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1.
Acta Pharmaceutica Sinica ; (12): 3224-3232, 2021.
Article in Chinese | WPRIM | ID: wpr-906849

ABSTRACT

In this study, exosomes were extracted from human malignant melanoma cell A375. Folic acid (FA) receptor was used as target and triptolide (TPL) was used as model drug to prepare exosome targeted drug delivery system, FA-Exo/TPL. The physicochemical properties and antitumor effect were evaluated in vivo and in vitro. Gradient centrifugation method was applied to collect exosomes. Then, exosome was modified with FA for loading TPL. The particle sizes of the FA-Exo/TPL were about 100 nm with a double-layer membrane structure like a tray. It is characteristic of high encapsulation efficiency and drug loading. In vitro experiments showed that FA-Exo/TPL could be effectively uptaken by A375 cells, thus significantly inhibiting proliferation and promoting apoptosis the cells. In vivo experiment results showed that FA-Exo/TPL could effectively inhibit the growth of tumor tissue, prolong the model mice life cycle, and significantly reduce the systemic toxicity of the free drug, playing a synergistic and toxic role. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Fudan University Shanghai Cancer Center. This study provides a new strategies and methods for the preparation of TPL against malignant melanoma.

2.
Article in Chinese | WPRIM | ID: wpr-921772

ABSTRACT

When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.


Subject(s)
Astrocytes , Axons/pathology , Cicatrix/pathology , Gliosis/pathology , Humans , Medicine, Chinese Traditional , Nerve Regeneration , Stroke/drug therapy
3.
Journal of Medical Postgraduates ; (12): 422-427, 2020.
Article in Chinese | WPRIM | ID: wpr-821867

ABSTRACT

Malignancy is one of the leading causes of death worldwide. Effective screening and early diagnosis of tumors are clinically difficult. The existing tumor markers have low sensitivity and poor specificity. Exosomes, the nanoscale vesicles with a phospholipid bilayer structure, are widely distributed in various body fluids. Studies have shown that tumor-derived exosomes (TEXs) are closely related to the occurrence and progression of cancers. The contents of TEXs including proteins, RNA and DNA, glycoproteins, glycolipids and lipids can serve as highly sensitive tumor-specific markers, playing a crucial role in the basic research and clinical examination of cancers. Therefore, TEXs are expected to become new non-invasive tumor diagnostic biomarkers. This review describes the biological characteristics of exosomes, their advantages as diagnostic biomarkers and their applications in diagnosis of tumors, treatment monitoring and prognosis evaluation.

4.
Article in Chinese | WPRIM | ID: wpr-305346

ABSTRACT

The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels and investigate its pharmacodynamics. Oleic acid was used as oil phase, polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the model of mouse chronic dermatitis and eczema. The concentrations of IFN-γ, IL-4 and IL-8 in mouse blood were determined by ELISA. The results showed that Tripterygium glycosides nanoemulsion gels could significantly inhibit the swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model mouse ears skin. Also it could significantly decrease the expression of IFN-γ and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a good therapeutic effect on mouse model of dermatitis and eczema. It was expected to provide a new and long-acting exterernal preparation for the treatment of dermatitis and eczema.


Subject(s)
Animals , Chemistry, Pharmaceutical , Methods , Dermatitis , Drug Therapy , Allergy and Immunology , Drug Carriers , Chemistry , Drugs, Chinese Herbal , Chemistry , Pharmacokinetics , Emulsions , Chemistry , Female , Glycosides , Chemistry , Pharmacokinetics , Humans , Interleukin-4 , Allergy and Immunology , Interleukin-8 , Allergy and Immunology , Mice , Mice, Inbred ICR , Nanoparticles , Chemistry , Tripterygium , Chemistry
5.
Acta Pharmaceutica Sinica ; (12): 244-249, 2012.
Article in Chinese | WPRIM | ID: wpr-323050

ABSTRACT

Investigation of the pharmacokinetics of paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments by the skin-blood synchronous microdialysis coupled with LC/MS is reported in this study. The microdialysis systems were established by linear probes and concentric circles probes. In vivo recovery of paeonol in skin is (69.7 +/- 4.8) % and in blood is (51.6 +/- 7.2)%. The paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments were administered to rats. PBS (pH 7.4) served as perfused solution. The perfusion rate was 5 microL x mL(-1) and the microdialysis samples were collected every 20 min intervals. The paeonol concentration in perfused solution was determined by LC/MS. The results showed that paeonol microemulsion and microemulsion-based gels significantly raised the drug concentrations in skin more than that of paeonol ointments. The paeonol microemulsion-based gels has similar bioavailability as the paeonol ointments in blood, but its blood drug concentrations were steadier. The paeonol microemulsion-based gels may be developed into a new preparation for dermis eczema. The skin-blood synchronous microdialysis technique proved to be a new method for the pharmacokinetics study of transdermal delivery systems.


Subject(s)
Acetophenones , Blood , Metabolism , Pharmacokinetics , Administration, Cutaneous , Animals , Biological Availability , Chromatography, Liquid , Drug Delivery Systems , Emulsions , Gels , Male , Mass Spectrometry , Microdialysis , Rats , Rats, Sprague-Dawley , Skin , Metabolism , Skin Absorption
6.
Chinese Journal of Hepatology ; (12): 213-216, 2009.
Article in Chinese | WPRIM | ID: wpr-250012

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Capsule metadoxine in the treatment of alcoholic liver disease.</p><p><b>METHODS</b>A randomized double blind multicenter placebo-controlled clinical study was performed to evaluate the therapeutic effectiveness and safety of capsule metadoxine. Patients in metadoxine group received capsule metadoxine 500mg tid po. Patients in placebo group received placebo 2 pillows tid po. The treatment duration was 6 weeks. Patients were followed up 2 weeks after the treatment. Patients were visited once every 3 weeks during the treatment period. Clinical symptoms and liver function were evaluated in all the patients before treatment, at week 3, week 6 and 2 weeks after therapy. CT scan was done in some patients before treatment and at the end point of therapy.</p><p><b>RESULTS</b>254 patients were recruited in the study, 126 in metadoxine group and 128 in placebo group. Median ALT, AST, GGT level in metadoxine group were decreased from 80.0 U/L, 59.2 U/L, 123.0 U/L (before treatment) to 41.1 U/L, 36.0 U/L, 57.0 U/L (after 6 weeks therapy). The improvement in liver function was more significant in metadoxine group than in placebo group (P less than 0.05). For the patients who stopped drinking during the study, the total effective rate of improvement in liver function was 82.8% in metadoxine group, much higher than that in placebo group (55.7% , P=0.0000). For the patients who did not stop drinking during the study, the total effective rate of improvement in liver function was 65.4% in metadoxine group, which is not significantly higher than that in placebo group (44.8%, P=0.1767). The CT value ratio of liver to spleen was significantly improved in metadoxine group (P=0.0023), and there was no significant difference between the two groups (P=0.6293). The rate of adverse was 1.6% in both of groups.</p><p><b>CONCLUSION</b>Capsule metadoxine is an effective and safe treatment for alcoholic liver disease.</p>


Subject(s)
Administration, Oral , Adult , Aged , Alanine Transaminase , Blood , Alcohol Deterrents , Therapeutic Uses , Analysis of Variance , Aspartate Aminotransferases , Blood , Capsules , Double-Blind Method , Drug Combinations , Fatty Liver, Alcoholic , Blood , Drug Therapy , Pathology , Female , Follow-Up Studies , Humans , Liver , Diagnostic Imaging , Pathology , Liver Diseases, Alcoholic , Blood , Drug Therapy , Pathology , Liver Function Tests , Male , Middle Aged , Pyridoxine , Therapeutic Uses , Pyrrolidonecarboxylic Acid , Therapeutic Uses , Treatment Outcome , Ultrasonography , Young Adult , gamma-Glutamyltransferase , Blood
7.
Acta Pharmaceutica Sinica ; (12): 383-387, 2008.
Article in Chinese | WPRIM | ID: wpr-277844

ABSTRACT

To investigate the effect of cetirizine hydrochloride on the expression of neurokinin 1 receptor (NK-1R) and cytokines production induced by substance P (SP) in HaCaT cells (a human epidermal keratinocyte cell line) and dermal fibroblasts. The effect of cetirizine on the expression of NK-1R protein was detected by flow cytometry and Western blotting analysis. The modulation of cetirizine on the production of interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6 and IL-8 in HaCaT cells and fibroblasts was measured by ELISA. The results showed that cetirizine significantly inhibited the expression of NK-1R in HaCaT cells and fibroblasts. SP induced the production of IFN-gamma, IL-1beta and IL-8 in both cell types. Cetirizine 1-100 micromol x L(-1) inhibited SP-induced IL-1beta and IL-8 production in HaCaT cells and fibroblasts, while had no effect on the production of IFN-gamma in both cells. Both SP and cetirizine had no effect on the secretion of IL-6 in HaCaT cells and fibroblasts. These findings suggest that cetirizine may be involved in the treatment of SP-induced skin inflammation by inhibiting the expression of substance P receptor and regulation the production of IL-1beta and IL-8 in epidermal keratinocyte and dermal fibroblasts.


Subject(s)
Anti-Allergic Agents , Pharmacology , Cell Line , Cetirizine , Pharmacology , Fibroblasts , Cell Biology , Metabolism , Histamine H1 Antagonists, Non-Sedating , Pharmacology , Humans , Interferon-gamma , Metabolism , Interleukin-1beta , Metabolism , Interleukin-8 , Metabolism , Keratinocytes , Cell Biology , Metabolism , Receptors, Neurokinin-1 , Metabolism , Substance P , Pharmacology
8.
Article in Chinese | WPRIM | ID: wpr-307574

ABSTRACT

<p><b>OBJECTIVE</b>To establish a suitable dosage form for a traditional anti-anaphylaxis Chinese medicine of Kushen recipe, and investigate the effect of cutaneous permeation in vitro of the recipe.</p><p><b>METHOD</b>Techniques of extracting with ethanol and purifying with absorbent resin to obtain alkaloids from Kushen recipe were adopted, while volatile oil was extracted by steam distillation. The extraction was made to gel. The skin from SD rats' abdomen was used as permeability barriers. Then effects of permeation of the aqueous extraction, the purifying extraction and the gel were compared by Valia-Chien and Franz diffusion cell method. HPLC was utilized to quantitate the alkaloids in permeating liquid.</p><p><b>RESULT</b>In view of the permeation cumulation quantity, the permeation velocity and the lag time of the four kinds of alkaloids, the effect of permeation of purifying extraction was better than the aqueous extraction, and the purifying extraction gel surpassed both the aqueous extraction and the purifying extraction.</p><p><b>CONCLUSION</b>It was certified that the purifying extraction gel had improved the effect of cutaneous permeation of alkaloids, and it is the befitting dosage form for Kushen recipe to treat anaphylaxis disease in skin.</p>


Subject(s)
Administration, Cutaneous , Alkaloids , Pharmacokinetics , Animals , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Female , Gels , In Vitro Techniques , Quinolizines , Pharmacokinetics , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Skin , Metabolism , Skin Absorption
9.
Article in English | WPRIM | ID: wpr-285081

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association of polymorphisms of CDT1 and GMNN gene, two important genes participating in DNA replication, with the risk of sporadic breast cancer.</p><p><b>METHODS</b>Using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP) and the primer-introduced restriction analysis (PIRA)-PCR assay to genotype the CDT1 838G/A and GMNN 387C/A polymorphisms in a case-control study of 427 breast cancer cases and 477 cancer-free controls in a Chinese population.</p><p><b>RESULTS</b>No significant association of the CDT1 838G/A and GMNN 387C/A polymorphisms with the risk of breast cancer was found (adjusted OR:1.16, 95% CI:0.88-1.54 for CDT1 GA+AA genotypes and adjusted OR:0.90, 95% CI:0.67-1.21 for GMNN CA+AA genotypes). However, in the stratified analyses, a significant association of CDT1 GA+AA genotypes with breast cancer risk among subjects with family history of cancer was found (adjusted OR:2.21, 95% CI:1.20-4.09).</p><p><b>CONCLUSION</b>These findings suggest that the CDT1 838G/A and GMNN 387C/A polymorphisms may not play a major role in the etiology of breast cancer, but CDT1 variant may have a potential role only in genetically susceptible women.</p>


Subject(s)
Adult , Asians , Genetics , Breast Neoplasms , Ethnology , Genetics , Case-Control Studies , Cell Cycle Proteins , Genetics , China , Female , Geminin , Gene Frequency , Genetic Predisposition to Disease , Genetics , Genotype , Humans , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , Genetics , Polymorphism, Restriction Fragment Length
10.
Acta Pharmaceutica Sinica ; (12): 649-653, 2005.
Article in Chinese | WPRIM | ID: wpr-353456

ABSTRACT

<p><b>AIM</b>To investigate the effect of cetirizine hydrochloride on the expression of neuropeptide substance P (SP) in IgE-dependent triphasic cutaneous reaction induced by dinitrofluorobenzene (DNFB) in the ears of BALB/c mice.</p><p><b>METHODS</b>BALB/c mice were passively sensitized by intravenous infection of anti-DNP IgE monoclonal antibody 24 h before DNFB challenge. Skin reaction was elicited by applying DNFB to both sides of each ear of sensitized mice. Mice were treated with cetirizine (1 and 10 mg x kg)-1), ig). The ears were removed for pathohistological examination and immunohistochemical staining of SP at different designated times after challenge. The contents of SP in the skin of mouse ear were determined by radioimmunoassay (RIA).</p><p><b>RESULTS</b>The mice exhibited a triphasic cutaneous reaction with an immediate-phase response (IPR) at 1 h, a late-phase response (LPR) at 24 h and a very late-phase response (vLPR) at 7 days after challenge with DNFB. The expression of SP in different phases increased gradually. Cetirizine (1 and 10 mg x kg(-1)) was shown to significantly inhibit the ear swellings induced by the IPR (P < 0.01), while no obvious effect on the vLPR. The SP contents in ear skin of triphasic cutaneous reaction were decreased by cetirizine.</p><p><b>CONCLUSION</b>SP is considered to be involved in the pathogenesis of allergic dermatitis. Cetirizine hydrochloride can inhibit the expression of SP in IgE-dependent triphasic cutaneous reaction. It might be part of the mechanisms of anti-anaphylaxis of cetirizine.</p>


Subject(s)
Animals , Anti-Allergic Agents , Pharmacology , Cetirizine , Pharmacology , Dose-Response Relationship, Drug , Ear , Edema , Metabolism , Female , Hypersensitivity, Delayed , Metabolism , Hypersensitivity, Immediate , Metabolism , Immunoglobulin E , Allergy and Immunology , Mice , Mice, Inbred BALB C , Passive Cutaneous Anaphylaxis , Substance P , Metabolism
11.
Chinese Journal of Epidemiology ; (12): 165-168, 2004.
Article in Chinese | WPRIM | ID: wpr-342361

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the effectiveness and safety of mosapride on treatment of functional dyspepsia.</p><p><b>METHODS</b>Randomized controlled clinical trial was conducted and patients suffered from functional dyspepsia were included. 5 mg mosapride was given three times daily for 4 weeks in the treatment group. 10 mg domperidone was given three times daily for 4 weeks as control. Changes on symptom score, gastric empty or new occurring events were included as outcomes.</p><p><b>RESULTS</b>231 patients suffered from functional dyspepsia were selected by inclusion and exclusion criteria from August 15 to Oct 22, 1999. Of these, 108 (46.8%) were males, versus 123 (53.2%) females and 118 (51.2%) in the treatment group and 113 (48.9%) as controls. 222 (96.1%) patients were followed up. Results showed that the total efficacy rates in early satiety and abdominal distension were 84.5% and 90.1% in mosapride after the 2 weeks of treatment. Mosapride seemed to be more effective in improving symptoms of belching and heartburn than that in controls (P < 0.05). In 4 weeks, the total efficacy in improving symptoms of abdominal distention and belching showed more effective in mosapride than that in controls (P < 0.05). Decrease of symptoms score was more in mosapride than that in controls (P < 0.05). Mosapride was less effective in controls in improving the gastric empty in terms of proportion (46.2% vs. 25.9%, P = 0.020) and range (46.2% vs. 24.0%, P = 0.003). Side effects would include diarrhea, constipation, headache, dizziness, insomnia, skin scare and the like. There was no significant difference between the two groups (9.6% in mosapride vs. 14.0% in controls).</p><p><b>CONCLUSION</b>Mosapride was safe and effective in improving the symptoms and gastric empty of functional dyspepsia.</p>


Subject(s)
Adult , Benzamides , Therapeutic Uses , Dyspepsia , Drug Therapy , Female , Gastrointestinal Agents , Therapeutic Uses , Humans , Male , Middle Aged , Morpholines , Therapeutic Uses , Treatment Outcome
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