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Anthriscus sylvestris (L.) Hoffm. Gen. is a biennial or perennial herb commonly found in China. It has a long history of use in traditional Chinese medicine to treat various ailments such as cough, gastric disorders, spleen deficiency, and limb weakness. Recently, its potential as an anticancer agent has gained considerable attention and has been the subject of extensive research focusing on extract efficacy, identification of active compounds, and proposed molecular mechanisms. Nevertheless, further high-quality research is still required to fully evaluate its potential as an anticancer drug. This review aims to comprehensively summarize the anticancer properties exhibited by the active components found in Anthriscus sylvestris. We conducted a comprehensive search, collation, and analysis of published articles on anticancer activity and active compounds of A. sylvestris using various databases that include, but are not limited to, PubMed, Web of Science, Science Direct and Google Scholar. The primary chemical composition of A. sylvestris consists of phenylpropanoids, flavonoids, steroids, fatty acids, and organic acids, showcasing an array of pharmacological activities like anticancer, antioxidant, anti-aging, and immunoregulatory properties. Thus, this review highlights the active compounds isolated from A. sylvestris extracts, which provide potential leads for the development of novel anticancer drugs and a better understanding of the plant's pharmacological effects, particularly its anticancer mechanism of action.
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Antineoplásicos Fitogênicos , Neoplasias , Plantas Medicinais , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Plantas Medicinais/química , Neoplasias/tratamento farmacológico , Apiaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Animais , Medicina Tradicional ChinesaRESUMO
Pesticide resistance inflicts significant economic losses on a global scale each year. To address this pressing issue, substantial efforts have been dedicated to unraveling the resistance mechanisms, particularly the newly discovered microbiota-derived pesticide resistance in recent decades. Previous research has predominantly focused on investigating microbiota-derived pesticide resistance from the perspective of the pest host, associated microbes, and their interactions. However, a gap remains in the quantification of the contribution by the pest host and associated microbes to this resistance. In this study, we investigated the toxicity of phoxim by examining one resistant and one sensitive Delia antiqua strain. We also explored the critical role of associated microbiota and host in conferring phoxim resistance. In addition, we used metaproteomics to compare the proteomic profile of the two D. antiqua strains. Lastly, we investigated the activity of detoxification enzymes in D. antiqua larvae and phoxim-degrading gut microbes, and assessed their respective contributions to phoxim resistance in D. antiqua. The results revealed contributions by D. antiqua and its gut bacteria to phoxim resistance. Metaproteomics showed that the two D. antiqua strains expressed different protein profiles. Detoxifying enzymes including Glutathione S-transferases, carboxylesterases, Superoxide Dismutase, Glutathione Peroxidase, and esterase B1 were overexpressed in the resistant strain and dominated in differentially expressed insect proteins. In addition, organophosphorus hydrolases combined with a group of ABC type transporters were overexpressed in the gut microbiota of resistant D. antiqua compared to the sensitive strain. 85.2% variation of the larval mortality resulting from phoxim treatment could be attributed to the combined effects of proteins from both from gut bacteria and D. antiqua, while the individual contribution of proteins from gut bacteria or D. antiqua alone accounted for less than 10% of the variation in larval mortality caused by phoxim. The activity of the overexpressed insect enzymes and the phoxim-degrading activity of gut bacteria in resistant D. antiqua larvae were further confirmed. This work enhances our understanding of microbiota-derived pesticide resistance and illuminates new strategies for controlling pesticide resistance in the context of insect-microbe mutualism.
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Microbioma Gastrointestinal , Praguicidas , Animais , Cebolas , Proteômica , Transportadores de Cassetes de Ligação de ATP , Arildialquilfosfatase , LarvaRESUMO
Insufficient protein intake and cognitive decline are common in older adults; however, there have been few studies on low protein risk screening and complex nutrient interventions for elderly individuals in rural communities. This study aimed to evaluate the effect of dietary multinutrient soy flour (MNSF) on body composition and cognitive function in elderly individuals who are at risk of protein deficiency in a randomized, double-blind, placebo-controlled clinical trial. Nutritional interventions were given to those found to have low protein levels using bioelectrical impedance analysis (BIA). Among 733 older adults screened, 62 participants were included and randomly assigned into two groups, one taking soy flour and the other taking MNSF for 12 weeks. A previous cross-sectional survey found that 35.1% of the elderly people with an average age of 71.61 ± 5.94 years had an inadequate body protein mass proportion. After the intervention, the MNSF group demonstrated a significant improvement in protein mass, muscle mass, mineral levels, skeletal muscle mass, and fat-free mass compared with baseline (all P < 0.05), as well as a better upward trend compared with the soy flour group (P = 0.08; P = 0.07; P = 0.05; P = 0.08; P = 0.07). Regarding the mini-mental state examination (MMSE) scores, the MNSF group showed a significant decrease after 12 weeks (P < 0.05), which were significantly different compared with the soy flour group (P < 0.05). In the future, the application of MNSF as a food-based supplement to improve nutrition and delay cognitive decline in older adults at the risk of protein deficiency may be considered.
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Farinha , Deficiência de Proteína , Humanos , Idoso , Estudos Transversais , Composição Corporal , Suplementos Nutricionais , Cognição , Proteínas de Soja/farmacologia , Dieta com Restrição de Proteínas , Método Duplo-CegoRESUMO
OBJECTIVE: To observe the effect of electroacupunctureï¼EAï¼preconditioning on ferroptosis in rats with cerebral ischemia-reperfusion injury ï¼CIRIï¼, so as to explore the neuroprotective mechanism of EA preconditioning. METHODS: Male SD rats were randomly divided into sham operation, model, EA, inhibitor and inducer groups with 20 rats in each group. The CIRI model was established by modified Zea Longa occlusion of the middle cerebral artery. Before modeling, EA treatment ï¼2 Hz/15 Hz, 1-2 mAï¼ was applied to "Baihui"ï¼GV20ï¼, "Fengfu"ï¼GV16ï¼ and "Dazhui"ï¼GV14ï¼ for rats of the EA group, 20 min a day for 7 consecutive days. Rats of the inhibitor group were intraperitoneally injected with ferristatin-1ï¼25 mg/kgï¼at a slow and uniform rate. Rats of the inducer group were intraperitoneally injected with Erastinï¼100 mg/kgï¼ after 7 days of EA preconditioning, once every 2 h for a total of 4 times. The CIRI models were prepared 2 d later after the above interventions finished by thread-occlusion. The degree of neurological impairment was evaluated by modified Zea Longa score. The percentage of infarct size was calculated by TTC staining. The ultrastructure of neurons in hippocampus was observed by transmission electron microscope. The contents of ferrous ion ï¼Fe2+ï¼, malondialdehyde ï¼MDAï¼ and glutathione ï¼GSHï¼ in cerebral tissue and reactive oxygen species ï¼ROSï¼ in serum were determined by biochemical method. The changes of mitochondrial membrane potential in rats brain tissues were detected by flow cytometry. The mRNA and protein expression levels of glutathione peroxidase 4 ï¼GPX4ï¼, acyl-CoA synthetase long-chain family member 4 ï¼ACSL4ï¼, transferrin receptor ï¼TFRCï¼, 15-lipoxygenase ï¼15-LOXï¼ and cyclooxygenase-2 ï¼COX-2ï¼ in the ischemic hippocampal region of CIRI rats were detected by real-time quantitative PCR and Western blot, respectively. RESULTS: Compared with the sham operation group, the neurological impairment score, the percentage of cerebral infarction area, the contents of MDA and Fe2+ in cerebral tissue as well as ROS in serum, the protein and mRNA expression levels of ACSL4, TFRC, 15-LOX, COX-2 in hippocampal tissue were increased ï¼P<0.01ï¼, while the content of GSH in cerebral tissue, the protein and mRNA expression levels of GPX4 in hippocampal tissue were decreased ï¼P<0.01ï¼, and mitochondria in brain tissue were significantly damaged ï¼P<0.01ï¼ in the model group. Compared with the model group, the above indexes were all reversed ï¼P<0.05, P<0.01ï¼ in the EA group and inhibitor group. Compared with the EA group, the neurological impairment score, the percentage of cerebral infarction area, the contents of MDA and Fe2+ in cerebral tissue as well as ROS in serum, the protein and mRNA expression le-vels of ACSL4, TFRC, 15-LOX, COX-2 in hippocampal tissue were increased ï¼P<0.05, P<0.01ï¼, while the content of GSH in cerebral tissue, the protein and mRNA expression levels of GPX4 in hippocampal tissue were decreased ï¼P<0.01, P<0.05ï¼, and mitochondria in brain tissue were significantly damaged ï¼P<0.05ï¼ in the inducer group. CONCLUSION: EA preconditioning has neuroprotective effect on CIRI rats, which may be related to inhibiting ACSL4/TFRC/15-LOX/COX-2 expression and increasing GSH/GPX4 expression.
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Eletroacupuntura , Ferroptose , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Infarto Cerebral , Ciclo-Oxigenase 2 , Ferroptose/genética , Neurônios , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/terapiaRESUMO
OBJECTIVE: To observe the effect of Tongdu Tiaoshen (promoting the circulation of the governor vessel and regulating the spirit) electroacupuncture (EA) pretreatment on pyroptosis mediated by peroxisome proliferators-activated receptor γ (PPARγ) of the cerebral cortex in rats with cerebral ischemia reperfusion injury (CIRI) and explore the potential mechanism of EA for the prevention and treatment of CIRI. METHODS: A total of 110 clean-grade male SD rats were randomly divided into a sham-operation group, a model group, an EA group, an EA + inhibitor group and an agonist group, 22 rats in each group. In the EA group, before modeling, EA was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14), with disperse-dense wave, 2 Hz/5 Hz in frequency, 1 to 2 mA in intensity, lasting 20 min; once a day, consecutively for 7 days. On the base of the intervention as the EA group, on the day 7, the intraperitoneal injection with the PPARγ inhibitor, GW9662 (10 mg/kg) was delivered in the EA + inhibitor group. In the agonist group, on the day 7, the PPARγ agonist, pioglitazone hydrochloride (10 mg/kg) was injected intraperitoneally. At the end of intervention, except the sham-operation group, the modified thread embolization method was adopted to establish the right CIRI model in the rats of the other groups. Using the score of the modified neurological severity score (mNSS), the neurological defect condition of rats was evaluated. TTC staining was adopted to detect the relative cerebral infarction volume of rat, TUNEL staining was used to detect apoptosis of cerebral cortical nerve cells and the transmission electron microscope was used to observe pyroptosis of cerebral cortical neural cells. The positive expression of PPARγ and nucleotide-binding to oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex was detected with the immunofluorescence staining. The protein expression of PPARγ, NLRP3, cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D (GSDMD) and GSDMD-N terminal (GSDMD-N) in the cerebral cortex was detected with Western blot. Using the quantitative real-time fluorescence-PCR, the mRNA expression of PPARγ, NLRP3, caspase-1 and GSDMD of the cerebral cortex was detected. The contents of interleukin (IL)-1ß and IL-18 in the cerebral cortex of rats were determined by ELISA. RESULTS: Compared with the sham-operation group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.01), pyroptosis was severe, the protein and mRNA expression levels of PPARγ, NLRP3, caspase-1 and GSDMD were elevated (P<0.01); and the protein expression of GSDMD-N and contents of IL-1ß and IL-18 were increased (P<0.01) in the model group. When compared with the model group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1ß and IL-18 were lower (P<0.01) in the EA group and the agonist group; while, in the EA + inhibitor group, the protein expression of PPARγ was increased (P<0.01), the protein and mRNA expression levels of NLRP3 and GSDMD were decreased (P<0.01, P<0.05), the mRNA expression of caspase-1 was reduced (P<0.01); and the contents of IL-1ß and IL-18 were lower (P<0.01). When compared with the EA + inhibitor group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.05, P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1ß and IL-18 were declined (P<0.01) in the EA group. Compared with the agonist group, in the EA group, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.05, P<0.01), the mRNA expression of PPARγ was decreased (P<0.01) and the protein expression of GSDMD-N was elevated (P<0.05); and the contents of IL-1ß and IL-18 were higher (P<0.01). CONCLUSION: Tongdu Tiaoshen EA pretreatment can attenuate the neurological impairment in the rats with CIRI, and the underlying mechanism is related to the up-regulation of PPARγ inducing the inhibition of NLRP3 in the cerebral cortex of rats so that pyroptosis is affected.
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Eletroacupuntura , PPAR gama , Masculino , Animais , Ratos , Ratos Sprague-Dawley , PPAR gama/genética , Piroptose , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Córtex Cerebral , Infarto Cerebral/genética , Infarto Cerebral/terapia , Caspases , RNA MensageiroRESUMO
Pulse lavage (PL) debridement and ultrasound are both known to be the treatment of biofilm-related periprosthetic joint infection (PJI). However, the efficacy of these in combination is unknown in eradicating biofilm from the orthopaedic metal implant surface. This study was conducted to understand the efficacy of PL and ultrasound in combination in eradicating bacterial biofilms on titanium alloy in vitro. Biofilms of Staphylococcus aureus strains were grown on titanium alloy coupons for 24 h. Then, the coupons were taken to each treatment group: (i) debrided with PL, (ii) exposed to ultrasound, or (iii) exposed to both. An untreated biofilm was set as a control group. Viable plate count and confocal microscopy using live/dead staining was used to measure the amount of biofilm. Viable plate count showed an approximate two-log reduction in CFU/cm2 in PL alone, from an initial cell count on the mental surface of approximately 109 CFU/cm2. The ultrasound caused an approximate seven-log reduction, and the combination group eradicated viable biofilm bacteria completely. Confocal imaging corroborated the CFU data. Our results indicate that PL and ultrasound both are remarkably in eradicating biofilm, and the combination of PL and ultrasound is more effective than alone in reducing biofilm.
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Ginsenoside Rg3, a ginsenoside isolated from Panax ginseng, can regulate autophagy via AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. AMPK/mTOR signaling and autophagy have been reported to be involved in osteogenesis. Here, the effect of Rg3 on ovariectomy (OVX)-induced osteoporosis is explored. In vivo, rats were treated with 20 mg/kg Rg3 after OVX and the body weight (BW) was monitored. Bone mineral density (BMD), hematoxylin-eosin staining of femur tissues, osteogenesis, autophagy, and AMPK/mTOR signaling were analyzed. In vitro, MC3T3-E1 cells were treated with 0, 1, 5, 10, 20, and 100 µmol/L Rg3. 10 and 20 µmol/L Rg3, which had no significant effect on cell viability and significantly affected AMPK/mTOR signaling, were chosen for further analysis. Then osteogenic differentiation was induced with Rg3 or/and AMPK inhibitor (Compound C). AMPK/mTOR signaling, autophagy, osteogenic differentiation, and mineralization by Alizarin Red staining were analyzed. The expression or activity of AMPK/mTOR signaling-related proteins, autophagy markers, and osteogenesis markers was measured by western blotting or commercial kits, and cell viability by cell counting kit-8 assay kits. Rg3 significantly alleviated OVX-induced BW increases, BMD declines and histological changes of femur tissues, promoted osteogenesis, autophagy, and AMPK signaling, but inhibited mTOR signaling in vivo. Moreover, Rg3 significantly enhanced AMPK signaling, autophagy, osteogenic differentiation, and mineralization, but suppressed mTOR signaling in vitro. However, Compound C significantly reversed Rg3-induced alterations in vitro, indicating that Rg3 regulated autophagy, osteogenic differentiation, and mineralization via AMPK/mTOR signaling. Hence, it was speculated that Rg3 might attenuate OVX-induced osteoporosis via AMPK/mTOR signaling pathway.
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Proteínas Quinases Ativadas por AMP/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Ginsenosídeos/uso terapêutico , Osteoporose/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Animais , Conservadores da Densidade Óssea/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Ginsenosídeos/farmacologia , Camundongos , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Ovariectomia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Valjatrate E is an iridoid compound extracted from Valeriana jatamansi Jones herb and is the active ingredient in antitumor activity. Here, we reported its action on tumor invasion and metastasis in the human hepatocellular carcinoma HepG2, aiming at a better understanding of the potential mechanism of action of Valjatrate E. HepG2 cells were treated with Valjatrate E at different concentrations. Wound healing assay and transwell chamber assay were used to determine the effects of Valjatrate E on the migration and invasiveness of HepG2 cells, respectively. Moreover, homogeneity and heterotypic adhesion experiments evaluated the adhesion property of HepG2 cells. The molecular mechanisms by which Valjatrate E inhibited the invasion and migration of HepG2 cells were investigated by gelatin zymography experiment and western blot. Treatment with Valjatrate E inhibited the migration and invasion of HepG2 cells. It achieved this by reducing the expression of matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9), by inhibition of heterogeneous adhesion ability, by blocking mitogen-activated protein kinase (MAPK) signaling via inhibiting the phosphorylation of extracellular signal-regulated kinases (p-ERK). Taken together, these findings provide new evidence that mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) signaling pathway plays an important role in promoting invasion and metastasis in HepG2 cells through p-ERK, and MAPK/ERK signaling pathway may be a therapeutic target for tumor.
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MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Iridoides/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Invasividade Neoplásica/patologia , Metástase Neoplásica/tratamento farmacológico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Fosforilação/efeitos dos fármacos , Plantas Medicinais/química , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Valeriana/químicaRESUMO
Oxymatrine (OMT) is a type of alkaloid extracted from a traditional Chinese medicinal herb, Sophora flavescens. Although the antitumor activities of OMT have been observed in various cancers, there are no reports regarding the effects of OMT on human synovial sarcoma. In the present study, we analyzed the antitumor activities of OMT in SW982 human synovial sarcoma cells and determine whether high mobility group box protein 1 (HMGB1)-mediated autophagy was associated with its therapeutic effects. We found that OMT exhibited antitumor activity in SW982 cells and facilitated increases in autophagy. Inhibition of autophagy by 3-MA or ATG7 siRNA increased the level of apoptosis, which indicated that OMT-induced autophagy protected cells from the cytotoxicity of OMT. Administration of OMT to SW982 cells increased the expression of HMGB1. When HMGB1 was inhibited via HMGB1-siRNA, OMT-induced autophagy was decreased, and apoptosis was increased. Furthermore, we found that HMGB1-siRNA significantly increased the expression of p-Akt and p-mTOR. OMT-induced autophagy may be mediated by the Akt/mTOR pathway, and HMGB1 plays a vital role in the regulation of autophagy. Therefore, we believe that combining OMT with an inhibitor of autophagy or HMGB1 may make OMT more effective in the treatment of human synovial sarcoma.
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Alcaloides/farmacologia , Antineoplásicos/farmacologia , Regulação para Baixo , Proteína HMGB1/metabolismo , Quinolizinas/farmacologia , Sarcoma Sinovial/metabolismo , Autofagia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sarcoma Sinovial/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children; some clinical trials have reported the effects of total glucosides of peony (TGP) in the treatment of JIA. However, no systematic review has yet been conducted. In this study, we assessed the efficacy and safety in patients with JIA enrolled in randomized controlled trials (RCTs) of TGP. We extracted data for studies searched from 8 electronic databases that were searched and also evaluated the methodological quality of the included studies. We assessed the following outcome measures: overall response rate, pain, tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness (DMS), grip strength (GS), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse effects (AEs) in short term (4-8 weeks), intermediate term (9-26 weeks), and long term (>26 weeks). The final analysis showed that TGP acted as a unique nonbiologic disease-modifying antirheumatic drug (nonbiologic DMARD), and its therapeutic effects were safe and efficacious for the treatment of JIA with few AEs. However, more high-quality RCTs are needed to confirm these therapeutic effects.
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Salinity is a major stress that adversely affects plant growth and crop production. Understanding the cellular responses and molecular mechanisms by which plants perceive and adopt salinity stress is of fundamental importance. In this work, some of the cellular signaling events including cell death, reactive oxygen species (ROS) generation, and the behaviors of organelles were analyzed in a salt-tolerant species (Keyuan-1) of peppermint (Mentha × piperita L.) under NaCl treatment. Our results showed that 200 mM NaCl treatment elicited a distinct progress of cell death with chromatin condensation and caspase-3-like activation and a dramatic burst of ROS which was required for the execution of cell death. The major ROS accumulation occurred in the mitochondria and chloroplasts, which were the sources of ROS production under NaCl stress. Moreover, mitochondrial activity and photosynthetic capacity also exhibited the obvious decrease in the ROS-dependent manner under 200 mM NaCl stress. Furthermore, the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), and dehydroascorbate reductase (DHAR) as well as the contents of ascorbate and glutathione changed in the concentration-dependent manner under NaCl stress. Altogether, our data showed the execution of programmed cell death (PCD), the ROS dynamics, and the behaviors of organelles especially mitochondria and chloroplasts in the cellular responses of peppermint to NaCl stress which can be used for the tolerance screening, and contributed to the understanding of the cellular responses and molecular mechanisms of peppermint to salinity stress, providing the theoretic basis for the further development and utilization of peppermint in saline areas.
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Mentha piperita/fisiologia , Salinidade , Cloreto de Sódio/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cloroplastos/efeitos dos fármacos , Cloroplastos/metabolismo , Cromatina/metabolismo , Ativação Enzimática/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Malondialdeído/metabolismo , Mentha piperita/citologia , Mentha piperita/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fotossíntese/efeitos dos fármacos , Protoplastos/efeitos dos fármacos , Protoplastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Fatores de TempoRESUMO
Two series of 20 novel 4-aminoquinazoline-urea derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activity against six human cancer cell lines (K562, U937, A549, NCI-H661, HT29 and LoVo) using the MTT-based assay. Most compounds showed significant antiproliferative activities against four solid tumor cell lines, but no or poor activities against two leukemia cell lines. Furthermore, the target compounds were screened for Aurora A/B kinases inhibitory activity. Among them, 7c, 7d, 8c, and 8d are more potent against Aurora A kinase than ZM447439. Docking study of compounds 7d and ZM447439 revealed that they bound strongly to the ATP-binding sites of Aurora A and B. Thus, they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting Aurora kinases.
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Antineoplásicos/química , Aurora Quinase A/antagonistas & inibidores , Aurora Quinase B/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Quinazolinas/química , Ureia/análogos & derivados , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Aurora Quinase A/metabolismo , Aurora Quinase B/metabolismo , Benzamidas/química , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/síntese química , Estrutura Terciária de Proteína , Relação Estrutura-AtividadeRESUMO
Spleen kidney Yang deficiency (SKYD) diarrhea is a common syndrome in tranditional Chinese medicine (TCM). Until now, there is not an ideal SKYD diarrhea rat model for the research. In this study, we compared single factor way (method I, injecting hydrocortisone and gavaging Sennae Folium) with compound factors way(method II, gavaging adenine, improper diet, exhaustion, and gavaging Sennae Folium) on establishing SKYD diarrhea rat model. After modelling, diarrhea index, D-xylose excretory rate, NOS/cGMP signal transduction system, organ index and histopathology examination were used to evaluate the two ways. The results showed that, compared with health group, all the assessment criterias of method I and method II had significant differences (P < 0.01, 0.05). In addition, the index such as diarrhea index, NOS/cGMP signal transduction system, organ index (kidney, testis and thymus) and histopathology examination had significant differences (P < 0.01, 0.05) between method I and method II. In conclusion, the compound factors modelling method better conforms to the symptom of diarrhoea model caused by SKYD. This new modelling method provides a basis for studying on TCM astringents warming and tonifying the spleen and kidney, relieving diarrhea.
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Diarreia/fisiopatologia , Modelos Animais de Doenças , Rim/fisiopatologia , Baço/fisiopatologia , Deficiência da Energia Yang/fisiopatologia , Animais , Diarreia/metabolismo , Diarreia/patologia , Humanos , Rim/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Baço/patologia , Xilose/metabolismo , Deficiência da Energia Yang/metabolismo , Deficiência da Energia Yang/patologiaRESUMO
OBJECTIVE: To investigate the purgative activity difference and mechanism of raw and processed Rhei Radix et Rhizoma. METHODS: Mail mice were divided into 9 groups:normal group (saline), model group, Tongbianling group (1 g/kg), raw Rhei Radix et Rhizoma groups (5.00, 2.50 and 1.25 g/kg), processed Rhei Radix et Rhizoma groups (5.00, 2.50 and 1.25 g/kg). After oral administration for 5 days, the diarrhea experiment and intestinal propelling test were carried out to evaluate the purgative effect difference of raw and processed Rhei Radix et Rhizoma. Wistar rats were divided into normal group (normal saline), model group, Tong-bianling group (0.5 g/kg), raw Rhei Radix et Rhizoma group (1.25 g/kg), processed Rhei Radix et Rhizoma group (1.25 g/kg). The changes of levels of gastin( GAS), motilin( MTL), vasoactive peptide (VIP), neurotensin (NT), somatostatin ( SS), acetylcholinesterase (AchE), substance P(SP) and endothelin (ET-1)in blood of the rats and gastin (GAS), motilin( MTL), vasoactive peptide (VIP) and neurotensin (NT) in colon of the rats were detected. RESULT: The levels of GAS, MTL, VIP, NT, SS, AchE, SP and ET-1 in serum of raw Rhei Radix et Rhizoma group, and GAS, MTL and VIP in colon of raw Rhei Radix et Rhizoma group were different obviously comparing with the processed one (P < 0.01). CONCLUSION: The raw Rhei Radix et Rhizoma and the processed one had obvious differences in regulating intestinal gastrointestinal hormone and neurotransmitter. This effect may be the reason or one of the reasons for purgative activity difference between raw and processed Rhei Radix et Rhizoma.
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Rheum , Animais , Catárticos , Medicamentos de Ervas Chinesas , Masculino , Camundongos , Raízes de Plantas , Ratos , Ratos Wistar , RizomaRESUMO
To explore the responses and feedbacks of the microbes in the sediments of Taihu Lake to the sediment nutrients, an investigation was made on the microbial biomass carbon (MB(C)), microbial biomass nitrogen (MB(N)), microbial biomass phosphorus (MB(P)), and their correlations with the total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP) in the sediments. The microbial biomass in the sediments was 184.66 mg x kg(-1), being higher at the lakeside than in the mid-lake region. The MB(C) was higher in the western coastal region, Zhushan Bay, and Meiliang Bay, with an average of 127.57 mg x kg(-1), MB(N) was higher in Meiliang Bay, Gonghu Bay, mid-lake region close to Meiliang Bay and Gonghu Bay, and eastern costal region, with an average of 19.25 mg x kg(-1), and MB(P) was higher in the eastern region and parts of the mid-lake region, with an average was 19.09 mg x kg(-1). The TOC high value zone (> or = 2.30 g x kg(-1)) was mainly in Zhushan Bay, western coastal region, Meiliang Bay, and Gonghu Bay, with an average of 1.59 g x kg(-1), TN high value zone (> or = 0.30 g x kg(-1)) was mainly in the Gonghu Bay, Meiliang Bay, Zhushan Bay, and western costal region, with an average of 0.21 g x kg(-1), and TP high value zone (> or = 1.20 g x kg(-1)) was mainly in the eastern coastal region and parts of the mid-lake region, with an average of 0.55 g x kg(-1). The TOC/TN ratio in the sediments was 7-19, with an average of 8.97, which showed that the organic substances in the sediments had obvious dual sources, among which, terrestrial organisms were mainly in the west side of the lake. The microbial biomass in the sediments was significantly positively correlated with sediment TOC and TN but had less correlation with sediment TP, and the MB(C)/MB(N) was significantly correlated with sediment TOC/TN, suggesting that the microbes in the sediments of Taihu Lake were mainly affected by the sediment TOC and TN, and the changes of the TOC/TN had significant effects on the microbial community structure.
Assuntos
Carbono/análise , Sedimentos Geológicos/microbiologia , Lagos , Microbiologia da Água , Poluentes Químicos da Água/análise , Biomassa , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Nitrogênio/análise , Compostos Orgânicos/análise , Fósforo/análise , Água/análiseRESUMO
The roots of Polygonum multiflorum (Chinese name: He-Shou-Wu, HSW) are used in traditional Chinese medicine for many diseases in processed form or raw state. There are reports dealing with the toxicity of HSW. However, the toxicity is caused by over dosage or by the herb itself remains unclear. We evaluated the toxicity of raw and processed HSW on Kunming (KM) mice. For raw HSW, the toxicity of water decocta is much higher than that of acetone extract. Meanwhile, the toxicity of acetone extract of raw HSW is considerably higher than that of acetone extract of processed HSW. HPLC analyses revealed that the contents of characteristic compounds in raw HSW were changed after processing: the content of 2,3,4',5-tetrahydroxystilbene 2-O-ß-D-glucoside was decreased by 55.8%, whereas the content of emodin was increased by 34.0%. Thus, processing could reduce the toxicity of HSW. Thus, the toxicity of HSW does not depend on the content of anthranoid derivatives, it may be correlated with the content of tetrahydroxystilbene glucosides.
Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Emodina/toxicidade , Glucosídeos/toxicidade , Raízes de Plantas/toxicidade , Polygonum/toxicidade , Estilbenos/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Emodina/análise , Feminino , Glucosídeos/análise , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Raízes de Plantas/química , Polygonum/química , Estilbenos/análiseRESUMO
A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated surface determinant B (IsdB) of Staphylococcus aureus was isolated from the Cambridge Antibody Technology (CAT) scFv antibody library. As compared to previously described IsdB specific murine monoclonals, CS-D7 has a unique, non-overlapping binding site on IsdB, and exhibits increased in vivo activity. The antibody recognizes a conformational epitope spanning amino acids 50 to 285 and has a binding affinity of 340 (± 75) pM for IsdB. CS-D7 bound to a wide variety of S. aureus strains, but not to an isdB deletion mutant. The antibody mediated opsonophagocytic (OP) killing in vitro and mediated significant protection in vivo. In a murine lethal sepsis model, the antibody conferred protection from death when dosed prior to challenge, but not when dosed after challenge. Importantly, in a central venous catheter (CVC) model in rats, the antibody reduced bacteremia and prevented colonization of indwelling catheters. Protection was observed when rats were dosed with CS-D7 prior to challenge as well as post challenge. IsdB is currently being investigated for clinical efficacy against S. aureus infection, and the activity of this human IsdB specific antibody supplements the growing body of evidence to support targeting this antigen for vaccine development.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Proteínas de Transporte de Cátions/imunologia , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Antibacterianos/metabolismo , Anticorpos Monoclonais/metabolismo , Especificidade de Anticorpos , Bacteriemia/imunologia , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Proteínas de Transporte de Cátions/genética , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Opsonizantes/metabolismo , Fagocitose , Ratos , Ratos Sprague-Dawley , Sepse/microbiologia , Sepse/mortalidade , Sepse/prevenção & controle , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
A Gram-negative, moderately halophilic, short rod-shaped, aerobic bacterium with peritrichous flagellae, strain DQD2-30(T), was isolated from a soil sample contaminated with crude oil from the Daqing oilfield in Heilongjiang Province, north-eastern China. The novel strain was capable of growth at NaCl concentrations of 1-15 % (w/v) [optimum at 5-10 % (w/v)]. Phylogenetic analyses based on 16S rRNA gene sequences showed that the novel strain belonged to the genus Halomonas in the class Gammaproteobacteria; the highest 16S rRNA gene sequence similarities were with Halomonas desiderata DSM 9502(T) (98.8 %), Halomonas campisalis A4(T) (96.6 %) and Halomonas gudaonensis CGMCC 1.6133(T) (95.1 %). The major cellular fatty acids of strain DQD2-30(T) were C(18 : 1)omega7c (43.97 %), C(19 : 0 )cyclo omega8c (23.37 %) and C(16 : 0) (14.83 %). The predominant respiratory lipoquinone was ubiquinone with nine isoprene units (Q9). The DNA G+C content was 67.0 mol%. The DNA-DNA hybridization values of strain DQD2-30(T) with the most closely related species of the genus Halomonas were 51.8 %, 28.4 % and 23.5 % for H. desiderata, H. campisalis and H. gudaonensis, respectively. Based on these analyses, strain DQD2-30(T )(=CGMCC 1.6443(T)=LMG 23896(T)) is proposed to represent the type strain of a novel species, Halomonas daqingensis sp. nov.
Assuntos
Halomonas/classificação , Halomonas/fisiologia , Petróleo , Microbiologia do Solo , Ácidos Graxos/análise , Halomonas/genética , Halomonas/ultraestrutura , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Especificidade da EspécieRESUMO
OBJECTIVE: To investigate the differences of total flavonoid (TF) content and antifree radical activity between the-leaves of bamboo and Gingo biloba, as well as their seasonal changes. METHOD: Spectrophotometery and Chemiluminescence methods were adopted to determine TF and half inhibiting concentration (IC50) on active oxygen free radicals of the leaves of bamboo, phyllostachys nigra (Lodd. ex. Lindl.) Munro, and Ginkgo biloba. Two kinds of leaves were picked in the same plot at the same time monthly. RESULT: The TF of bamboo leaf varied in the range of 0.67%-1.71% (in dry basis of leaf, below as same) throughout a year, the minimum apparing in June and the maximum in July, then going down obviously, and remaining at a much high lever during November to next April. However, the TF of Ginkgo bilabo leaf varied in 1.48%-2.49% during whole growing period, early April to late November. It ascended with the growth of leaf, reaching the top during June and July, the going down slowly, and finally another peak appeared before defoliation. The average IC50 values on O2-. and .OH of bamboo leaf were at 11.0 micrograms.mL-1 and 5.3 mg.mL-1, and Ginkgo biloba at 19.0 micrograms.mL-1 and 3.6 mg.mL-1, respectively. CONCLUSION: The TF content and anti-free radical activity the bamboo leaf are comparable with the leaf of ginkgo biloba, which is a kind of potential resources for natural antioxidant and free radical scavenger.