RESUMO
The elasticities of double-stranded (ds) DNA and RNA, which are critical to their biological functions and applications in materials science, can be significantly modulated by solution conditions such as ions and temperature. However, there is still a lack of a comprehensive understanding of the role of solvents in the elasticities of dsRNA and dsDNA in a comparative way. In this work, we explored the effect of ethanol solvent on the elasticities of dsRNA and dsDNA by magnetic tweezers and all-atom molecular dynamics simulations. We found that the bending persistence lengths and contour lengths of dsRNA and dsDNA decrease monotonically with the increase in ethanol concentration. Furthermore, the addition of ethanol weakens the positive twist-stretch coupling of dsRNA, while promotes the negative twist-stretch coupling of dsDNA. Counter-intuitively, the lower dielectric environment of ethanol causes a significant re-distribution of counterions and enhanced ion neutralization, which overwhelms the enhanced repulsion along dsRNA/dsDNA, ultimately leading to the softening in bending for dsRNA and dsDNA. Moreover, for dsRNA, ethanol causes slight ion-clamping across the major groove, which weakens the major groove-mediated twist-stretch coupling, while for dsDNA, ethanol promotes the stretch-radius correlation due to enhanced ion binding and consequently enhances the helical radius-mediated twist-stretch coupling.
Assuntos
DNA , Etanol , Simulação de Dinâmica Molecular , RNA de Cadeia Dupla , Etanol/química , DNA/química , RNA de Cadeia Dupla/química , Elasticidade , Conformação de Ácido NucleicoRESUMO
Solid dispersion technique is known to be an effective approach for the polymer to keep drugs stable in the solid state, thereby improving the dissolution rate and oral bioavailability through inhibiting reprecipitation in supersaturated solution. In this study, to evaluate the inhibitory effect of polyethylene glycol-6000 (PEG), Polyvinylpyrrolidone K30 (PVP) and Aminoalkyl methacrylate copolymer (Eudragit), the reprecipitation profiles were observed from supersaturated solutions of Patchouli alcohol (PA) in the presence and absence of the polymers. Furthermore, the dissolution profiles of PA solid dispersions formulated with PEG, PVP or Eudragit were compared for investigating the effect on improving dissolution of each polymer. Solid dispersions formulated with Eudragit were found to result in solution with the highest extent of supersaturation. By contrast, PEG and PVP were less effective. At equivalent supersaturation, all three polymers are capable of mitigating reprecipitation relative to that of PA alone. In addition, in the PA solid dispersion with Eudragit (E-SD (1/3)), the highest concentration of supersaturation of PA was maintained for prolonged time. These results unambiguously indicate that it is imperative to select the appropriate polymer and drug/polymer ratio in addition to considering the stability of the supersaturated solution, which was generated following dissolution of amorphous solid dispersion.
Assuntos
Precipitação Química , Química Farmacêutica/métodos , Polímeros/química , Sesquiterpenos/química , Varredura Diferencial de Calorimetria/métodos , Polímeros/metabolismo , Sesquiterpenos/metabolismo , SolubilidadeRESUMO
Near-infrared (NIR) emissive probes are becoming increasingly popular in biological sensing and imaging due to the advantages of non-invasiveness and deep tissue-penetrating ability. Herein, a series of complexes of trivalent lanthanide ions (Ln = Yb, Er, and Gd) with the commercially available azo dye chromophore 2R (Na2H2C2R) as ligand and featuring respectively H2O and dimethylsulfoxide (DMSO) as ancillary ligands have been prepared. Formulated as [Ln2(HC2R)2(H2O)10]·8H2O (1-3, Ln = Yb, Er, Gd) and [Ln2(HC2R)2(DMSO)10]·2DMSO (4-6, Ln = Yb, Er, Gd), their structures have been determined by single-crystal X-ray diffraction studies. Photophysical property studies revealed NIR emissions of the DMSO complexes characteristic of Yb(III) and Er(III), effectively sensitized by the dye ligand arising mainly from the π-π* transition of the chromophore. The long-wavelength excitation of the complexes, covering the whole visible-light range and extending into the NIR region, portends the potential applications of such complexes for flexible bioimaging and sensing.
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Formation of cluster roots is a typical morphological response to phosphorus (P) deficiency in white lupin (Lupinus albus), but its physiological and molecular mechanisms are still unclear. We investigated the role of auxin in the initiation of cluster roots by distinguishing the sources of auxin, measuring the longitudinal distribution patterns of free indole-3-acetic acid (IAA) along the root and the related gene expressions responsible for polar auxin transport (PAT) in different developmental stages of cluster roots. We found that removal of shoot apex or primary root apex and application of auxin-influx or -efflux transport inhibitors, 3-chloro-4-hydroxyphenylacetic acid, N-1-naphthylphthalamic acid and 2,3,5-triiodobenzoic acid, to the stem did not affect the number of cluster roots and the free-IAA concentration in the roots of P-deficient plants, but when these inhibitors were applied directly to the growth media, the cluster-root formation was greatly suppressed, suggesting the fundamental role of root-derived IAA in cluster-root formation. The concentration of free IAA in the roots was higher in P-deficient plants than in P-adequate ones, and the highest in the lateral-root apex and the lowest in the mature cluster roots. Meanwhile the expression patterns of LaAUX1, LaPIN1 and LaPIN3 transcripts related to PAT was consistent with concentrations of free IAA along the lateral root, indicating the contribution of IAA redistribution in the cluster-root development. We proposed that root-derived IAA plays a direct and important role in the P-deficiency-induced formation of cluster roots.
Assuntos
Ácidos Indolacéticos/metabolismo , Lupinus/crescimento & desenvolvimento , Fósforo/deficiência , Raízes de Plantas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas/genética , Ácidos Indolacéticos/farmacologia , Lupinus/efeitos dos fármacos , Lupinus/genética , Ácidos Naftalenoacéticos/farmacologia , Ftalimidas/farmacologia , Raízes de Plantas/efeitos dos fármacosRESUMO
BACKGROUND: Lipid metabolism plays important roles in the whole process of pregnancy. Previous studies have demonstrated abnormalities of lipid metabolism in the placentas of pregnancies obtained by assisted reproductive technology (ART). Therefore, we hypothesized that ART micromanipulation may affect lipid metabolism in offspring, and focused on the fatty acid metabolism in ART male offspring in this study. METHODS: The fatty acid metabolism in the liver, adipose tissue and testis was detected. The comparison between naturally conceived (NC), controlled ovarian hyperstimulation (COH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) mice was made to analyze the effect of ART on offspring. The mice models in this study included two age groups: adult group and old group. The fatty acid composition and the expression of lipid metabolism-related genes were analyzed by GC-MS and qRT-PCR. RESULTS: The fatty acid composition in the liver and adipose tissue were significantly altered in ART mice, but no significant difference was found in the testis. In adipose tissue, ART mice showed decreased monounsaturated fatty acids (MUFAs) and increased polyunsaturated fatty acids (PUFAs) in both adult and old mice, while the alteration of saturated fatty acids (SFAs) in the adult disappeared in the old. In liver, the changes were much complex in adult mice, while increased MUFAs and decreased PUFAs were found in ART old mice. The activities of fatty acid metabolism-related enzymes and the expression of lipogenic and lipolytic proteins changed in ART groups, with the adult mice and old mice showing inconsistent alterations. Further analysis indicated that SFAs was closely associated with the alterations of fatty acid metabolism-related enzyme activities and the expression of lipogenic and lipolytic proteins. Furthermore, we also found that the effect of separated ART treatments on fatty acid metabolism varied with different ages and tissues. CONCLUSIONS: ART treatments had effect on the fatty acid composition in adipose tissue and liver of male mice. The alteration of SFAs content was crucial for the regulation of fatty acid composition. These changes might have potential effects on the health of ART male offspring which need further investigation.
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Tecido Adiposo/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Técnicas de Reprodução Assistida , Testículo/metabolismo , Fatores Etários , Animais , Feminino , Expressão Gênica , Humanos , Masculino , Camundongos , Especificidade de Órgãos , GravidezRESUMO
BACKGROUND: A traditional Chinese Medicine (TCM) formula, HZJW, has been applied in clinics in China for gastrointestinal disorders. However, the therapeutic mechanism underlying its efficacy and safety remained to be defined. The present investigation was undertaken to evaluate the formula HZJW for its gastroprotective potential, possible effect on Helicobacter pylori along with safety to justify its anti-ulcer action and safe clinical application. METHODS: The gastroduodenal cytoprotective potential was evaluated in rodent experimental models (HCl/Ethanol and NSAID-induced ulcer protocols). The anti-H. pylori property was assessed by agar dilution assay in vitro and analysis in vivo including rapid urease test, immunogold test and histopathology. For toxicity assessment, acute toxicity study was performed according to fixed dose procedure with a single oral administration of HZJW to mice. In the oral chronic toxicity, rats (80 males, 80 females) were administrated HZJW orally in 0, 1000, 2500, or 5000 mg/kg/day doses for 26 weeks (n = 40/group of each sex). Clinical signs, mortality, body weights, feed consumption, ophthalmology, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined at the end of the 13- and 26-week dosing period, as well as after the 4-week recovery period. RESULTS: In the HCl/Ethanol-induced ulcer model, it was observed that oral administration with HZJW (260, 520 and 1040 mg/kg) and ranitidine (250 mg/kg) significantly reduced the ulcerative lesion index (116.70 ± 36.4, 102.20 ± 18.20, 84.10 ± 12.1 and 73.70 ± 16.70) in a dose-dependent manner, respectively, with respect to control group (134.10 ± 31.69). Significant inhibition was also observed in ulcerative index from aspirin-induced ulcer model, with decreases of 35.40 ± 5.93, 31.30 ± 8.08, 26.80 ± 8.27and 20.40 ± 6.93 for the groups treated with HZJW and ranitidine, in parallel to controls (41.60 ± 10.80). On the other hand, treatment with HZJW efficaciously eradicated H. pylori in infected mice in rapid urease test (RUT) and immunogold antibody assay, as further confirmed by reduction of H. pylori presence in histopathological analysis. In the in vitro assay, MICs for HZJW and amoxicillin (positive control) were 125 and 0.12 µg/mL respectively. The LD50 of HZJW was over 18.0 g/kg for mice. No drug-induced abnormalities were found as clinical signs, body weight, food consumption, hematology, blood biochemistry, ophthalmology and histopathology results across three doses. No target organ was identified. The No Observed Adverse Effect Level (NOAEL) of HZJW was determined to be 5,000 mg/kg/day for both sexes, a dose that was equivalent to 50 times of human dose. CONCLUSIONS: These results suggested the efficacy and safety of HZJW in healing peptic ulcer and combating H. pylori, which corroborated their conventional indications and contributed to their antiulcer pharmacological validation, lending more credence to its clinical application for the traditional treatment of stomach complaints symptomatic of peptic ulcer disease (PUD). HZJW might have the potential for further development as a safe and effective alternative/complementary to conventional medication in treating gastrointestinal (GI) disorders.
Assuntos
Antibacterianos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Úlcera Péptica/prevenção & controle , Administração Oral , Animais , Antibacterianos/efeitos adversos , Química Farmacêutica , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Esophageal gastric anastomosis is a common surgical technique used to treat patients with gastric cancer who undergo total gastrectomy. However, using simple anastomosis techniques alone may not meet the needs of patients in some cases and can lead to complications such as anastomotic stenosis and ulceration. In order to overcome these issues and improve patient prognosis, muscle flap reconstruction technique has emerged. Muscle flap reconstruction is a method of improving gastric-esophageal anastomosis by transplanting muscle tissue. By covering the anastomotic site with muscle tissue, it not only enhances the stability of the anastomosis site but also increases blood supply, promoting healing and recovery of the anastomosis. Therefore, the use of muscle flap reconstruction technique in esophageal gastric anastomosis during total gastrectomy for gastric cancer is increasingly widely applied. AIM: To determine the effectiveness of esophagogastric anastomosis using the muscle flap reconstruction technology in total abdominal gastrectomy for gastric cancer and perform follow-up experiments to understand the factors affecting patients' prognosis. METHODS: The study subjects were 60 patients with gastric cancer who were admitted to our hospital between October 2018 and January 2022. All patients underwent esophagogastric anastomosis using the double muscle flap reconstruction technology in total abdominal gastrectomy. Perioperative indicators were determined, and patients were followed up for 1 year. Furthermore, patient outcomes were observed within 1 year, followed by patient classification based on different outcomes. Moreover, clinicopathological parameters were observed and relevant factors affecting patient prognosis were analyzed. RESULTS: The operation time was 318 ± 43 min, the formation time of esophageal double muscle flap anastomosis was 110 ± 13 min, the number of lymph node dissections was 26 ± 6, the incision length was 3 ± 0.6 cm, intraoperative bleeding volume was 48 ± 15 mL, first anal exhaust time was 5.3 ± 1.8 d, first meal time was 6.0 ± 1.6 d, length of hospital stay was 11.8 ± 2.5, and treatment cost was 5.8 ± 0.7 thousand yuan. The patient experienced three postoperative complications: 2 cases of pulmonary infection and 1 case of respiratory discomfort. During 1-year follow-up, 50 patients survived and 10 died. Univariate analysis revealed that histological types, tumor size, tumor-node-metastasis staging, vascular invasion, and postoperative adjuvant radiotherapy and chemotherapy were the main factors affecting the prognosis of surviving patients. Furthermore, Cox regression analysis revealed that postoperative adjuvant radiotherapy and chemotherapy were the main factors affecting patient prognosis. The survival time of the survival group was significantly higher than that of the death group (P < 0.05). CONCLUSION: Esophagogastric anastomotic using muscle flap reconstruction exhibits good effects on patients who undergo total abdominal gastrectomy for cancer. Postoperative adjuvant radiotherapy and chemotherapy are the main factors affecting patient prognosis.
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This study focused on the effects of freeze drying (FD) and sprays drying (SD) on the structure and emulsifying properties of yam soluble protein (YSP). The results showed that the surface hydrophobicity (Ho) value, free sulfhydryl group (SH) content, turns content, denaturation temperature and enthalpy value of spray-dried YSP (SD-YSP) were higher than freeze-dried YSP (FD-YSP), but the apparent hydrodynamic diameter (Dh) value of SD-YSP was smaller. The smaller Dh, higher Ho and free SH led to higher percentage of adsorbed proteins and stronger binding between protein and oil droplet in emulsions. Thus, the emulsifying properties of SD-YSP were better, and the SD-YSP-stabilized emulsion had better dynamical rheological properties. Molecular dynamics (MD) simulations suggested that some intramolecular disulfide bonds and hydrogen bonds of dioscorin were broken, and some helices transformed into turns during the SD process. These structural changes resulted in better thermal stability and emulsification properties of SD-YSP.
Assuntos
Dioscorea , Simulação de Dinâmica Molecular , Secagem por Atomização , Liofilização/métodos , Emulsões/químicaRESUMO
Many studies have shown that γ-aminobutyric acid (GABA) exhibits various beneficial biological activities, including gut-modulating, neuro-stimulating, and cardio-protecting activities. Naturally, GABA exists in small amounts in yam, which is primarily synthesized by the decarboxylation of L-glutamic acid in the presence of glutamate decarboxylase. Dioscorin, the major tuber storage protein of yam, has been shown to have good solubility and emulsifying activity. However, how GABA interacts with dioscorin and affects their properties has yet to be clarified. In this research, the physicochemical and emulsifying properties of GABA-fortified dioscorin, which was dried by spray drying and freeze drying, were studied. As results, the freeze-dried (FD) dioscorin produced more stable emulsions, while the spray-dried (SD) dioscorin adsorbed more rapidly to oil/water (O/W) interface. The fluorescence spectroscopy, ultraviolet spectroscopy and circular dichroism spectroscopy showed that GABA changed the structure of dioscorin, by exposing its hydrophobic groups. The addition of GABA significantly promoted the adsorption of dioscorin to the O/W interface and prevented droplets coalescence. The results of molecular dynamics simulation (MD) showed that GABA destroyed the H-bond network between dioscorin and water, increased surface hydrophobicity and finally improved the emulsifying properties of dioscorin.
Assuntos
Simulação de Dinâmica Molecular , Proteínas de Plantas , Proteínas de Plantas/química , Ácido gama-Aminobutírico , Solubilidade , Interações Hidrofóbicas e HidrofílicasRESUMO
Malachite green (MG), a widely-used and recalcitrant dye, has been confirmed to be carcinogenic and mutagenic against many organisms. The main objective of this study is to investigate the capability of Pseudomonas sp. strain DY1 to decolorize MG, and to explore the possible mechanism. The results showed that this strain demonstrated high decolorizing capability (90.3-97.2%) at high concentrations of MG (100-1,000 mg/l) under shaking condition within 24 h. In static conditions, lower but still effective decolorization (78.9-84.3%) was achieved. The optimal pH and temperature for the decolorization was pH 6.6 and 28-30°C, respectively. Mg(2+) and Mn(2+) (1 mM) were observed to significantly enhance the decolorization. The intermediates of the MG degradation under aerobic condition identified by UV-visible, GC-MS and LC-MS analysis included malachite green carbinol, (dimethyl amino-phenyl)-phenyl-methanone, N,N-dimethylaniline, (methyl amino-phenyl)-phenyl-methanone, (amino phenyl)-phenyl methanone and di-benzyl methane. The enzyme analysis indicated that Mn-peroxidase, NADH-DCIP and MG reductase were involved in the biodegradation of MG. Moreover, phytotoxicity of MG and detoxification for MG by the strain were observed. Therefore, this strain could be potentially used for bioremediation of MG.
Assuntos
Corantes/metabolismo , Pseudomonas/metabolismo , Corantes de Rosanilina/metabolismo , Aerobiose , Biodegradação Ambiental , Corantes/toxicidade , Concentração de Íons de Hidrogênio , Medicago sativa/efeitos dos fármacos , Medicago sativa/crescimento & desenvolvimento , Oxirredutases/metabolismo , Peroxidases/metabolismo , Pseudomonas/enzimologia , Corantes de Rosanilina/toxicidadeRESUMO
Asthma is the most common chronic disease of childhood, chronic airway inflammation; bronchial tissue fibrosis, is a pathological feature common to children asthma, and an emerging data has indicted that autophagy plays critical roles in airway inflammation and fibrosis-mediated airway remodeling. The aim of this study was to examine whether the antifibrotic effect of epithelial microRNAs (miRNAs) relies on regulating autophagy-mediated airway remodeling and to identify the factors involved and the underlying mechanisms. Our results showed miR-30a were downregulated in children with asthma and ovalbumin (OVA) mouse model in parallel with the upregulation of autophagy-related proteins; moreover, we observed miR-30a inhibited the autophagy by downregulated autophagy-related 5 (ATG5). Then, we observed that overexpression of miR-30a suppressed the fibrogenesis and autophagic flux which was stimulated by interleukin-33 (IL-33) in bronchial epithelial cells. In vivo experiments showed that miR-30a overexpression decreased airway remodeling by decreased autophagy. This study uncovered a previously unrecognized antifibrotic role of miR-30a in asthma, in IL-33-induced lung epithelial cells in vitro, and in a murine model of OVA-induced airway inflammation in vivo and explored the underlying mechanisms.
Assuntos
Remodelação das Vias Aéreas , Asma/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Autofagia , Células Epiteliais/metabolismo , Pulmão/metabolismo , MicroRNAs/metabolismo , Adolescente , Animais , Asma/genética , Asma/patologia , Asma/fisiopatologia , Proteína 5 Relacionada à Autofagia/genética , Estudos de Casos e Controles , Linhagem Celular , Criança , Modelos Animais de Doenças , Células Epiteliais/patologia , Feminino , Fibrose , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Transdução de SinaisRESUMO
BACKGROUND: Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. PURPOSE: Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. METHODS: The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RESULTS: RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10â¯+â¯OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. CONCLUSION: A Q-marker database of processed RWI by "sweat soaking method" was established according to the results and relationship of "effect-toxicity-chemicals", which provided a scientific evidence for processing methods, mechanism and the clinical application of RWI, also provided experimental results to explore the application of Q-marker in CHM.
Assuntos
Biomarcadores Farmacológicos/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Wikstroemia/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , China/etnologia , Cromatografia Líquida/métodos , Cumarínicos/análise , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/análise , Emodina/análogos & derivados , Emodina/análise , Furanos/análise , Humanos , Lignanas/análise , Espectrometria de Massas/métodos , Camundongos , Extratos Vegetais/análise , Extratos Vegetais/farmacologiaRESUMO
Colorectal cancer (CRC) is a common and lifethreatening type of malignant cancer, which is associated with a high mortality rate. Cisplatin (CDDP) is a commonly used chemotherapy drug with significant side effects. Brusatol (BR) is one of the principal chemical compounds isolated from the Chinese herb Bruceae Fructus, which has been reported to markedly inhibit the proliferation of numerous cancer cell lines. The present study aimed to investigate the possible synergistic anticancer effects of CDDP combined with BR on CT26 cells, and to evaluate the underlying mechanisms of action. The growth inhibitory effects of BR, CDDP, and BR and CDDP cotreatment on CT26 cells were assessed by MTT assay. Cell apoptosis were determined by flow cytometry and western blot analysis. The results indicated that compared with singleagent treatment, cotreatment of CT26 cells with CDDP and BR synergistically inhibited cell proliferation and increased cellular apoptosis. Furthermore, treatment of CT26 cells with CDDP and BR resulted in a marked increase in the release of cytosolic cytochrome c, decreased expression of procaspase3 and procaspase9, and upregulation of the Bcell lymphoma 2 (Bcl2)associated X protein/Bcl2 ratio compared with treatment with BR or CDDP alone. These results strongly suggested that the combination of CDDP and BR was able to produce a synergistic antitumor effect in CRC cells, thus providing a solid foundation for further development of this combination regimen into an effective therapeutic method for CRC.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Neoplasias Colorretais/patologia , Quassinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Citocromos c/metabolismo , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Concentração Inibidora 50 , Camundongos , Quassinas/química , Proteína X Associada a bcl-2/metabolismoRESUMO
Brucein D (BD), a major active quassinoid in Brucea javanica, has exhibited pronounced anticancer activities. However, the biologic mechanisms have not been fully explored. In this study, BD exhibited more potent cytotoxic effect on pancreatic cancer (PanCa) cell lines, while exerted weaker cytotoxic effects on GES-1 cells (non-tumorigenic). BD was shown to elicit apoptosis through inducing both the intrinsic and extrinsic mitochondria-mediated caspase activations. Furthermore, the BD-induced apoptotic effects were dependent on the accumulated reactive oxygen species (ROS) and inactivation of PI3K/Akt signaling pathway. Pretreatment with tempol completely prevented the cellular apoptosis induced by BD, and recovered the inactivation of AKT, which suggested ROS essentially involved in BD-elicited apoptosis and down-regulation of PI3K/Akt pathway. In addition, the results obtained from orthotopic xenograft in nude mice were congruent with those of the in vitro investigations. These results support the notion that BD held good potential to be further developed into an effective pharmaceutical agent for the treatment of PanCa.
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The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of poorly water soluble bioactive constituent patchouli alcohol (PA) that can be used for the preparation of immediate release pellets formulation. Two commercially available grades poloxamer 188 (P 188) and poloxamer 407 (P 407) were selected, and solid dispersions (SDs) containing different weight ratio of PA and poloxamers, and the combination of P 188 and P 407 as dispersing carriers of ternary solid dispersions (tSDs) were prepared by a low temperature melting method and solidified rapidly by dropping into the 10-15 °C condensing agent atoleine. Both PA/P 188 and PA/P 407 binary solid dispersions (bSDs) could remarkably promote the dissolution rate of PA, increasing approximately 16 times in bSDs with poloxamers in comparison with pure PA within 180 min. P188 contributed to a faster dissolution rate than P 407, however, P 407 had a better solubility. It is interesting to note that the incorporation of P 188 in PA/P 407 bSD pellets could strongly enhance the dissolution rate of PA. DSC and FTIR were used to explore the characteristics of PA-SD pellets. The enhancement of dissolution from the SDs may be attributed partly to the reduction in particle size in PA crystalline due to the formation of eutectic system with poloxamers. Moreover, a simple, accurate in-vitro dissolution test method for volatility drug was established, and the process of PA-SD pellets preparation was simple, rapid, cost effective, uncomplicated and potentially scalable.
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This research was intended to investigate the fetal origins of changed birth weight of the offspring born through assisted reproductive technology (ART). The association between hormone and lipid metabolism or body weight has been generally accepted, and as the basic and specific treatment in ART procedure, gonadotropin stimulation might have potential effects on intrauterine lipid metabolism. In our studies, the mice were superovulated with two doses of gonadotropin. The cholesterol metabolism in ovaries and the triglyceride metabolism in embryos were analyzed. The results showed gonadotropin probably accelerated luteinization and induced a longer time follicle development and ovulation, which resulted in histological and morphological alteration of ovary, and increased the cholesterol content and the expressions of steroidogenesis-related genes. In embryos, gonadotropin increased lipid accumulation and decreased fatty acid synthesis in a dose-dependent manner. Moreover, the changes of fatty acid composition were also shown in superovulation groups. Our studies firstly provided the evidence that the superovulation might affect the maternal and fetal lipid metabolism. These variations of lipid metabolism in our results may be associated with birth weight of ART infants.
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Embrião de Mamíferos/metabolismo , Metabolismo dos Lipídeos , Ovário/metabolismo , Superovulação , Animais , Feminino , Expressão Gênica , Gonadotropinas/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Progesterona/sangueRESUMO
Kangtai capsule (KT) is one type of traditional Chinese medicine preparation derived from the proved recipe, which was frequently applied as an effective clinical treatment of IBS. However, there still lack the reasonable and all-round analytical approach and the scientific studies on its underlying mechanisms. Therefore, our study aimed to develop the novel method for evaluating its quality as well as to interpret the potential mechanisms. In our study, high performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of KT. The neonatal maternal separation (NMS) on Sprague-Dawley pups was employed to evaluate the therapeutic effect of KT by virtue of various parameters including visceral hyperalgesia, serum nitric oxide (NO) level, and tissue 5-hydroxytryptamine (5-HT) level. Consequently, a chromatographic condition, which was carried at 30°C with a flow rate of 0.5 ml/min on AQUA 3µ C18 column with mobile phase of acetonitrile and water-phosphoric acid (100:0.1, v/v), was established to give a common fingerprint chromatography under 254 nm with a similarity index of 0.963 within ten batches of KT samples. On the NMS model, KT markedly elevated the pain threshold of NMS rats. Furthermore, KT at three doses significantly decreased 5-HT content from distal colon of visceral hyperalgesia rats induced by NMS, while the significant decrease of 5-HT content in serum was only observed in the group with KT at high dose. However, compared with that in NMS rats without KT, there was no apparent difference of 5-HT level from brain issue in the rats with various doses. Besides, KT could substantially elevate the concentration of NO in the serum. The results showed our study developed the simple, rapid, accurate, reproducible qualitative and quantitative analysis by HPLC fingerprint for the quality control for KT. Data from the pharmacological investigation suggested that the curative effect of KT to the visceral hypersensitivity may be concerned with the level of 5-HT and NO in vivo, promising its potential in irritable bowel syndrome treatment.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Óxido Nítrico/sangue , Serotonina/sangue , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Colo/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/complicações , Privação Materna , Fitoterapia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study the alteration of thymus matrix lymphocyte generator (TSLP) and change of the Th factor in the course of disease development, and to analyze the curative effect of inhalation of Vitamin A (VA) with corticosteroid for the treatment of asthmatic pneumonia. METHODS: Asthmatic pneumonia models were prepared by challenging rats with inhalation of ovalbumin for 4 weeks, and rested for 1 week. The treatment with VA and corticosteroid inhalation for 1 week was followed. The rat thymus and lung specimen were examen by histochemical and immunofluorescence staining. RESULTS: After 4 - 5 weeks of stimulation, there were more TSLP-positive cells and alveolar macrophages (AM) found in thymus and lung tissue of asthmatic group, the cell proliferation in spleen and thymus was obvious, and blood Th factors elevated. The inflammation within the lung tissue aggravated gradually. In VA group, the expression of TSLP and Th2 factors were all lowered at the 4th week. The TSLP expression slightly increased at the 5th week, and the cell proliferation within T-cell zone of spleen and thymus was strong at first and weakened later. Alveolar microphages (AM) increased significantly and the inflammation in the lung subsided gradually at the 5th week. In the hormone group, TSLP and Th2 factors expression in both thymus and lung were decreased at the 5th week, while the cell proliferation in thymus and lung was gradually increased. The quantity of AM was decreased, whereas the inflammation of the lung was increased gradually at the 5th week. CONCLUSION: During asthmatic period elevated TSLP expression was accompanied by Th2 type responses while VA and corticosteroid both suppressed TSLP and Th2 factors expression. VA alone promoted T lymphocyte proliferation as well as the antigen elimination function by AM, after ceasing the usage, the lung inflammation abated gradually. In contrast, after ceasing the use of corticosteroid, inflammation aggravated.