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Grain-sized moxibustion (GS-Moxi) and suspended moxibustion (S-Moxi) represent the two typical local heat therapies in Traditional Chinese Medicine (TCM) and have been extensively used in treating gastric ulcers (GU) in China. However, the difference in biological response between the two moxibustion therapies in treating GU remains unclear. Here we investigated the therapeutic effect and potential mechanistic difference underlying the two moxibustion methods. Ethanol-induced GU model was established and was treated with GS-Moxi or S-Moxi at ST36 and ST21 for 5 days separately. And then, gastric histopathological examination, immunohistochemical staining for repair factors (EGFR, VEGF, Ki67), and 1H NMR-based metabolomics analysis of plasma and stomach of rats were conducted. We found GS-Moxi and S-Moxi effectively alleviated gastric damage and significantly increased the expression of related repair factors. However, S-Moxi corrected aberrant energy metabolism and lipids metabolism in GU rats but had little effect on neurotransmitter-related metabolism, while GS-Moxi regulated energy metabolism and neurotransmitter-related metabolism in GU rats but had no effect on lipids metabolism. We further proposed that the main target of S-Moxi may be liver and vasculature, whereas GS-Moxi specially targeted the stomach via regulating nervous system. This study strongly verified the outstanding gastroprotective effects of moxibustion and enriched our understanding of the varied biological responses triggered by different moxibustion methods.
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Cold is a major environmental factor that restrains potato production. Abscisic acid (ABA) can enhance freezing tolerance in many plant species, but powerful evidence of the ABA-mediated signalling pathway related to freezing tolerance is still in deficiency. In the present study, cold acclimation capacity of the potato genotypes was enhanced alongside with improved endogenous content of ABA. Further exogenous application of ABA and its inhibitor (NDGA) could enhance and reduce potato freezing tolerance, respectively. Moreover, expression pattern of downstream genes in ABA signalling pathway was analysed and only ScAREB4 was identified with specifically upregulate in S. commersonii (CMM5) after cold and ABA treatments. Transgenic assay with overexpression of ScAREB4 showed that ScAREB4 promoted freezing tolerance. Global transcriptome profiling indicated that overexpression of ScAREB4 induced expression of TPS9 (trehalose-6-phosphate synthase) and GSTU8 (glutathione transferase), in accordance with improved TPS activity, trehalose content, higher GST activity and accumulated dramatically less H2 O2 in the ScAREB4 overexpressed transgenic lines. Taken together, the current results indicate that increased endogenous content of ABA is related to freezing tolerance in potato. Moreover, ScAREB4 functions as a downstream transcription factor of ABA signalling to promote cold tolerance, which is associated with increased trehalose content and antioxidant capacity.
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Solanum tuberosum , Solanum tuberosum/genética , Trealose , Congelamento , Aclimatação/fisiologia , Ácido Abscísico/farmacologia , Estresse Oxidativo , Regulação da Expressão Gênica de PlantasRESUMO
Cholestasis is a common clinical disease caused by a disorder in bile acids (BAs) homeostasis, which promotes its development. The Farnesoid X receptor (FXR) plays a critical role in regulating BAs homeostasis, making it an essential target for cholestasis treatment. Although several active FXR agonists have been identified, effective drugs for cholestasis are still lacking. To address this, a molecular docking-based virtual screening method was used to identify potential FXR agonists. A hierarchical screening strategy was employed to improve the screening accuracy, and six compounds were selected for further evaluation. Dual-luciferase reporter gene assay was used to demonstrate FXR activation by the screened compounds, and their cytotoxicity was then evaluated. Among the compounds, licraside showed the best performance and was selected for in vivo evaluation using an ANIT-induced cholestasis animal model. Results demonstrated that licraside significantly reduced biliary TBA, serum ALT, AST, GGT, ALP, TBIL, and TBA levels. Liver histopathological analysis showed that licraside also had a therapeutic effect on ANIT-induced liver injury. Overall, these findings suggest that licraside is an FXR agonist with potential therapeutic effects on cholestasis. This study provides valuable insights into the development of novel lead compounds from traditional Chinese medicine for cholestasis treatment.
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AIM: This study aimed to investigate the effects of maternal critical care simulation training on the core competency and satisfaction of midwives in China. BACKGROUND: Midwives play an important role during the peripartum period. Simulation-based training could be an effective tool in improving the core competency of midwives when managing critical obstetric illnesses. DESIGN: A pilot pre- and post-course, quasi-experimental study in China. METHOD: In July 2022, 82 midwives completed a 2-day obstetric critical care simulation training and survey. Core competency was evaluated by a comprehensive score system, including response ability, communication ability, site control ability, critical thinking ability, team cooperation ability, forward-thinking ability, midwifery specialty ability, and error correction ability. We used the Simulation Effectiveness Tool-Modified (SET-M) to evaluate the learning experience and satisfaction. Descriptive analysis, McNemar χ2 test, and subject content analysis were used for data analysis. RESULTS: After the training, the core competency scores showed significant improvements in the case scenarios simulating shoulder dystocia, amniotic fluid embolism, and eclampsia (P < 0.05) but not postpartum hemorrhage (P > 0.05). The scores evaluated by the SET-M were all above 2.5 points. Some midwives preferred extended course duration, expanded course materials, and more active involvement in the simulation exercises. The midwives were generally highly satisfied with the training, but some expressed certain negative emotions, such as anxiety and nervousness. CONCLUSION: The high quality of scientifically constructed and implemented obstetric critical care simulation training courses could improve the core competency and satisfaction of midwives. Appropriate preparation and professional simulation teachers are required to reduce negative emotions and improve learning outcomes and experience.
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Tocologia , Hemorragia Pós-Parto , Treinamento por Simulação , Gravidez , Feminino , Humanos , Tocologia/educação , Aprendizagem , Cuidados CríticosRESUMO
Peptic ulcer disease (PUD) is a common disease and frequently encountered in the clinic. Accumulating evidence suggests that PUD is associated with the gastrointestinal microbiota. Electroacupuncture (EA) is an improved version of acupuncture, which can improve the clinical effect by increasing the stimulation and delivering appropriate electrical pulses to needles. This method has been widely used in the treatment of peptic ulcer disease. However, its effect on gastrointestinal microbiota remains unclear. Therefore, in the present study, the ameliorative effect of EA was evaluated on the gastroduodenal mucosa, and the regulatory effect of the gastroduodenal microbiota was assessed in PUD mice. A total of 48 male Kun Ming mice were randomly divided into the following groups: normal control group (NC), PUD model group (PUD), Shousanli group (LI10), and Zusanli group (ST36) (n=12). The mice in groups LI10 and ST36 were treated with EA at LI10 and ST36, respectively. This intervention was continued for 7 days. Subsequently, we evaluated the morphological changes in the gastric and duodenal mucosa, and specific indices were measured, including the contents of serum dopamine (DA), the trefoil factor (TFF), and the vasoactive intestinal peptide (VIP). In addition, the gastric and duodenal microbiota were assessed via 16S ribosomal DNA sequencing. The results indicated that EA at LI10 or ST36 significantly reduced the injury of the gastroduodenal mucosa in PUD mice. The gastric microbial community structure of the groups LI10 and ST36 was similar to that of the NC group following comparison with the microbial community structure of the PUD model group. Moreover, the abundance of Firmicutes in the stomach was decreased, whereas that of Bacteroidetes was increased, and the abundance of Firmicutes in the duodenum was decreased. Furthermore, the microbial diversity and richness of the gastric microbiota in group LI10 were also significantly increased, and the serum dopamine and trefoil factor levels in group ST36 were significantly increased. Therefore, it is suggested that EA ameliorating PUD is in association with improving the levels of DA and TFF and regulating the relative abundances of Firmicutes and Bacteroidetes in the gastric microbiota.
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Eletroacupuntura , Microbioma Gastrointestinal , Úlcera Péptica , Fatores Trefoil , Animais , Dopamina , Masculino , Camundongos , Úlcera Péptica/terapiaRESUMO
As per the theory of traditional Chinese medicine (TCM), the liver and kidney dysfunction are important pathogenies for premature ovarian failure (POF). POF is a common gynecological disease that reduced the pregnancy rate. Electro-acupuncture (EA) is a useful non-pharmaceutical therapy that supposedly regulates the function of the liver and kidney in the treatment of POF with TCM. However, the underlying mechanism of EA in the treatment of POF has not been adequately studied through metabonomics with reference to the theory of TCM. Accordingly, we investigated the effect of EA on the liver and kidney metabolites in POF mice through metabolomics. POF mice were established via intraperitoneal injection of cisplatin. Both Sanyinjiao (SP6) and Guanyuan (CV4) were stimulated by EA for 3 weeks. The biological samples (including the serum and the ovary, liver, and kidney tissues) were evaluated by histopathology, molecular biology, and hydrogen-1 nuclear magnetic resonance (1HNMR)-based metabolomics to assess the efficacy of EA. 1HNMR data were analyzed by the orthogonal partial least squares discriminant analysis (OPLS-DA). The results revealed that EA was beneficial to ovarian function and the menstrual cycle of POF. Both the energy metabolism and neurotransmitter metabolism in the liver and kidney were regulated by EA. Notably, EA played an important role in regulating energy-related metabolism in the kidney, and the better effect of neurotransmitter-related metabolism in the liver was regulated by EA. These findings indicated that the ovarian functions could be improved and the metabolic disorder of the liver and kidney caused by POF could be regulated by EA. Our study results thus suggested that the EA therapy, based on the results for the liver and kidney, were related to POF in TCM, as preliminarily confirmed through metabolomics.
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Terapia por Acupuntura , Doenças Metabólicas , Insuficiência Ovariana Primária , Animais , Feminino , Humanos , Rim , Fígado/patologia , Camundongos , Neurotransmissores , Insuficiência Ovariana Primária/patologia , Insuficiência Ovariana Primária/terapiaRESUMO
Growing evidence showed that the gut microbiota was associated with premature ovarian failure (POF). Many clinical types of research had shown that electroacupuncture was effective in the treatment of POF. However, there was little research on regulating the gut microbiome of POF mice by electroacupuncture. Therefore, this study attempted to verify whether electroacupuncture could regulate the gut microbiome in POF mice. POF mice were established by being injected intraperitoneally with cisplatin (2 mg/kg) for 2 weeks. Guanyuan (CV4) and Sanyinjiao (SP6) were selected in the electroacupuncture-at-the-acupoints group (EA group). Nonacupoints around CV4 and SP6 were selected in the electroacupuncture-at-the-nonacupoints group (EN group). The EA group and EN group were treated for 3 weeks. The ovarian function was evaluated by histopathological and molecular assays. Meanwhile, the gut microbiome of all mice was detected by 16S rDNA sequencing. The results showed that EA could restore the estrous cycle and reduce the number of atresia follicles in POF mice. The levels of serum follicle-stimulating hormone and luteinizing hormone were decreased by EA. As well, the levels of serum estradiol, anti-Mullerian hormone, and ß-glucuronidase were increased by EA. The relative expressions of PI3K, AKT, and mTOR were increased to promote the proliferation of ovarian cells in the EA group. According to the results of 16S rDNA sequencing, the abundance and diversity of the gut microbiome could be regulated by EA. The relative abundance of beneficial bacteria was increased by EA. The KEGG pathway analysis showed that the gut microbiome associated with the estrogen signaling pathway, oocyte maturation, and PI3K-AKT signaling pathway was regulated by EA.
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Microbial application is an efficient, economical, and ecofriendly method for remediating black-odorous rivers. In this study, the field treatment effect and microbial community changes were monitored during remediation by the acclimated complex microorganisms of a typical black-odorous stream. After the treatment, the total phosphorus and ammonia contents decreased by 74.0% and 76.3% and the concentrations of dissolved oxygen increased from 1.65 to 4.90 mg/L, indicating the effectiveness of the acclimated composite microorganisms. The proportion of Bacteroidetes decreased significantly by 48.1% and that of Firmicutes increased by 2.23% on average, and the microbial diversity index first increased and then tended to be uniform. Redundancy analysis demonstrated that the pH, dissolved oxygen, and oxidation-reduction potential together determined the composition of the microbial communities (p < 0.05). These findings showed that the acclimated composite microorganisms can effectively remediate the black odor.
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Microbiota , Rios , Odorantes , FósforoRESUMO
Lagotis brachystachya Maxim (L. brachystachya) is an herb widely used in traditional Tibetan medicine. In the present study, the antibacterial activity of L. brachystachya extract to extended-spectrum-lactamases (ESBLs)-producing E. coli was determined by Kirby-Bauer disc diffusion, minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) methods as well as time-kill curve assay. Meanwhile, the biofilm inhibition and eradication effects of L. brachystachya extract on the ESBLs-producing E. coli were evaluated by crystal violet staining, and further confirmed by confocal laser scanning microscope (CLSM) and scanning electron microscopy (SEM). The results indicated that L. brachystachya extract exhibited moderate antibacterial activity, with diameter of inhibition zones varying from 15.4 to 20.3 mm, and the MIC and MBC values were 6.25 to 25 mg/mL and 12.5 to 100 mg/mL, respectively. Time-kill curve showed that 4 × MIC level of L. brachystachya extract concentration of was able to kill 99.9% of ESBLs-producing E. coli after 16 h treatment. The biofilm inhibition rate and eradication rate for the ESBLs-producing E. coli were 35.66 to 79.91% and 22.18 to 56.21% at MIC level of extract concentration, respectively. CLSM images showed that the biofilm became thinner as the ESBLs-producing E. coli isolate exposed to L. brachystachya extract with a concentration-dependent manner from 1/4 × MIC to MIC compared with the control isolate. SEM images indicated that L. brachystachya extract at 1/2 × MIC and MIC levels could evidently inhibit the biofilm formation or eradicate the mature biofilms. The effect of L. brachystachya highlights its potential of antibacterial and antibiofilm activities against the ESBLs-producing E. coli.
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Antibacterianos , Biofilmes/efeitos dos fármacos , Infecções por Escherichia coli , Extratos Vegetais , Plantaginaceae/química , Animais , Antibacterianos/farmacologia , Galinhas , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Extratos Vegetais/farmacologia , beta-LactamasesRESUMO
Synergistic phototherapy provides a promising strategy to conquer the hypoxia and heterogeneity of tumors and realize a better therapeutic effect than monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). The development of efficient multifunctional organic phototheranostic systems still remains a challenging task. Herein, 9,10-phenanthrenequinone (PQ) with strong electron-withdrawing ability is conjugated with the rotor-type electron-donating triphenylamine derivatives to create a series of tailor-made photosensitizers. The highly efficient Type I reactive oxygen species generation and outstanding photothermal conversion capacity are tactfully integrated into these PQ-cored photosensitizers. The underlying photophysical and photochemical mechanisms of the combined photothermal and Type I photodynamic effects are deciphered by experimental and theoretical methods and are closely associated with the active intramolecular bond stretching vibration, facilitated intersystem crossing, and specific redox cycling activity of the PQ core. Both in vitro and in vivo evaluations demonstrate that the nanoagents fabricated by these PQ-based photosensitizers are excellent candidates for Type I photodynamic and photothermal combined antitumor therapy. This study thus broadens the horizon for the development of high-performance PTT/Type I PDT nanoagents for synergistic phototheranostic treatments.
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Nanopartículas , Fotoquimioterapia , Fenantrenos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Terapia FototérmicaRESUMO
BACKGROUND: Stress ulcer (SU) is a serious gastrointestinal mucosal lesion under acute stress. Huanglian decoction is a famous traditional Chinese medicine prescription, which has been used to treat digestive system diseases for thousands of years. Many clinical cases have proved that Huanglian decoction has a good effect on SU. Some studies have shown that the intestinal bacteria will be changed accordingly when the gastrointestinal mucosa is damaged. However, there are few published reports on the effect of the intestinal microbiome with SU mice that were treated by Huanglian decoction. In this study, we investigated the effect of the fecal microbiome in mice with SU by the 16S rDNA sequencing technology. METHODS: Male KM mice were induced by cold-restraint stress except for the normal control group and then treated by Huanglian decoction (Group HD) and Esomeprazole magnesium solution (Group ES) separately for 7 days. 16S rDNA sequencing technology analysis was applied to evaluate the changes of bacterial flora in mice feces. And, histopathological methods and molecular biological detection methods were also performed. RESULTS: Huanglian decoction could help to repair the gastric mucosal injury and regulate the relative content of TNF-α and IL-1ß. Moreover, Huanglian decoction could increase the relative abundance of intestinal probiotics in the intestine of mice with SU, especially in Verrucomicrobiae and Akkermansia. CONCLUSIONS: Huanglian decoction might effectively promote the repair of gastrointestinal mucosal injury and regulate the number and species of intestinal bacteria to maintain the stability of gastrointestinal microecology.
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OBJECTIVE: This study was designed to evaluate the effects of yixintongmai on proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) cultured with high glucose. METHODS: VSMCs of the thoracic aorta from 5- to 8-week-old male Sprague-Dawley rats were cultured with normal (4.5 mM) or high (25 mM) glucose, respectively. The concentration of yixintongmai powder at 360 µg/ml was chosen according to pre-experimental results. RESULTS: Yixintongmai inhibited the proliferation of VSMCs (CCK-8 assay: 0.75 ± 0.04 versus 0.98 ± 0.09 OD, P < 0.001; cell counting: 37533 ± 1861 versus 56009 ± 3779 cells/well, P < 0.001) and the expression of proliferating cell nuclear antigen (0.74 ± 0.08 fold, P < 0.001) as compared with high glucose (HG). Yixintongmai inhibited the migration of VSMCs (transwell assay: 146 ± 16 versus 265 ± 62 cells; P < 0.001), scratch wound assay (0.17 ± 0.01 fold, P < 0.001), and the expression of matrix metalloproteinases-9 (0.87 ± 0.03 fold, P < 0.001) as compared with HG. Yixintongmai decreased mitochondrial membrane potentials (0.36 ± 0.12 fold, P < 0.001) and promoted early (2.11 ± 0.20 fold, P < 0.01) and late (2.11 ± 0.28 fold, P < 0.01) apoptosis of VSMCs as compared with HG. Yixintongmai inhibited the expression of B-cell lymphoma 2 (0.83 ± 0.07 fold, P < 0.01) and stimulated the activity of cleaved-capase-3/caspase-3 (2.00 ± 0.12 fold, P < 0.05) as compared with HG. Yixintongmai inhibited reactive oxygen species generation (0.46 ± 0.03 fold, P < 0.01) and the expression of NADPH oxidase-1 (0.84 ± 0.04 fold, P < 0.001), nuclear factor-kappa B (NF-κB) p65 (0.71 ± 0.07 fold, P < 0.001), phosphorylated NF-κB p65 (0.39 ± 0.02 fold, P < 0.0001), and inhibited nuclear translocation of NF-κB p65 (0.87 ± 0.03 fold, P < 0.001) in VSMCs as compared with HG. CONCLUSIONS: Yixintongmai inhibits the proliferation and migration and promotes the apoptosis of VSMCs cultured with HG, which suggests the potential anti-atherosclerotic effects of this traditional Chinese medicine.
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Multimodal therapy is attracting increasing attention to improve tumor treatment efficacy, but generally requires various complicated ingredients combined within one theranostic system to achieve multiple functions. Herein, a multifunctional theranostic nanoplatform based on a single aggregation-induced-emission luminogen (AIEgen), DDTB, is designed to integrate near-infrared (NIR) fluorescence, photothermal, photodynamic, and immunological effects. Intravenously injected AIEgen-based nanoparticles can efficiently accumulate in tumors with NIR fluorescence to provide preoperative diagnosis. Most of the tumors are excised under intraoperative fluorescence navigation, whereafter, some microscopic residual tumors are completely ablated by photodynamic and photothermal therapies for maximally killing the tumor cells and tissues. Up to 90% of the survival rate can be achieved by this synergistic image-guided surgery and photodynamic and photothermal therapies. Importantly, the nanoparticles-mediated photothermal/photodynamic therapy plus programmed death-ligand 1 antibody significantly induce tumor elimination by enhancing the effect of immunotherapy. This theranostic strategy on the basis of a single AIEgen significantly improves the survival of cancer mice with maximized therapeutic outcomes, and holds great promise for clinical cancer treatment.
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Fotoquimioterapia , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Humanos , Hipertermia Induzida , CamundongosRESUMO
Anticardiolipin antibody (aCL), an important characterization of antiphospholipid syndrome, shows an intense association with vascular endothelial injury. Hyperoside is a flavonoid extracted from medicinal plants traditionally used in Chinese medicines, displaying anti-inflammatory, anti-cancer, and anti-oxidative properties in various diseases. Recent studies have shifted the focus on the protective effects of hyperoside on vascular endothelial injury. However, little is known about the mechanisms involved. In the present study, we investigated the effect of hyperoside on aCL-induced injury of human umbilical vein endothelial cells (HUVECs) in vitro. Our data illustrated that aCL induced HUVEC injury via inhibiting autophagy. Hyperoside reduced aCL-induced secretion of proinflammatory cytokines IL-1ß and IL-8 and endothelial adhesion cytokines TF, ICAM1, and VCAM1 in HUVECs. Additionally, hyperoside activated autophagy and suppressed the mTOR/S6K and TLR4/Myd88/NF-κB signaling transduction pathways in aCL-induced HUVECs. To the best of our knowledge, this is the first study to investigate the effect of hyperoside on aCL-induced injury, as well as offer insights into the involved mechanisms, which is of great significance for the treatment of antiphospholipid syndrome.
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ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg (Sanyeqing) is traditionally used as a folk medicine for the treatments of inflammation, high fever, hepatitis and cancer, and can improve the immune function of the patient. It belongs to the family of Vitaceae, and is mainly distributed in southeast China (Yunnan province) and can be found in India (Andaman Islands), Myanmar, Thailand, Vietnam, Malaysia and Indonesia in the valleys with 1100-1300 m above the sea level. AIM OF THE STUDY: The present study aimed to characterize the chemical properties of a purified polysaccharide extracted from the aerial part of Tetrastigma hemsleyanum (SYQP) and investigate its antipyretic and antitumor effects in mice models. MATERIALS AND METHODS: Water-soluble crude polysaccharides from the aerial parts of Tetrastigma hemsleyanum were extracted and fractionated by DEAE and gel permeation chromatography. Homogeneity, molecular weight, monosaccharide composition, and FTIR analysis were performed to characterize the SYQP. Antipyretic effect of SYQP was examined using Brewer's yeast induced hyperthermia test. Antitumor effect was investigated using H22 tumor bearing mice. The serum cytokines were determined to evaluated the biological activities of SYQP. RESULTS: SYQP was composed of galacturonic acid (GalA), glucose (Glc), mannose (Man), arabinose (Ara), galactose (Gal), and rhamnose (Rha) with a molar ratio of 11.3:7.1:2.5:1.0:0.9:0.5 and it had an average molecular weight of 66.2 kDa. The oral administration of SYQP at 200 and 400 mg/kg could markedly suppress the hyperthermia of mice induced by Brewer's yeast and decrease the production of cytokines especially prostaglandin E2 (PGE2) in the serum of mice. SYQP inhibited the growth of H22 tumor in mice with inhibitory rate of 39.9% at the administration dose of 200 mg/kg and increased the production of cytokines such as tumor necrosis factor-alpha (TNF-a) and interferon γ (IFN-γ). Experimental results showed that the preventive administration of SYQP before lipopolysaccharide (LPS) reduced the high cytokine levels such as IL-6, IL-10 and IFN-γ, indicating that SYQP might act as a competitor with LPS to interact with toll like receptor 4 (TLR4), which further regulated the secretion of cytokines. CONCLUSION: The anti-inflammatory and antitumor activities of SYQP might be related to its regulation of host immune function by controlling the secretion of cytokines.
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Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Antipiréticos/uso terapêutico , Hipertermia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Polissacarídeos/uso terapêutico , Vitaceae , Animais , Linhagem Celular , Citocinas/sangue , Dinoprostona/sangue , Humanos , Hipertermia/induzido quimicamente , Lipopolissacarídeos , Linfócitos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Componentes Aéreos da Planta , Saccharomyces cerevisiae , Baço/citologia , Carga Tumoral/efeitos dos fármacosRESUMO
Two new lignans (1-2), along with five known compounds (3-7) with different structures were isolated from leaves and twigs of Cleistanthus concinnus Croizat. The new lignans were elucidated as (7'R,8'S)-3,3',5'-trimethoxy-4,4'-dihydroxy-7-en-7',9- epoxy-8,8'-lignan (1) and (7'R,8'S)-3,3'-dimethoxy-4,4'-dihydroxy-7-en-7',9-epoxy-8, 8'-lignan (2) by comprehensive spectroscopic analysis including 1D and 2D NMR as well as HREIMS and comparing their NMR data with known compounds in the literature. Among these isolated compounds, compound 1, 2, 3, and 6 were tested for anti- inflammatory effects by inhibiting NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Compound 1, 2, and 6 exhibit NO inhibitory activity.[Formula: see text].
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Euphorbiaceae/química , Lignanas/química , Lignanas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , China , Avaliação Pré-Clínica de Medicamentos , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Folhas de Planta/química , Células RAW 264.7RESUMO
Aim: To investigate the anticancer effects of Jinlong capsule (JLC) against human glioblastoma cells and the possible underlying mechanism. Methods: Cell Counting Kit-8 and colony formation assay were adopted for the analysis of cell viability. Cell invasion and migration were evaluated by transwell and wound healing assays. Then, the expression level of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), S6 and phosphorylated S6 (p-S6) were determined by western blotting. Results: The results showed that JLC significantly inhibited human glioblastoma cell proliferation, invasion and migration in a dose-dependent manner. The expressions of p-mTOR and p-S6 were dramatically suppressed by JLC. Furtherly, inhibition of mTOR reduced the cell migration and invasion, while the mTOR agonist (MHY1485) could partially reverse the anti-migration and anti-invasion activity of JLC. Conclusion: The above results suggested that JLC would be a potential candidate for the treatment of glioblastoma.
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Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Glioblastoma/tratamento farmacológico , Invasividade Neoplásica , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases S6 Ribossômicas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/química , Cápsulas/química , Cápsulas/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Due to the outstanding synergistic effects and low-toxicity, combination therapy exhibits more considerable potential in antitumor activity than monotherapy. Herein, a core-shell magnetic gold nanostar (Fe3O4@GNS, MGNS)-based system for codelivery of a mitochondrial targeting amphipathic tail-anchoring peptide (ATAP) and a membrane-associated cytokine (tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) was constructed. The magnetic core can facilitate delivery of the drug vehicle by external magnetic field, which results in accurate accumulation and enhances tumor cellular uptake for preliminary targeting. TRAIL and ATAP could sequentially target and be released toward the plasma membrane and mitochondria, initiating the extrinsic and intrinsic apoptosis pathways, respectively. The gold shell of MGNS can cause local tumor hyperthermia due to broad-band plasmon resonances in the near-infrared region, which can act as a complement with the peptide drug to further enhance apoptosis. Both in vitro and in vivo experiments revealed that rationally integrating extrinsic apoptosis, intrinsic apoptosis and hyperthermia for triplexed synergistic therapy, enabled the smart drug vehicle with pinpoint peptide drug delivery capabilities, and minimized side effects, enhancing the antitumor efficiency.
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Ouro/química , Magnetismo , Nanoestruturas/química , Peptídeos/química , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Portadores de Fármacos/química , Óxido Ferroso-Férrico/química , Células HeLa , Humanos , Hipertermia Induzida , Raios Infravermelhos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oligopeptídeos/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Ligante Indutor de Apoptose Relacionado a TNF/química , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Two new sesquiterpenoids were isolated from Stellera chamaejasme L., known as the traditional Chinese herb 'Rui Xiang Lang Du'. The compounds were elucidated as stelleraguaianone B (1) and C (2) by comprehensive spectroscopic analysis, including 1D and 2D NMR as well as HRESIMS, and by comparing their NMR data with known compounds. In addition, the structure of 1 was further confirmed by single-crystal X-ray diffraction analysis. Both the compounds were evaluated for their cytotoxicity on common tumour cell lines in vitro, which revealed that compound 1 exhibits cytotoxic activity on A549 cells, while 2 has no activity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Sesquiterpenos/farmacologia , Thymelaeaceae/química , Células A549 , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Sesquiterpenos/isolamento & purificaçãoRESUMO
Candidatus Accumulibacter has been identified as dominant polyphosphate-accumulating organisms (PAOs) in enhanced biological phosphorus (P) removal (EBPR) from wastewater. This study revealed the relevance of community structure, abundance and seasonal population dynamics of Candidatus Accumulibacter to process operation of wastewater treatment plants (WWTPs) in China using ppk1 gene as phylogenetic marker. All sludge samples had properties of denitrifying P removal using nitrate as an electron acceptor. Accumulibacter abundance in the anaerobic-anoxic-oxic (A2O) process was the highest (26% of total bacteria), and higher in winter than in summer with a better EBPR performance. Type-II was the dominant Accumulibacter in all processes, and type-I accounted for a small proportion of total Accumulibacter. The abundance of Clade-IIC as the most dominant clade reached 2.59×109 cells/g MLSS and accounted for 87.3% of total Accumulibacter. Clade IIC mainly contributed to denitrifying P removal. Clades IIA, IIC and IID were found in all processes, while clade-IIF was only found in oxidation ditch process through phylogenetic analysis. High proportion of clade IID to total Accumulibacter led to poor performance of aerobic P-uptake in inverted A2O process. Therefore, Accumulibacter clades in WWTPs were diverse, and EBPR performance was closely related to the clade-level community structures and abundances of Accumulibacter.