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Exosomes are vesicle-like bodies carrying proteins, RNA, lipids and other bioactive substances, which are secreted from intracellular to extracellular and act on target cells to play their biological functions. Colorectal cancer is one of the malig¬nant tumors with high morbidity and mortality. It has been found that immune cell-derived exosomes participate in the regulation of colorectal cancer growth, invasion, metastasis and other processes. It also plays an obvious role in tumor diagnosis,treat¬ment and post-treatment monitoring. In this review we summa¬rize the research progress of immune cell-derived exosomes in colorectal cancer.
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COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
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Aim To explore the possible mechanism of Tao-Hong-Si-Wu decoction in the treatment of rheumatoid arthritis using network pharmacology. Methods Based on the previous UPLC-Q-TOF-MS
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To observe the effect of total saponins of Clematidis Radix et Rhizoma (TSCR) on serum metabolic profile changes in adjuvant arthritis(AA) rats, and explore its possible action mechanism for AA rats. The AA rat models were induced by Freund's complete adjuvant(FCA), and their histopathological changes were observed. Gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS), principal component analysis(PCA) and partial least squares-discriminant analysis (PLS-DA) were employed to analyze the metabolic profile among normal group, AA model group and TSCR group. Potential biomarkers in the serum were screened based on the variable importance projection(VIP) value>1, P<0.05. As compared with the normal group, 17 potential biomarkers such as aspartic acid, inositol and phenylacetaldehyde were found and identified in the serum of model group rats. As compared with the model group, the above biomarkers were regulated nearly to a normal state after TSCR administration for 16 days. Metabolomic analysis revealed that the total saponins of Clematidis Radix et Rhizoma has a certain therapeutic effect for AA rats, and the mechanism may be related to regulation of lipid metabolism, amino acid metabolism and energy metabolism.
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The experiment's aim was to optimize the processing technology of Xanthii Fructus which through comparing the difference of UPLC fingerprint and contents of toxicity ingredient in water extract of 16 batches of processed sample. The determination condition of UPLC chromatographic and contents of toxicity ingredient were as follows. UPLC chromatographic: ACQUITY BEH C18 column (2.1 mm x 100 mm, 1.7 microm) eluted with the mobile phases of acetonitrile and 0.1% phosphoric acidwater in gradient mode, the flow rate was 0.25 mL x min(-1) and the detection wavelength was set at 327 nm. Contents of toxicity ingredient: Agilent TC-C18 column (4.6 mm x 250 mm, 5 microm), mobile phase was methanol-0.01 mol x L(-1) sodium dihydrogen phosphate (35: 65), flow rate was 1.0 mL x min(-1), and detection wavelength was 203 nm. The chromatographic fingerprints 16 batches of samples were analyzed in using the similarity evaluation system of chromatographic, fingerprint of traditional Chinese medicine, SPSS16.0 and SIMCA13.0 software, respectively. The similarity degrees of the 16 batches samples were more than 0.97, all the samples were classified into four categories, and the PCA showed that the peak area of chlorogenic acid, 3,5-dicaffeoylquinic acid and caffeic acid were significantly effect index in fingerprint of processed Xanthii Fructus sample. The outcome of determination showed that the toxicity ingredient contents of all samples reduced significantly after processing. This method can be used in optimizing the processing technology of Xanthii Fructus.
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Acides caféiques , Toxicité , Chimie pharmaceutique , Chromatographie en phase liquide à haute performance , Méthodes , Médicaments issus de plantes chinoises , Toxicité , Acide quinique , Toxicité , Xanthium , Chimie , ClassificationRésumé
<p><b>OBJECTIVE</b>To understand the status of standard medication of antiretroviral therapy and identify its correlationship with preventing mother-to-child transmission of HIV (PMTCT).</p><p><b>METHODS</b>Qualitative and quantitative methods for measuring of standard medication towards antiretroviral therapy of PMTCT were used in a cross-sectional study of 167 pregnant women who had accessed to PMTCT services and 57 physicians providing service from January 2005 to June 2007 in 5 HIV epidemic counties in Yunnan province.</p><p><b>RESULTS</b>A total of 167 mothers were recruited, of which 65.87% (110/167) demonstrated for standard medication. The percentage of rational selection of antivirus-therapy regimen was 88.02% (147/167). HIV positive mothers with rational using medicine during labor covered 81.37% (131/161). 87.42% (146/167) of women demonstrated good compliance. The main correlations with the standard medication level of HIV positive pregnant women and their infants were as follows: diagnose time (OR = 2.617; 95% CI: 1.184 - 5.783), place of delivery (OR = 0.064; 95% CI: 0.007 - 0.607), minorities (OR = 0.344; 95% CI: 0.162 - 0.730), understanding of HIV women for antiretroviral therapy (OR = 6.843; 95% CI: 1.449 - 32.312), and doctors' cognition about the regimen for antiretroviral therapy was not enough; 5 key knowledge points (purpose of PMTCT, the consequence of not requiring standard medication, the effect of knowing regimens, the relationship of CD4 levels and selected regimens, the side effect of the relevant medicine) score rate was 47.72% (136/285).</p><p><b>CONCLUSION</b>The proportions of standard medication in PMTCT antiretroviral therapy were not high. Standard medication might be associated with multiple factors from doctors, patients and society. It is necessary to make some steps to improve standard medication of antiretroviral therapy in PMTCT.</p>
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Femelle , Humains , Grossesse , Agents antiVIH , Utilisations thérapeutiques , Chine , Études transversales , Infections à VIH , Traitement médicamenteux , Transmission verticale de maladie infectieuse , Complications infectieuses de la grossesse , Traitement médicamenteuxRésumé
Phycocyanin subunits liposomes (PCS-lip) were prepared and its cellular uptake and photodynamic therapy (PDT) effect on cancer cells were studied. In the experiment, film dispersion method was used to prepare phycocyanin subunits liposomes; particle size and distribution were detected by zetasizer and transmission electric microscope; the effects of liposome as carrier on cell uptake in vitro were evaluated in S180 by using fluorescence microscope; and photodynamic therapy effect was assessed with MTT method. As shown in the results, the particle size mainly ranged from 80 nm to 160 nm, and average encapsulation rate was 42.3%. In the concentration of 100 microg x mL(-1), transfection rate reached (18.5 +/- 0.8)% at 2 h, (23.1 +/- 0.9)% at 4 h, keeping a balance in 5-6 h, and its photodynamic therapy effect in vitro improved with the increasing of concentration of phycocyanin subunits liposomes. In the concentration of 200 micro x mL(-1) cell survival rate of BGC-823 and S180 reached (45 +/- 5.2)% and (36 +/- 5.5)%, respectively, and the cell survival rate differentiation between PCS-PDT group and PCS-lip-PDT group reached 7%-11% (P < 0.05). In this study film dispersion method could keep the biological activity of phycocyanin subunits very well. Phycocyanin subunits liposomes will transfect cells more quickly than phycocyanin subunits in the same concentration, and in the same conditions, phycocyanin subunits liposomes have the better PDT effect on cancer cells as they were incubated with cells for 4 h.
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Animaux , Humains , Souris , Lignée cellulaire tumorale , Survie cellulaire , Vecteurs de médicaments , Stabilité de médicament , Liposomes , Chimie , Taille de particule , Photothérapie dynamique , Méthodes , Phycocyanine , Pharmacologie , Sous-unités de protéines , Pharmacologie , Sarcome 180 de Crocker , Anatomopathologie , Tumeurs de l'estomac , AnatomopathologieRésumé
Drug delivery system (DDS) is a novel approach to overcome multidrug resistance (MDR) in tumors nowadays. This work was designed to investigate a new micellar delivery system for in vitro reversal of resistant ovarian tumor cells, based on a nonionic triblock copolymer Pluronic P105 and paclitaxel (PTX). The PTX-loaded polymeric micelles (P105/PTX) were prepared by thin film-hydration methods. Based on the results of single factor experiments, the P105/PTX micelle formulation was optimized by employing the central composite design-response surface methodology. The physico-chemical properties of the P105/PTX micelles were characterized, including micelle size, drug loading coefficient, in vitro release behavior, etc. The cytotoxicity of the P105/PTX micelles was assessed against human ovarian tumor cell line, SKOV-3/PTX, by a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. In order to understand the possible mechanism of Pluronic effects in resistant tumor cells, cellular uptake study of micellar PTX or Rhodamine-123 (R-123) was also carried out. The results showed that the micelle size was about 24 nm with drug loading coefficient of 1.1% and PTX concentration of 700 microg x mL(-1). The cumulative release amount of PTX from the P105/PTX micelles was only 45.4% in 6 h (P < 0.05) and 79.6% in 24 h, whereas Taxol injection in 6 h released 95.2% PTX. The IC50 values of the P105/PTX micelles and Taxol injection against SKOV-3/PTX were 1.14 and 5.11 microg x mL(-1), and resistance reversion index (RRI) was 9.65 and 2.15, respectively. The micellar PTX or R-123 exhibited a significant increase in cellular uptake in resistant SKOV-3/PTX cells compared with free PTX or R-123. These results indicated that PTX could effectively be solubilized by Pluronic P105 block copolymers via thin film-hydration process and formulation optimization, producing nano-scale polymeric micelles with sustained release property in vitro. The P105/PTX micelles were effectively able to reverse resistance to PTX in SKOV-3/PTX tumor cells compared with Taxol injection or free PTX solution, and the enhanced cytotoxicity in the resistant SKOV-3/PTX cell was related to the improved cellular uptake of PTX by Pluronic P105 copolymers.
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Femelle , Humains , Antinéoplasiques d'origine végétale , Chimie , Pharmacologie , Lignée cellulaire tumorale , Vecteurs de médicaments , Systèmes de délivrance de médicaments , Multirésistance aux médicaments , Résistance aux médicaments antinéoplasiques , Excipients , Chimie , Concentration inhibitrice 50 , Micelles , Tumeurs de l'ovaire , Métabolisme , Anatomopathologie , Paclitaxel , Chimie , Métabolisme , Pharmacologie , Taille de particule , Poloxamère , ChimieRésumé
<p><b>OBJECTIVE</b>To evaluate the clinical significance of AFP-L3 in patients with hepatocellular carcinoma.</p><p><b>METHODS</b>Serum AFP-L3 variants were separated by micro centrifugal column, and detected by chemiluminescence.</p><p><b>RESULTS</b>AFP and AFP-L3 levels were higher in patients with hepatocellular carcinoma than those in patients with chronic hepatitis (P<0.001); as a diagnostic target, the sensitivity and specificity of AFP-L3 were 72.3 percent and 97.2 percent, respectively. Eight patients with hepatitis have higher AFP-L3, but none of them were found with carcinoma by CT three months later.</p><p><b>CONCLUSION</b>AFP-L3 is very useful in the diagnosis of patients with hepatocellular carcinoma.</p>
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Carcinome hépatocellulaire , Sang , Diagnostic , Centrifugation , Tumeurs du foie , Sang , Diagnostic , AlphafoetoprotéinesRésumé
<p><b>OBJECTIVE</b>To investigate the apoptosis-inducing effect of endogenous nitric oxide (NO) suppression in gastric cancer cells and its mechanisms.</p><p><b>METHODS</b>Apoptosis of gastric cancer cells was detected by flow cytometry. Expression of phosphorylated FKHRL1 (thr-32, ser-253) and FKHRL1 in gastric cancer cells was analyzed using Western blotting. Immunofluorescence assay was performed to localize the intracellular phosphorylated FKHRL1 (thr-32, ser-253) and FKHRL1. Transfection of FKHRL1-HA wild type and mutant FKHRL1-HA T32A constructs was performed by lipofectamine plus reagent. NO generation was determined by Griess reaction.</p><p><b>RESULTS</b>Gastric cancer cells were significantly apoptotic after treatment with N(G)-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor), compared with the control (P<0.01). The apoptosis of gastric cancer cells induced by L-NMMA was dose-dependent and time-independent. However, the Z-DEVD-fmk, a caspase-3, 6, 7, 8, 10 inhibitor, did not prevent the apoptosis. The immunofluorescence assays showed that FKHRL1 protein was strongly expressed in the nucleu and p-FKHRL1 thr-32 protein was strongly expressed in the cytoplasm of SGC-7901 cells when endogenous nitric oxide generation was blocked by L-NMMA, but no change in FKHRL1 ser-253 phosphorylation. Nevertheless, ROCK protein was strongly expressed in p-FKHRL1 thr-32-positive SGC-7901 cells. The wortmannin, an inhibitor of phosphoinositol-3-OH kinase (PI3K), did not block the phosphorylated FKHRL1 thr-32 protein induced by L-NMMA. However, Y-27632, a specific inhibitor of the protein kinase ROCK, significantly blocked apoptosis induced by phosphorylated FKHRL1 thr-32 (P < 0.01), which was mediated by L-NMMA. A significant decrease in NO generation (P < 0.01) and a significant increase in apoptosis (P < 0.01) were observed when FKHRL1-HA wild-type cells were transfected, which caused increased FKHRL1 thr-32 phosphorylation.</p><p><b>CONCLUSIONS</b>L-NMMA triggers gastric carcinoma cell apoptosis, possibly by promoting FKHRL1 thr-32 phosphorylation and initiating signal of FKHRL1 to ROCK kinase. This apoptotic signaling process is PI3K/Akt as well as caspase-3 independent.</p>
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Humains , Antinéoplasiques , Toxicité , Apoptose , Caspase-3 , Métabolisme , Lignée cellulaire tumorale , Antienzymes , Toxicité , Protéine O3 à motif en tête de fourche , Facteurs de transcription Forkhead , Métabolisme , Protéines et peptides de signalisation intracellulaire , Métabolisme , Monoxyde d'azote , Phosphatidylinositol 3-kinases , Métabolisme , Phosphorylation , Protein-Serine-Threonine Kinases , Métabolisme , Protéines proto-oncogènes c-akt , Métabolisme , Transduction du signal , Tumeurs de l'estomac , Métabolisme , Anatomopathologie , Transfection , oméga-N-Méthylarginine , Toxicité , rho-Associated KinasesRésumé
The effect of initial substrate concentration on the growth,metabolic activities of Photosynthetic bacteria (PSB) in the process of hydrogen production is studied.The empirical relation of the initial substrate concentration to the specific growth rate,specific substrate consumption rate and specific hydrogen production rate of PSB are developed based on the modified Monod model.It is found that the results given by the model are well agreed with the experimental data in growth phase and stationary phase of PSB.Meanwhile,the optimal substrate concentration in the process of growth,metabolism and hydrogen production is 50 mmol/L.Furthermore,when the initial substrate concentration deviates 50 mmol/L,the activation of PSB is limited or inhibited,and the inhibiting effect is more prominent than the limiting effect.In addition,it is demonstrated that initial substrate concentration has little effect on the specific substrate consumption rate.
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The growth characteristics of hydrogen-production photosynthetic bacterial biofilm in a plate-type biofilm bioreactor were studied experimentally.The effect of hydraulic and nutritional conditions on the surface coverage,thickness,dry weight,and density of Rhodoseudomonas palustris biofilm was observed,respectively.Glucose in the influent concentration range from 0.05 to 10 g/L was used as the sole carbon source.Liquid flow rate was varied from 37.8 to 1080ml/h in the experiments.Experimental results showed that the hydraulic and nutritional conditions had significant influences on the growth rate and structure of biofilm.In a lower flow rate range,high liquid flow rate was propitious to the diffusion of substrate from liquid phase to solid-liquid interface,which resulted in the fast development of biofilm on the solid-liquid interface.However,some parts of biofilm were scraped off when the flow rate exceeded a threshold.At a fixed liquid flow rate,the biofilm density increased with the increase in the substrate concentration.The biofilm having thick and loose structure was developed under low substrate concentration condition.The biofilm structure was convenient for the nutrient transfer in the biofilm,which is a survival strategy of microorganisms facing adverse circumstances.
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<p><b>OBJECTIVE</b>To evaluate the clinical characteristics and long-term outcome of 310 cases of thymectomy for myasthenia Gravis.</p><p><b>METHODS</b>The data of 310 patients with thymectomy were analyzed retrospectively to study the patient selection, operative techniques, perioperative management and results for myasthenia Gravis. Absolute and relative scores for clinical evaluation were used as the criteria to determine the therapeutic effects of thymectomy.</p><p><b>RESULTS</b>There were no operative death and postoperative complication rates were 8.7% (27/310). The extra anatomic thymic tissue was found in up to 38.7% (120/310) patients and thymus hyperplasia occurred in 92.9% (288/310) cases. 92.6% (287/310) postoperative patients were followed up for 3 or more months; the percentage of patients being remitted, essentially remitted, significantly effective, effective and non-effective were 7.1% (22/310), 11.3% (35/310) 40.0% (124/310), 27.1% (84/310), 7.1% (22/310) respectively. The total long-term effective rate was 85.5% (265/310). The effective rate for type I, IIa, IIb, III, IV was 90.9% (20/22), 97.6% (40/41), 95.3% (162/170), 80.6% (29/36), 77.8% (14/18) respectively.</p><p><b>CONCLUSIONS</b>Generalized typed and properly selected recurrent ocular-typed patients with Myasthenia Gravis undergoing extensive thymectomy would have good long-term outcomes.</p>