous substances to the culture medium.
RÉSUMÉ
Objective:To explore the feasibility of replacing wood (or wood chips) with crop residues for culturing <italic>Armillaria gallica</italic> targeting the problems of forest resource destruction and increased cultivation cost caused by the extensive use of wood in <italic>Gastrodia elata</italic> cultivation, so as to reduce the cultivation cost of <italic>G. elata</italic>, promote the effective use of crop residues, and protect forest resources. Method:The growth situation of <italic>A. gallica</italic> in different media was observed, followed by the measurement of its growth rate using streaking method and the determination of total polysaccharide content of <italic>A. gallica</italic> by phenol-concentrated sulfuric acid colorimetric method. In order to further optimize the soybean straw cultivation medium, we carried out a four-factor three-level L<sub>9</sub>(3<sup>4</sup>) orthogonal assay on the ratio of main ingredients, sucrose content, inorganic salt content, and water content. Result:The comparison of growing states of <italic>A. gallica</italic> cultured in different media revealed that <italic>A. gallica</italic> in soybean straw medium began to grow since the fourth day of inoculation, and the mycelium grew well, with the growth rate being 0.352 cm·d<sup>-1</sup>, which was 1.48 times that in birch wood medium. The total polysaccharide content of <italic>A. gallica</italic> cultured in soybean straw medium was the highest, which was 39.260 mg·g<sup>-1</sup>, much higher than 17.028 mg·g<sup>-1</sup> of that cultured in birch wood medium. This demonstrated the obvious advantage of soybean straw medium, whose main ingredients were soybean straw and wheat bran at the ratio of 8:2, with the sucrose and inorganic salt content accounting for 1% and 0.5% of the main ingredients, respectively. When the water content reached 50%, the growth rate of <italic>A. gallica</italic> was maintained at 0.392 cm·d<sup>-1</sup>. Conclusion:This study has provided a basis for utilizing soybean straw instead of wood (or wood chips) as cultivation medium for <italic>A. gallica</italic>, thus better reducing the waste of forest resources and protecting the natural environment in the cultivation of <italic>G. elata</italic>.
RÉSUMÉ
Accumulation of tau protein aggregation plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6 was initially screened by ThT fluorescence assay. Using circular dichroism and transmission electron microscopy, compound 30 showed the most potent inhibitory activity against AcPHF6 self-fibrillation. Compound 30 was further confirmed to inhibit the aggregation of full-length 2N4R tau protein by a heparin-induced mechanism. In addition, we investigated the anti-inflammatory activity of compound 30, and showed that compared with sodium usnate, it reduced NO release in LPS-stimulated mouse microglia BV2 cells. More importantly, 30 showed significant protective effects against okadaic acid-induced memory impairment in rats. Thus, 30 was a novel tau-aggregation and neuroinflammation inhibitor that represented a potential therapeutic candidate for AD.
Sujet(s)
Maladie d'Alzheimer/traitement médicamenteux , Benzofuranes/pharmacologie , Inflammation/traitement médicamenteux , Apprentissage du labyrinthe/effets des médicaments et des substances chimiques , Protéines tau/antagonistes et inhibiteurs , Maladie d'Alzheimer/métabolisme , Animaux , Benzofuranes/synthèse chimique , Benzofuranes/composition chimique , Lignée cellulaire tumorale , Modèles animaux de maladie humaine , Relation dose-effet des médicaments , Humains , Inflammation/métabolisme , Lipopolysaccharides/antagonistes et inhibiteurs , Lipopolysaccharides/pharmacologie , Mâle , Souris , Modèles moléculaires , Structure moléculaire , Monoxyde d'azote/antagonistes et inhibiteurs , Monoxyde d'azote/biosynthèse , Agrégats de protéines/effets des médicaments et des substances chimiques , Rats , Rat Sprague-Dawley , Relation structure-activité , Protéines tau/métabolismeRÉSUMÉ
Objective:As a source of energy for Armillaria mellea and Gastrodia elata,the woods species as fungus material of G.elata are diverse and play an important role in the development of G.elata industry. In order to explore the impact of different woods species on the quality of G. elata,the plant origins and lignocellulose content of the woods,the yield and quality of G. elata per unit area were systemically analyzed through literature research and investigation on production bases. Method:G. elata and its cultivated woods were collected from four main producing areas (Guizhou, Yunnan, Hubei, and Shaanxi),and the the plant origins of the woods were identified by DNA fragments. The content of lignocellulose in the woods was determined by high-performance liquid chromatography and loss-on-ignition method. The content of polysaccharides of G. elata from these 4 areas was determined by Phenol-sulfuric acid method. The yields and polysaccharide content of G. elata cultivated with different woods species were compared and their correlation with the woods was analyzed. Result:The woods as fungus material of G. elata were diverse in species, and betulaceae was the most widely used species in cultivation of G. elata. There were differences in the composition ratio of lignocellulose in the woods. Nyssaceae had the highest cellulose content,Moraceae had the highest hemicellulose content and Rosaceae had the highest lignin content. Different woods species had certain effects on the yield and polysaccharide content of G. elata. The maximum yield of G. elata was 1 285.51 g and the lowest yield was 379.30 g. The average mass fraction of polysaccharide content was 241.1 mg·g-1,with a range of 87.95-411.2 mg·g-1. The yield and polysaccharide content of G. elata were highly positively correlated with the cellulose content of the woods, and highly negatively correlated with the lignin content. Conclusion:Different woods have a significant impact on the yield and quality of G. elata. Choosing the appropriate woods species will be beneficial to the absorption of nutrients for A. mellea and the yield increase of G. elata. This study can provide a scientific basis for the selection of woods species during the cultivation of G. elata.
RÉSUMÉ
Gastrodia elata is a kind of traditional Chinese medicinal materials and has good medicinal value. G. elata is divided into five varieties, which includes G. elata f. elata(proto variant), G. elata f. glauca, G. elata f. viridis, G. elata f. flavid and G. elata f. alba. Among them, G. elata f. elata and G. elata f. glauca have excellent characteristics and higher contents of gastrodin and polysaccharides. The hybrid of G. elata f. elata and G. elata f. glauca is present in markets, but the characteristics between hybrid and parent are not obvious and distinguished quickly and accurately. The aim of this study is to establish a PCR specific PCR identification method, which can identify G. elata f. elata, G. elata f. glauca and their hybrid. Based on the re-sequencing results of G. elata, we screened for the single nucleotide polymorphism(SNP) variation sites, and designed two pairs of specific primers(W291-F/W291-R and H255-F/H255-R). We further collected G. elata f. elata, G. elata f. glauca and their hybrid samples from different regions, established and optimized PCR method, and investigated and verified their tolerance and applicability. The results showed that when the annealing temperature was 48 ℃ and the number of cycles was 33, 255 bp specific band were obtained from G. elata f. glauca and hybrid by using specific primers W291-F/W291-R. When the annealing temperature was 51 ℃ and the number of cycles was 33, 291 bp specific band were obtained from G. elata f. elata and hybrid by using specific primers H255-F/H255-R. Our method could be used as a promising method to identify G. elata f. elata, G. elata f. glauca and their hybrid.
Sujet(s)
Gastrodia , Réaction de polymérisation en chaîneRÉSUMÉ
The formation of amyloid-ß (Aß) plaques in the brain is one of the main pathological features of Alzheimer's disease (AD). The imaging probes, capable of detecting Aß deposition, are important tools for early diagnosis of AD. In this article, we designed, synthesized and evaluated a cyanine-based near-infrared fluorescence (NIRF) probe ZT-1 for the detection of Aß deposits in the brain. The probe had excellent fluorescent properties with an emission maximum above 720â¯nm upon binding to Aß aggregates with affinity of 445.0â¯nM (Kd). Furthermore, ZT-1 exhibited good biostability, photostability, and binding selectivity toward Aß1-42 aggregates by in vitro fluorescence staining experiments. In vivo NIRF imaging result also revealed that our probe could efficiently differentiate transgenic and wild-type mice. All these studies indicated that ZT-1 is a promising fluorescent probe for Aß plaques in the AD brains.
Sujet(s)
Maladie d'Alzheimer/imagerie diagnostique , Carbocyanines/composition chimique , Imagerie optique , Plaque amyloïde/composition chimique , Animaux , Carbocyanines/synthèse chimique , Relation dose-effet des médicaments , Rayons infrarouges , Mâle , Souris , Souris de lignée C57BL , Souris de lignée ICR , Structure moléculaire , Relation structure-activitéRÉSUMÉ
A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (hMAO-B). In particular, 3 and 7 showed the better inhibitory activity for hMAO-B (IC50â¯=â¯3.91⯱â¯0.23⯵M, 0.90⯱â¯0.01⯵M) respectively. Compound 3 (IC50â¯=â¯46.95⯱â¯0.21⯵M for DPPH, 1.43 and 1.74 trolox equivalent by ABTS and FRAP method respectively), and 7 (IC50â¯=â¯35.33⯱â¯0.15⯵M for DPPH, 1.70 and 1.97 trolox equivalent by ABTS method and FRAP method respectively) have excellent antioxidant effects. Cellular assay shown that 3 and 7 had lower toxicity and were resistant to neurotoxicity induced by oxidative toxins (H2O2, rotenone and oligomycin-A). More importantly, the selected compounds have neuroprotective effects against ROS generation, H2O2-induced apoptosis and a significant in vitro anti-inflammatory activity. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that 3 and 7 would be predominant to cross the blood-brain barrier. In this study, mouse microglia BV2 cells were used to establish cell oxidative stress injury model with H2O2 and to explore the protective effect and mechanism of 3 and 7. In general, 3 and 7 can be considered candidates for potential treatment of AD.
Sujet(s)
Maladie d'Alzheimer/traitement médicamenteux , Prénylation , Resvératrol/composition chimique , Animaux , Antioxydants/pharmacologie , Barrière hémato-encéphalique/métabolisme , Lignée cellulaire , Dimérisation , Humains , Souris , Monoamine oxidase/effets des médicaments et des substances chimiques , Inhibiteurs de la monoamine oxydase/composition chimique , Inhibiteurs de la monoamine oxydase/pharmacologie , Neuroprotecteurs/pharmacologie , Stress oxydatif/effets des médicaments et des substances chimiques , Rats , Resvératrol/usage thérapeutique , Relation structure-activitéRÉSUMÉ
The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC50, 0.075⯵M for eeAChE and 0.75⯵M for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50, 7.4⯵M for hMAO-B), excellent antioxidant activity (71.7⯵M of IC50 by DPPH method, 0.82 and 1.62 trolox equivalent by ABTS method and ORAC method respectively), and inhibitory effects on self-induced, hAChE-induced Aß aggregation. Moreover, 7d possessed neuroprotective potency against H2O2-induced oxidative damage on PC12â¯cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was capable of penetrating BBB and presented good liver microsomal metabolic stability. Importantly, compound 7d could dose-dependently reverse scopolamine-induced memory deficit in mice without acute toxicity. Taken together, those outstanding results highlight the donepezil-BHT hybrid 7d as a promising prototype in the research of innovative compound for AD.
Sujet(s)
Maladie d'Alzheimer/traitement médicamenteux , Antioxydants/pharmacologie , Agents cholinergiques/pharmacologie , Anticholinestérasiques/pharmacologie , Neuroprotecteurs/pharmacologie , Acetylcholinesterase/métabolisme , Maladie d'Alzheimer/métabolisme , Peptides bêta-amyloïdes/antagonistes et inhibiteurs , Peptides bêta-amyloïdes/métabolisme , Animaux , Antioxydants/synthèse chimique , Antioxydants/composition chimique , Butylhydrotoluène/composition chimique , Butylhydrotoluène/pharmacologie , Lignée cellulaire , Agents cholinergiques/synthèse chimique , Agents cholinergiques/composition chimique , Anticholinestérasiques/synthèse chimique , Anticholinestérasiques/composition chimique , Donépézil , Relation dose-effet des médicaments , Indanes/composition chimique , Indanes/pharmacologie , Souris , Structure moléculaire , Neuroprotecteurs/synthèse chimique , Neuroprotecteurs/composition chimique , Cellules PC12 , Pipéridines/composition chimique , Pipéridines/pharmacologie , Agrégats de protéines/effets des médicaments et des substances chimiques , Rats , Relation structure-activitéRÉSUMÉ
A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid-ß (Aß) aggregation and human monoamine oxidase B (hMAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5, exhibited excellent potency for inhibition of self-induced Aß1-42 aggregation (91.3±2.1%, 25µM), inhibition of hMAO-B (IC50, 1.73±0.39µM), antioxidant effects (43.4±2.6µM of IC50 by DPPH method, 0.67±0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H2O2-induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs.
Sujet(s)
Maladie d'Alzheimer/traitement médicamenteux , Conception de médicament , Imines/pharmacologie , Inhibiteurs de la monoamine oxydase/pharmacologie , Salicylates/pharmacologie , Peptides bêta-amyloïdes/antagonistes et inhibiteurs , Animaux , Survie cellulaire/effets des médicaments et des substances chimiques , Relation dose-effet des médicaments , Humains , Peroxyde d'hydrogène/pharmacologie , Imines/synthèse chimique , Imines/composition chimique , Ligands , Lipopolysaccharides/antagonistes et inhibiteurs , Lipopolysaccharides/pharmacologie , Souris , Microglie/effets des médicaments et des substances chimiques , Microglie/métabolisme , Simulation de docking moléculaire , Structure moléculaire , Monoamine oxidase/métabolisme , Inhibiteurs de la monoamine oxydase/synthèse chimique , Inhibiteurs de la monoamine oxydase/composition chimique , Cellules PC12 , Fragments peptidiques/antagonistes et inhibiteurs , Agrégats de protéines/effets des médicaments et des substances chimiques , Rats , Salicylates/synthèse chimique , Salicylates/composition chimique , Relation structure-activitéRÉSUMÉ
A series of coumarin-pargyline hybrids (4a-x) have been designed, synthesized and evaluated as novel dual inhibitors of Alzheimer's disease (AD). Most of the compounds exhibited a potent ability to inhibit amyloid-ß (Aß) aggregation and monoamine oxidases. In particular, compound 4x exhibited remarkable inhibitory activities against monoamine oxidases (IC50, 0.027 ± 0.004 µM for MAO-B; 3.275 ± 0.040 µM for MAO-A) and Aß1-42 aggregation (54.0 ± 1.1%, 25 µM). Moreover, compound 4x showed low toxicity according to in vitro cell toxicity test. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compound 4x would be potent to cross the blood-brain barrier. Collectively, these findings demonstrate that compound 4x was an effective and promising candidate for AD therapy.
Sujet(s)
Maladie d'Alzheimer/traitement médicamenteux , Peptides bêta-amyloïdes/antagonistes et inhibiteurs , Coumarines/pharmacologie , Inhibiteurs de la monoamine oxydase/pharmacologie , Monoamine oxidase/métabolisme , Pargyline/pharmacologie , Maladie d'Alzheimer/métabolisme , Peptides bêta-amyloïdes/métabolisme , Animaux , Survie cellulaire/effets des médicaments et des substances chimiques , Coumarines/composition chimique , Relation dose-effet des médicaments , Conception de médicament , Humains , Mâle , Souris , Lignées consanguines de souris , Structure moléculaire , Inhibiteurs de la monoamine oxydase/synthèse chimique , Inhibiteurs de la monoamine oxydase/composition chimique , Cellules PC12 , Pargyline/composition chimique , Agrégats de protéines/effets des médicaments et des substances chimiques , Rats , Relation structure-activitéRÉSUMÉ
ETHNOPHARMACOLOGICAL RELEVANCE: Annona muricata L. is used to treat cancer in some countries. Extracts of Annona muricata have been shown to cause apoptosis of various cancer cells in vitro, and inhibit tumor growth in vivo in animal models. However, the molecular mechanisms underlying its anti-cancer and apoptotic effects of the herb remain to be explored. AIM OF STUDY: The study investigated the molecular mechanisms underlying liver cancer cell apoptosis triggered by the ethanol extract of leaves of Annona muricata L. MATERIALS AND METHODS: Liver cancer HepG2 cells were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry and TUNEL assays were performed to confirm apoptosis. We employed functional proteomic analysis to delineate molecular pathways underlying apoptosis triggered by the herbal extract. RESULTS: We showed that the extract was able to reduce viability and trigger apoptosis of the cancer cells. Proteomic analysis identified 14 proteins associated with the extract-elicited apoptosis, which included the increased expression levels of HSP70, GRP94 and DPI-related protein 5. Western blot analysis confirmed that the extract did up-regulated the protein levels of HSP70 and GRP94. Results from bioinformatic annotation pulled out two molecular pathways for the extract, which, notably, included endoplasmic reticulum (ER) stress which was evidenced by the up-regulation of HSP70, GRP94 and PDI-related protein 5. Further examinations of typical protein signaling events in ER stress using western blot analysis have shown that the extract up-regulated the phorsphorelation of PERK and eIF2α as well as the expression level of Bip and CHOP. CONCLUSION: Our results indicate that the ethanol extract of leaves of Annona muricata L. causes apoptosis of liver cancer cells through ER stress pathway, which supports the ethnomedicinal use of this herb as an alternative or complementary therapy for cancer.
Sujet(s)
Annona/composition chimique , Antinéoplasiques d'origine végétale/pharmacologie , Protéines régulatrices de l'apoptose/métabolisme , Apoptose/effets des médicaments et des substances chimiques , Marqueurs biologiques tumoraux/métabolisme , Stress du réticulum endoplasmique/effets des médicaments et des substances chimiques , Éthanol/composition chimique , Tumeurs du foie/traitement médicamenteux , Extraits de plantes/pharmacologie , Protéomique/méthodes , Solvants/composition chimique , Antinéoplasiques d'origine végétale/isolement et purification , Survie cellulaire/effets des médicaments et des substances chimiques , Biologie informatique , Relation dose-effet des médicaments , Électrophorèse bidimensionnelle sur gel , Cellules HCT116 , Cellules HepG2 , Humains , Tumeurs du foie/métabolisme , Tumeurs du foie/anatomopathologie , Spectrométrie de masse , Phytothérapie , Extraits de plantes/isolement et purification , Feuilles de plante , Plantes médicinales , Cartographie d'interactions entre protéines , Cartes d'interactions protéiques , Transduction du signal/effets des médicaments et des substances chimiques , Facteurs tempsRÉSUMÉ
Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1) in vitro studies using cell line models; (2) serum pharmacology; (3) in vivo studies using animal models; and (4) clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time. In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance.
RÉSUMÉ
INTRODUCTION: Sepsis often causes diaphragm contractile dysfunction. Dihydropyridine receptors (DHPRα1s and DHPRα1c) and ryanodine receptors (RyR1, RyR2, and RyR3) are essential for excitation-contraction coupling in striated muscles. However, their expression in diaphragm during sepsis have not been explored. METHODS: Eight rats received endotoxin, and 8 more rats received placebo. After 24 hours, 3) diaphragm isometric contractile force was measured. The mRNA and protein levels of DHPRs and RyRs in diaphragm muscles were determined. RESULTS: Sepsis weakened diaphragm contractile function. The expression levels of DHPRα1s and RyR1 were significantly lower in septic rats than in control rats. The expression levels of DHPRα1c and RyR3 were unaffected by sepsis. RyR2 was undetectable at both mRNA and protein levels in the control and sepsis groups. CONCLUSIONS: Weakened diaphragm contraction in the septic rats was associated with reduced mRNA and protein expression of DHPRα1s and RyR1, the isoforms of skeletal muscles.
Sujet(s)
Canaux calciques de type L/métabolisme , Muscle diaphragme/métabolisme , Contraction isométrique/physiologie , Muscles squelettiques/métabolisme , Canal de libération du calcium du récepteur à la ryanodine/métabolisme , Sepsie/métabolisme , Animaux , Canaux calciques de type L/biosynthèse , Signalisation calcique/effets des médicaments et des substances chimiques , Signalisation calcique/physiologie , Muscle diaphragme/effets des médicaments et des substances chimiques , Muscle diaphragme/physiopathologie , Modèles animaux de maladie humaine , Régulation négative/effets des médicaments et des substances chimiques , Régulation négative/physiologie , Contraction isométrique/effets des médicaments et des substances chimiques , Mâle , Muscles squelettiques/effets des médicaments et des substances chimiques , Isoformes de protéines/effets des médicaments et des substances chimiques , Isoformes de protéines/métabolisme , ARN messager/antagonistes et inhibiteurs , ARN messager/métabolisme , Rats , Canal de libération du calcium du récepteur à la ryanodine/biosynthèse , Sepsie/induit chimiquement , Sepsie/physiopathologie , Choc septique/métabolisme , Choc septique/physiopathologieRÉSUMÉ
AIM: To investigate the prevalence and risk factors of polypoid lesions of gallbladder (PLG) among the health examinees in the Shanghai region, China. METHODS: A total of 11,816 subjects who underwent health examinations in our hospital between August 2010 and February 2011 were analyzed retrospectively. Among them, there were 7174 men and 4642 women. PLG was diagnosed by the real-time ultrasonography. Those with the body mass index (BMI) ≥ 28 were considered to be obese. Blood biochemical indices were detected with the fully automatic biochemical analyzer and hepatitis B surface antigen (HBsAg) was tested by the automated enzyme immunoassay. The correlations between the prevalence of PLG and age, sex, BMI, serum cholesterol (T-Cho), triglycerides (TG), blood sugar, HBsAg, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), gallstone and fatty liver were investigated. After univariate analysis of 11 variables, stepwise logistic regression analysis was performed to explore the risk factors of PLG. RESULTS: There was a significant difference in sex, T-Cho, HBsAg, HDL-C, LDL-C and fatty liver between the PLG-positive group and the PLG-negative group (332/163 vs 6842/4479, P = 0.003; 22/473 vs 295/11,026, P =0.013; 92/403 vs 993/10,328, P = 0.001; 47/448 vs 332/10,989, P = 0.001; 32/463 vs 381/10,940, P = 0.001; 83/412 vs 3260/8061, P = 0.001). No significant difference was found in the age, BMI, TG, blood sugar and gallstone between the two groups (47.3 ± 26 vs 45.1 ± 33, P = 0.173; 59/436 vs 1097/10,224, P = 0.102; 52/443 vs 982/10,339, P = 0.158; 17/478 vs 295/11,026, P = 0.26; 24/471 vs 395/10,926, P = 0.109). Logistic regression analysis showed that the sex, HBsAg and HDL-C were independent risk factors for the development of PLG in a descending order of HDL-C > HBsAg > sex. CONCLUSION: In healthy people, the male gender, positive HBsAg, and low HDL-C confer higher risks of PLG development.
Sujet(s)
Maladies de la vésicule biliaire/épidémiologie , Polypes/épidémiologie , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Chine/épidémiologie , Femelle , Humains , Mâle , Adulte d'âge moyen , Facteurs de risque , Jeune adulteRÉSUMÉ
<p><b>OBJECTIVE</b>To evaluate the long-term protective effects of hepatitis B vaccine after immunizing to the children for 12 years in Beijing.</p><p><b>METHODS</b>The multiple stratified cluster sampling was used in this epidemiological survey. The sampling children's blood serum HBsAg, anti-HBs and anti-HBc were checked and measured by the solid phase radioimmunoassay (SPRIA). The serological level of these index and the causes of the children with HBsAg positive were analyzed.</p><p><b>RESULTS</b>There were 2,419 cases 3-12 years-old children immunized with the hepatitis B vaccine in infant period were surveyed and the total HBsAg positive rate was 0.52%. The vaccine protective rate was 88.45% (95% CI: 65.67%-97.89%). The total anti-HBc positive rate was 2.21%, being no statistical significance among the age groups. The average anti-HBs positive rate of 3-6 years-old children immunized with gene recombining vaccine was 38.79% and descending greatly following the age's dropping. The geometric means of anti-HBs serological titer (GMT) was 52.83 mIU/ml, showing no statistical significance among the age groups. The average anti-HBs positive rate of 6-12 years-old children immunized with the blood rooting vaccine was 50.79%. The geometric means of anti-HBs serological titer (GMT) was 61.51 mIU/ml. There were no statistical significances among the age groups. Among the HBsAg positive children, more than 50% of the children's mothers were HBsAg positive also.</p><p><b>CONCLUSIONS</b>The protective effects given by immunization were significant after the hepatitis B vaccine vaccination for 12 years in Beijing. The booster immunization was not necessary, because the HBsAg positive rate didn't ascend obviously as the immunization time prolonging. As the anti-HBs positive rate of children who were immunized by the gene recombining vaccine might be descending following the age's dropping greatly, we should strengthen the serological surveillance of hepatitis B. The main cause that the children became the HBsAg carrier should be a vertical transmission.</p>
Sujet(s)
Enfant , Enfant d'âge préscolaire , Humains , Chine , Épidémiologie , Études de suivi , Hépatite B , Épidémiologie , Allergie et immunologie , Anticorps de l'hépatite B , Sang , Antigènes de surface du virus de l'hépatite B , Sang , Vaccins anti-hépatite B , Allergie et immunologie , Utilisations thérapeutiques , Virus de l'hépatite B , Allergie et immunologie , Immunité activeRÉSUMÉ
<p><b>OBJECTIVE</b>To evaluating the epidemiological effect after hepatitis B immunization among youngsters in Beijing.</p><p><b>METHODS</b>A multistage sampling method was used for data collection from immunization cards, reports on field epidemiological survey on hepatitis B virus (HBV) immunization of youngsters and the analysis of infectious diseases. HBsAg, anti-HBs and anti-HBc levels were detected by solid phase radioimmunoassays (SPRIA).</p><p><b>RESULTS</b>The average incidence rates of hepatitis B in 10 - 19 years-olds prior to HBV immunization was 12.11-16.89/100 000, while declined to 1.78-10.95/100 000 (chi(2) = 10.71 - 60.45, P < 0.01). HBsAg carrying rate of the youngsters decreased from 6.34% to 1.37% (80.00%) after vaccination (chi(2) = 14.16, P < 0.01).</p><p><b>CONCLUSION</b>Hepatitis B vaccination among youngsters is an effective measure for the prevention and control of hepatitis B virus infection.</p>