RESUMO
Three polysaccharides, PTC, PTH, and PTB, were extracted from Pinellia ternata using three different extraction conditions: room temperature water, hot water, and 2 % Na2CO3 solution. PTC and PTH were composed of rhamnose, glucose, galactose, mannose, glucuronic acid, galacturonic acid, and arabinose, which combine to form complex structures. PTB was composed solely of glucose and rhamnose. Further analysis indicated that PTC and PTB exhibited triple-helix structures. PTC showed the highest scavenging capacity against DPPH, superoxide anion, and hydroxyl radicals, with half maximal inhibitory concentrations (IC50) of 1004.1, 1584.1, and 1584.1â µg/mL, respectively. Additionally, PTC, PTH, and PTB were subjected to sulfation, phosphorylation, and selenization, resulting in the production of nine derivates. The distinctive absorptive bands of these derivates were determined through infrared spectroscopy. Selenized and sulfated derivates have shown significant antitumor and immunoenhancing properties. Our findings revealed that at 400â µg/mL, the inhibition rate of selenated PTB on HeLa cells was 54.2 % and that on HepG2 cells was 43.1 %. Additionally, selenized PTC displayed significant immunoenhancing activity, with a proliferation rate of 63.7 % at 400â µg/mL in RAW264.7 cells. These results provide valuable evidence supporting the consideration of polysaccharides from Pinellia ternata as a potential candidate for the development of antineoplastic drugs.
Assuntos
Pinellia , Polissacarídeos , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Humanos , Pinellia/química , Células Hep G2 , Células HeLa , Proliferação de Células/efeitos dos fármacos , Camundongos , Animais , Sobrevivência Celular/efeitos dos fármacos , Picratos/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Compostos de Bifenilo/antagonistas & inibidores , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificaçãoRESUMO
BACKGROUND: To investigate the prognostic significance of station 4R lymph node (LN) dissection in patients who underwent operations for right primary non-small cell lung cancer (NSCLC). METHODS: We performed a retrospective study involving patients with right primary NSCLC who received lobotomy or pneumonectomy with mediastinal LN dissection between January 2011 and December 2017. Propensity score matching was performed. Disease-free survival (DFS) and overall survival (OS) were compared between patients with and without station 4R dissection. RESULTS: Our study included 2070 patients, with 207 patients having no station 4R dissection (S4RD- group) and 1863 patients having station 4R dissection (S4RD+ group). The 4R LN metastasis rate was 13.4% (142/1748), higher than that for other mediastinal LN metastases. Compared with the S4RD- group, the S4RD+ group had higher 5-year DFS (48.1% vs. 39.1%, P = 0.009) and OS (54.4% vs. 42.8%, P = 0.025). Station 4R dissection was an independent risk factor for DFS (odds ratio, OR, 1.28, 95% confidence interval, CI, 1.08-1.64, P = 0.007) and OS (OR 1.31, 95% CI 1.04-1.63, P = 0.018). Patients with adjuvant chemotherapy had a better prognosis after station 4R dissection than those without adjuvant chemotherapy (57.4% vs. 52.3%, P = 0.006). The 5-year OS in the station 4R metastasis group was lower than that in the station 4R non-metastasis group (26.9% vs. 44.3%, P = 0.006) among N2 patients. The 5-year OS of the single-station 4R metastasis group was lower than that of the single-station 7 metastasis group (15.7% vs. 51.6%, P = 0.002). CONCLUSIONS: Station 4R metastasis was the highest among all the mediastinal station metastases in right primary NSCLC patients. Station 4R dissection can improve the prognosis and should be recommended as a routine procedure for these patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias do Mediastino , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Excisão de Linfonodo/métodos , Metástase Linfática , Neoplasias do Mediastino/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
Magnolia officinalis Rehd. et Wils. and Magnolia officinalis Rehd. et Wils. var. biloba Rehd. et Wils, as the legal botanical origins of Magnoliae Officinalis Cortex, are almost impossible to distinguish according to their appearance traits with respect to medicinal bark. The application of AFLP molecular markers for differentiating the two origins has not yet been successful. In this study, a combination of e-nose measurements, e-tongue measurements, and chemical analyses coupled with multiple-source data fusion was used to differentiate the two origins. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) were applied to compare the discrimination results. It was shown that the e-nose system presented a good discriminant ability with a low classification error for both LDA and QDA compared with e-tongue measurements and chemical analyses. In addition, the discriminating capacity of LDA for low-level fusion with original data, similar to a combined system, was superior or equal to that acquired individually with the three approaches. For mid-level fusion, the combination of different principals extracted by PCA and variables obtained on the basis of PLS-VIP exhibited an analogous discrimination ability for LDA (classification error 0.0%) and was significantly superior to QDA (classification error 1.67-3.33%). As a result, the combined e-nose, e-tongue, and chemical analysis approach proved to be a powerful tool for differentiating the two origins of Magnoliae Officinalis Cortex.
Assuntos
Magnolia , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Cromatografia Gasosa , Nariz Eletrônico , Magnolia/química , LínguaRESUMO
A pilot-scale multistage constructed wetland-pond (MCWP) system with a "pre-ecological oxidation pond, two-stage horizontal subsurface flow constructed wetland (HSCW) and surface flow constructed wetland (SFCW) as the core and postsubmerged plant pond" as the process was used to treat actual polluted river water in the field, and the variation in nitrogen removal from summer to winter was investigated. The results showed that the average total nitrogen (TN) removal efficiency in the MCWP was approximately 40.74%. The significant positive correlation between the daily highest temperature and the TN removal efficiency of the whole system was fitted with a nonlinear curve (R2 = 0.7192). The TN removal load rate in the HSCWs was 2.7-3.7 times that in the SFCW. The SFCW, which had high-density plants (35 plants/m2), increased the proportion of nitrogen removed by plant harvesting and microbial function. The TN transformed by Iris pseudacorus L. accounted for 54.53% in the SFCW. Furthermore, bacteria completed the nitrogen cycle in the SFCW through a variety of nitrogen removal pathways. This research not only investigated the TN removal performance in an MCWP system but also made it possible to predict the TN removal efficiency according to the daily highest temperature from summer to winter in the field.
Assuntos
Nitrogênio , Áreas Alagadas , Desnitrificação , Estações do Ano , Eliminação de Resíduos LíquidosRESUMO
Antibiotics are widely detected in the water environment, posing a serious threat to the health of humans and animals. The effect of levofloxacin (LOFL) on pollutant removal and the difference in the influence mechanisms at normal and low temperatures in constructed wetlands are worth discussing. A hydroponic culture experiment was designed with Iris pseudacorus L. at low and normal temperatures. LOFL (0-100 µg/L) was added to the systems. The results indicated that the removal of pollutants was affected most by temperature, followed by LOFL concentration. At the same concentration of LOFL, the pollutant removal rate was significantly higher at normal temperature than at low temperature. Low concentrations of LOFL promoted the degradation of pollutants except TN under normal-temperature conditions. Compared with the results at low temperature, the bacterial community richness was higher and the diversity of bacterial communities was lower under normal-temperature conditions. The genera and the function of bacteria were greatly affected by antibiotic concentration, temperature and test time. A series of microorganisms resistant to antibiotics and low temperature were identified in this study. The results will provide valuable information and a reference for our understanding of the ecological effects of LOFL.
Assuntos
Hidroponia , Gênero Iris/microbiologia , Eliminação de Resíduos Líquidos/métodos , Antibacterianos/metabolismo , Bactérias , Humanos , Iris , Gênero Iris/metabolismo , Temperatura , Águas Residuárias/química , Águas Residuárias/microbiologia , Áreas AlagadasRESUMO
On the basis of the qualitative preparation quality markers of Yulian Decoction, we screened out the quantitative markers and explored a general strategy for analyzing the component migration in Chinese herbal pieces, preparations, and plasma. A method capable of simultaneously determining 28 chemical components in Yulian Decoction was established based on HPLC-MS/MS. This method was used to determine the migrated components in herbal pieces-lyophilized powder preparations-rat plasma after administration of Yulian Decoction. Liquid chromatography was performed under the following conditions: C_(18)-reversed phase chromatographic column(2.1 mm × 100 mm, 1.8 µm); acetonitrile-water(containing 0.1% formic acid) as the mobile phase for gradient elution; the flow rate of 0.2 mL·min~(-1). Electrospray ionization source was adopted for mass spectrometry detection, in which positive and negative ion modes and multiple reaction monitoring were applied. Confirmed by the methodological investigation in linear range, recovery(95.48%-103.4%), precision(RSD, 0.45%-3.8%), stability, and repeatability(RSD, 5.6%-14%), the established method was suitable for the detection and quantification of the components in Yulian Decoction. The results showed that in the lyophilized powder of Yulian Decoction, berberine was greater than 5% in mass fraction, magnoflorine, epiberberine, coptisine, palmatine, and limonin in the range of 1%-5%, and dehydroevodiamine, evodiamine, rutaecarpine, costunolide, and dehydrocostus lactone in the range of 0.002%-1%. Of the 28 components detected in pieces, 27 were found to migrate to the lyophilized powder, and 11 were detected in rat plasma. Fifteen components were preliminarily determined as quantitative preparation quality markers for Yulian Decoction, including berberine, epiberberine, coptisine, palmatine, evodiamine, rutaecarpine, limonin, costunolide, dehydrocostus lactone, magnoflorine, jatrorrhizine, columbamine, groenlandicine, chlorogenic acid, and neochlorogenic acid. In conclusion, the HPLC-MS/MS general strategy was established for analyzing the migration of multiple components in Chinese herbal pieces, preparations, and plasma, which can provide the basis for the screening of quantitative preparation quality markers and multi-index quality control of Yulian Decoction.
Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ratos , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1ß(IL-1ß), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.
Assuntos
Neuralgia , Receptores de N-Metil-D-Aspartato , Animais , Sensibilização do Sistema Nervoso Central , Neuralgia/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Medula Espinal/metabolismoRESUMO
The case-control study was designed to investigate the genetic effects of interferon-gamma (IFN-γ) rs2069727 and rs1861494 polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Blood samples were collected from 108 AS patients and 110 healthy controls. IFN-γ polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Hardy-Weinberg equilibrium (HWE) test was performed in control group. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using chi-square test to evaluate the association between AS susceptibility and IFN-γ polymorphisms, and the results were adjusted by logistic regressive analysis. The frequency of rs2069727 CC genotype was much higher in cases than that in controls, suggested its significant association with increased AS risk (adjusted OR = 5.899, 95% CI = 1.563-22.261; P = .009). In addition, C allele also showed close association with increased risk of AS (adjusted OR = 2.052, 95% CI = 1.286-1.704, Pâ = 0â.003). While the genotype and allele frequencies of IFN-γ rs1861494 polymorphism were not significantly different between patients and controls (Pâ > 0.05 for all), IFN-γ rs2069727 polymorphism is significantly associated with increased AS risk in a Chinese Han Population.
Assuntos
Interferon gama/genética , Polimorfismo de Nucleotídeo Único , Espondilite Anquilosante/genética , Alelos , Animais , Estudos de Casos e Controles , China/epidemiologia , Etnicidade/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Fragmento de Restrição , Ratos , Risco , Espondilite Anquilosante/etnologiaRESUMO
Transition metal phosphides (TMPs) are certified high performance electrocatalysts for the hydrogen evolution reaction (HER). The ultrathin 2D structure of TMPs can offer abundant adsorption sites to boost HER performance. Herein, an ice-templating strategy is developed to prepare CoP aerogels composed of 2D ultrathin CoP nanosheets (<1.5 nm) using sustainable alginate biomass (seaweed extract) as the precursor. The highly porous aerogel structure can not only deliver facile mass transfer, but also prevent aggregation of the nanosheets into layered structures. As expected, the obtained CoP nanosheet aerogels exhibit remarkable stability and excellent electrocatalytic HER performance at all pH values. For instance, the sample CoP-400 presents a low overpotential of 113, 154, and 161 mV versus RHE at a current density of 10 mA cm-2 in 0.5 m H2SO4, 1 m KOH, and 1 m phosphate buffer solution, respectively. In addition, CoP-400 displays low Tafel slopes at all pH values due to the interconnected highly porous structure of the aerogel, indicating that the sample can provide low-resistance channels for mass transport. Density functional theory calculations reveal that P-top and Co bridge on (011) facet of CoP are more favorable sites during the process of HER in acid and alkaline solutions, respectively.
RESUMO
Heavy metals in the environment are one of the major limiting factors affecting plant growth and development. However, the mechanisms of the heavy metal-induced physiological processes remain to be fully dissected. Here, we explored that SRO1 can physically interact with Glutathione Peroxidase 3 (GPX3) in Arabidopsis. Under Hg treatment, similar to the sro1, the growth of the gpx3/sro1 was repressed more seriously and the number of true leaves was more reduced and etiolated than that of the wild type and gpx3 plants. The electrolyte leakage rates showed that cell membrane integrity in gpx3/sro1 was damaged more severely than in the wild type and gpx3 mutant. The Real-time PCR results have shown that the expression of the APX1 and CAT3 was reduced under mercury stress in the sro1 and sro1/gpx3. Our results suggested that the combination of the SRO1 and GPX3 may be contributed to plant response to mercury stress by regulating ROS intracellular oxidative homeostasis.
Assuntos
Proteínas de Arabidopsis/química , Arabidopsis , Glutationa Peroxidase/química , Mercúrio/toxicidade , Proteínas Nucleares/química , Estresse Fisiológico , Proteínas de Arabidopsis/metabolismo , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Homeostase , Proteínas Nucleares/metabolismo , Estresse Oxidativo , Reação em Cadeia da PolimeraseRESUMO
As an important glycosaminoglycan, keratan sulfate (KS) mainly exists in corneal and cartilage, possessing various biological activities. In this study, we purified KS from blue shark (Prionace glauca) cartilage and prepared KS oligosaccharides (KSO) through keratanase II-catalyzed hydrolysis. The structures of KS and KSO were characterized using multi-dimensional nuclear magnetic resonance (NMR) spectra and liquid chromatography-mass spectrometry (LC-MS). Shark cartilage KS was highly sulfated and modified with ~2.69% N-acetylneuraminic acid (NeuAc) through α(2,3)-linked to galactose. Additionally, KS exhibited binding affinity to Ricinus communis agglutinin I (RCA120) in a concentration-dependent manner, a highly toxic lectin from beans of the castor plant. Furthermore, KSO from dp2 to dp8 bound to RCA120 in the increasing trend while the binding affinity of dp8 was superior to polysaccharide. These results define novel structural features for KS from Prionace glauca cartilage and demonstrate the potential application on ricin-antidote exploitation.
Assuntos
Cartilagem/química , Sulfato de Queratano/química , Lectinas de Plantas/química , Tubarões/metabolismo , Acetilglucosaminidase/química , Animais , Cromatografia Líquida , Galactose/química , Hidrólise/efeitos dos fármacos , Espectroscopia de Ressonância Magnética/métodos , Oligossacarídeos/química , Espectrometria de Massas em Tandem/métodosRESUMO
As shown in our previous study, sinomenine hydrochloride (SH), the major bioactive alkaloid isolated from Sinomenium acutum Rehd. et Wils. (Fam. Menispermaceae), initiates the autophagy-mediated death of human glioblastoma cells by generating reactive oxygen species and activating the autophagy-lysosome pathway. However, its effects on the migration and invasion of human glioblastoma cells have not yet been elucidated. Therefore, human glioblastoma U87 and SF767 cells were treated with SH (0.125 and 0.25 mM) for 24 h, and cell migration and invasion were assessed using scratch wound healing, migration and invasion assays. SH promoted G0/G1 phase arrest, inhibited the migration and invasion of the two cell lines, suppressed the activation of nuclear factor kappa B (NFκB) and the expression of matrix metalloproteinase (MMP)-2/-9, triggered endoplasmic reticulum (ER) stress, reversed the exogenous epithelial-mesenchymal transition (EMT) induced by the inflammatory microenvironment and the endogenous EMT. Additionally, NFκB p65 overexpression blocked the SH-mediated inhibitory effects on MMP-2/-9 expression and cell invasion. SH-induced autophagy was reduced in CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) or autophagy-related 5 (ATG5)-silenced human glioblastoma cells and cells treated with 4-phenylbutyric acid (4-PBA) or 3-methyladenine (3-MA), as shown by the decreased levels of the microtubule-associated protein light chain 3B (LC3B)-II and autophagic vacuoles (AVs) stained with monodansylcadaverine (MDC), respectively. Moreover, knockdown of CHOP or ATG5 and treatment with 4-PBA or 3-MA abolished the SH-mediated inhibition of mesenchymal markers (vimentin, Snail and Slug) expression and cell invasion, respectively. Importantly, SH also regulated the above related pathways in nude mice. Based on these findings, SH inhibited cell proliferation by inducing cell cycle arrest, and attenuated the metastasis of U87 and SF767 cells by suppressing MMP-2/-9 expression and reversing the endogenous and exogenous EMT in vitro and/or in vivo. Thus, SH might be a new potential anti-metastasis agent for the treatment of human glioblastoma.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/metabolismo , Transição Epitelial-Mesenquimal , Glioblastoma/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Morfinanos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genéticaRESUMO
Chemically durable and effective absorbent materials for selenite (SeO32- ) remain highly desirable for contamination remediation. Now a bismuth-based metal-organic framework (Bi-MOF, CAU-17) was used as adsorbent to capture SeO32- anions from aqueous solution with ultrahigh adsorption capacity of 255.3â mg g-1 and fast kinetics. Furthermore, the adsorbent showed excellent selectivity for SeO32- and was able to work steadily in a broad pH range of 4-11. Density functional theory (DFT) calculation, XANES modeling, and EXAFS fitting suggested that SeO32- anions were immobilized by forming Bi-O-Se bonds (T-3 structural model) though splitting the O-Bi-O bond in the crystal structure, leading to a structural transformation of CAU-17 in the solid state.
RESUMO
Glioblastoma is the most common malignant primary brain tumor, and it is one of the causes of cancer fatality in both adult and pediatric populations. Patients with glioblastoma require chemotherapy after surgical resection and radiotherapy. Therefore, chemotherapy constitutes a viable approach for the eradication of glioblastoma cells. In this study, the anti-tumor activity of sinomenine hydrochloride (SH) was evaluated in U87 and SF767 cells in vitro and in vivo. The results showed that SH potently inhibited U87 and SF767 cell viability and did not cause caspase-dependent cell death, as demonstrated by the absence of significant early apoptosis and caspase-3 cleavage. Instead, SH activated an autophagy-mediated cell death pathway, as indicated by the accumulated microtubule-associated protein light chain 3B (LC3B)-II, triggered autophagic flux and enhanced cell viability after pretreatment with autophagy inhibitors. SH-mediated autophagy in the two cell lines was implicated in reactive oxygen species (ROS) generation, protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway suppression and c-Jun NH2-terminal kinase (JNK) pathway activation. The ROS antioxidant N-acetylcysteine (NAC), the Akt-specific activator insulin-like growth factor-1 (IGF-1) and the JNK-specific inhibitor SP600125 attenuated SH-induced autophagy. Moreover, ROS activated autophagy via the Akt-mTOR and JNK pathways. Additionally, SH treatment may promote lysosome biogenesis through activating transcription factor EB (TFEB). The in vivo study found that SH effectively suppressed glioblastoma growth without exhibiting significant toxicity. In conclusion, our findings reveal a novel mechanism of action of SH in cancer cells via the induction of autophagy through ROS generation and autophagy-lysosome pathway activation; these findings also supply a new potential therapeutic agent for the treatment of human glioblastoma.
Assuntos
Antineoplásicos/uso terapêutico , Autofagia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Lisossomos/efeitos dos fármacos , Morfinanos/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Glioblastoma/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/metabolismo , Morfinanos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mgâ¢kg⻹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mgâ¢kg⻹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mgâ¢kg⻹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(P<0.01, P<0.05), decrease the level of Glu(P<0.01, P<0.05), improve the levels of GABA, Gly, Tau(P<0.01, P<0.05), lower the ratio of Glu/GABA(P<0.01, P<0.05), and reduce the levels of RANTES, MCP-3(P<0.05) in the L3-L5 spinal cord, and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points(P<0.05).This study showed that CQ prescription had significant analgesic effect on CIIMIP model mice, and its mechanism was associated with regulating the balance between excitability amino acid(EAA) and inhibitory amino acid (IAA) transmitters in central nervous system, partially activating GABAa receptor, and reducing the release of RANTES and MCP-3 in the spinal cord.
Assuntos
Analgésicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Experimentais/complicações , Dor/tratamento farmacológico , Animais , Ácido Glutâmico/análise , Glicina/análise , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Medula Espinal/química , Taurina/análise , Ácido gama-Aminobutírico/análiseRESUMO
The low-molecular-weight fucosylated chondroitin sulfate (LFCS) was prepared from native fucosylated chondroitin sulfate (FCS), which was extracted and isolated from sea cucumber Cucumaria frondosa, and the anti-cancer mechanism of LFCS on mouse Lewis lung carcinoma (LLC) was investigated. The results showed that LFCS remarkably inhibited LLC growth and metastasis in a dose-dependent manner. LFCS induced cell cycle arrest by increasing p53/p21 expression and apoptosis through activation of caspase-3 activity in LLC cells. Meanwhile, LFCS suppressed the expression of vascular endothelial growth factor (VEGF), increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and downregulated the matrix metalloproteinases (MMPs) level. Furthermore, LFCS significantly suppressed the activation of ERK1/2/p38 MAPK/NF-κB pathway, which played a prime role in expression of MMPs. All of these data indicate LFCS may be used as anti-cancer drug candidates and deserve further study.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Sulfatos de Condroitina/administração & dosagem , Pepinos-do-Mar/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sulfatos de Condroitina/química , Sulfatos de Condroitina/isolamento & purificação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Peso Molecular , Metástase Neoplásica , Proteínas de Neoplasias/biossíntese , Transdução de Sinais/efeitos dos fármacosRESUMO
We analyze the design of near infrared all-optical controllable and dynamically tunable multispectral Fano resonances based on subgroup decomposition of plasmonic resonances in hybrid nanoslits antenna plasmonic system. The theoretical investigation complemented with numerical simulations show that the Fano resonance lines shape can be tailored efficiently and continuously with the nanoslits geometry and the variation of the polarization states of the incident light. The subgroup decomposition of the spectral profile and the modification of plasmonic resonances lineshape that leads to the Fano-type profile of transmission is investigated and revealed. The separate contribution from individual spectral of single-slit array subgroup is attributed to the resulting overall multispectral Fano lineshape of the proposed T-shaped slits array at their corresponding spectral peaks zone. The polarization-selective tunability of the multispectral Fano resonances in the planar hybrid plasmonic system creates new avenues for designing multi-channel multi-wavelength tunable Fano effect.
RESUMO
This study aims to investigate the expression level of pro-opiomelanocortin (POMC) and its prognostic value in non-small cell lung cancer (NSCLC). Immunohistochemical staining was used to detect the expression level of POMC. Correlations between POMC expression and clinical and pathological characteristics were evaluated with the chi-square test, and the prognostic value was determined with the Kaplan-Meier method and COX proportional hazards model, α < 0.05. Of the samples, 48.0% had positive POMC expression. POMC expression was significantly related to poorly differentiated tumors, N-stage, p-stage, postoperative failure pattern, expression of vimentin, and expression of E-cadherin (P < 0.05). Multivariate analysis revealed that POMC-positive expression was an independent risk factor for disease-free survival (hazard ratio (HR) 1.988, 95% confidence interval (CI) 1.094-3.910, P = 0.024) and overall survival (HR 1.892, 95% CI 1.726-3.709, P = 0.036). The addition of POMC protein expression to the prognostic model using pathological stage markedly improved the prognostic potential, and the area under the ROC increased from 0.691 to 0.775. Further study revealed that patients with POMC-negative expression can benefit more from a regimen of paclitaxel and carboplatin chemotherapy than a regimen of vinorelbine and carboplatin compared to patients with POMC-positive expression. We found that POMC-positive expression is a novel, independent poor prognostic marker in patients with NSCLC. Prospective studies are needed to validate the potential prognostic value of POMC in combination with the current staging system and in consideration of adjuvant chemotherapy.
Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Pró-Opiomelanocortina/biossíntese , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Caderinas/biossíntese , Caderinas/genética , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Pró-Opiomelanocortina/genética , Prognóstico , Vimentina/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
An apigalacturonan (AGA)-rich polysaccharide, ZCMP, was isolated from the sea grass Zostera caespitosa Miki. The depolymerized fragments derived from ZCMP were obtained by either acidic degradation or pectinase degradation, and their structures were characterized by electrospray ionization collision-induced-dissociation mass spectrometry (ESI-CID-MS2) and nuclear magnetic resonance (NMR) spectroscopy. The average molecular weight of ZCMP was 77.2 kD and it consisted of galacturonic acid (GalA), apiosefuranose (Api), galactose (Gal), rhamnose (Rha), arabinose (Ara), xylose (Xyl), and mannose (Man), at a molar ratio of 51.4ê15.5ê6.0ê11.8ê4.2ê4.4ê4.2. There were two regions of AGA (70%) and rhamnogalacturonan-I (RG-Ι, 30%) in ZCMP. AGA was composed of an α-1,4-D-galactopyranosyluronan backbone mainly substituted at the O-3 position by single Api residues. RG-Ι possessed a backbone of repeating disaccharide units of â4GalAα1,2Rhaα1â, with a few α-L-arabinose and ß-D-galactose residues as side chains. The anti-angiogenesis assay showed that ZCMP inhibited the migratory activity of human umbilical vein endothelial cell (HUVECs), with no influence on endothelial cells growth. ZCMP also promoted macrophage phagocytosis. These findings of the present study demonstrated the potential anti-tumor activity of ZCMP through anti-angiogenic and immunoregulatory pathways.
Assuntos
Inibidores da Angiogênese/farmacologia , Polissacarídeos/farmacologia , Zosteraceae/química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Fagocitose/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Astrocyte-like glial cells are abundant in the central nervous system of adult Drosophila and exhibit morphology similar to astrocytes of mammals. Previous evidence has shown that astrocyte-like glial cells are strongly associated with synapses in the antennal lobe (AL), the first relay of the olfactory system, where olfactory receptor neurons (ORNs) transmit information into projection neurons (PNs). However, the function of astrocyte-like glia in the AL remains obscure. In this study, using in vivo calcium imaging, we found that astrocyte-like glial cells exhibited spontaneous microdomain calcium elevations. Using simultaneous manipulation of glial activity and monitoring of neuronal function, we found that the astrocyte-like glial activation, but not ensheathing glial activation, could inhibit odor-evoked responses of PNs. Ensheathing glial cells are another subtype of glia, and are of functional importance in the AL. Electrophysiological experiments indicated that astrocyte-like glial activation decreased the amplitude and slope of excitatory postsynaptic potentials evoked through electrical stimulation of the antennal nerve. These results suggest that astrocyte-like glial cells may regulate olfactory processing through negative regulation of ORN-PN synaptic strength. Beyond the antennal lobe we observed astrocyte-like glial spontaneous calcium activities in the ventromedial protocerebrum, indicating that astrocyte-like glial spontaneous calcium elevations might be general in the adult fly brain. Overall, our study demonstrates a new function for astrocyte-like glial cells in the physiological modulation of olfactory information transmission, possibly through regulating ORN-PN synapse strength.