Research progress of plant-derived vesicles and their biomedical applications / 药学学报

Plant-derived extracellular vesicles (EVs) are membranous vesicles secreted by plants, which include lipid bilayer as the basic framework and encapsulate various proteins, nucleic acid and other active substances. They play an important role in plant growth and development, tissue repair and self-defense. In recent years, extracellular vesicle-like nanoparticles (EVNs) are prepared from plant samples referring to the separation method of EVs and show unique functions. In this review, the above structures are collectively called plant-derived vesicles (PDVs). The biogenesis, separation and characterization methods, in vivo and in vitro properties of PDVs have been reviewed. The biomedical applications of PDVs as natural therapeutic agents and functional drug carriers are described, and finally some opinions on the existing problems and future prospect in this field are put forward.

Structural Chinese medicine: new research field on pharmacodynamic substance basis of traditional Chinese medicine / 中国中药杂志

The research on the pharmacodynamic substance basis of traditional Chinese medicine(TCM) is a key scientific issue for the inheritance and development of TCM. At present, a large number of remarkable achievements have been made in the field of chemical components in Chinese medicine, however, another important aspect, namely the physical structure and mode of action of the multi-component assembly of TCM, has not been clearly understood and deeply studied. From the bottleneck of restricting material ba-sic research, we objectively analyzed the common cause of the existing problems. Based on the new discoveries and advances of active substances from TCM emerging in recent years, we extracted and summarized the concept of structural Chinese medicine, elaborated the basic ideas, main features and research modes, hoping to provide theoretical and practical references for the study on the pharmacodynamic substance basis and other research fields of TCM.

Advances in research on antitumor preparations of cardiac glycoside / 药学学报

Cardiac glycoside is a class of steroidal glycosides with significant physiological activities to the heart. Several drugs had been approved for the treatment of heart failure and atrial fibrillation. In recent studies, the researchers have found that cardiac glycoside can selectively inhibit the proliferation of human tumor cells and has potent antitumor efficacy. Unfortunately, the poor solubility and severe adverse effects of cardiac glycoside hindered further clinical application in the field of anticancer. It is an effective strategy to solve the "drug-like" problem of cardiac glycoside by changing the pharmacokinetics and distribution in vivo and reducing the dosage and side effects by virtue of modern preparations technology and treatment scheme. In this review, a brief introduction of the developmental course and mechanism of cardiac glycosides in anticancer field was made, and recent research progress of cardiac glycosides preparations were summarized and discussed. Finally, the further research direction was prospected.

Protopanaxadiol derivative DDPU improvesbehaviorand cognitive deficitin AD mice involving regulation of both ER stress and autophagy / 中国药理学与毒理学杂志

OBJECTIVE To explore the potential effect and mechanisms of protopanaxadiol deriva-tive 1-(3,4-dimethoxyphenethyl)-3-(3-dehydroxyl-20(s)-protopa- naxadiol-3b-yl)-urea (DDPU) in the treatment of Alzheimer disease.METHODS ELISA assay was performed in both HEK293-APPswe and CHO-APP cells to demonstrate the efficacy of DDPU in reducing Ab level.SH-SY5Y,primary neurons and astrocyte cellswereused to study the regulation of DDPU against the signaling pathways involved in Aβ/ER-stress pathology. APP/PS1 transgenic mice wereusedto study the regulation of DDPU against ADL and cognitive deficits. APP/PS1 transgenic mice were randomly placed into three groups (n=10):The two 6-month transgenic groups were administrated with 30 mg·kg-1DDPU or vehicle and the 6-month non-transgenic group was administrated with vehicle for 100 days by intraperitonealinjec-tion.After 100-day administration,nest construction assay and Morris water maze(MWM)assay were applied to evaluate the daily living activities and cognitive abilities of the mice with continuous DDPU treatment. Upon completion of behavior assays, mice were euthanized, and the brains were removed and bisected in mid-sagittal plane.The right hemispheres were frozen and stored at-80°C,and the left hemispheres were fixed in 4% paraformaldehyde. RESULTS DDPU effectively improved learning and memory impairments in APP/PS1 transgenic mice, and the underlying mechanisms have been inten-sively investigated. DDPU reduced Ab production by inhibiting the PERK/eIF2a signaling-mediated BACE1 translation, while promoted Ab clearance as a PI3K inhibitor thus negatively regulating PI3K/AKT/mTOR signaling in promotion of autophagy.Moreover,DDPU also exhibited neuroprotective effect by attenuating ER stress. Therefore, all findings have clearly demonstrated the crosstalk between Ab and ER stress, and confirmed that targeting ER stress should be a potential target for innovative anti-AD drug development,while highlighted the potential of DDPU in the treatment of AD.

Correlation of the expression of III β-tubulin and MDR1 protein with biological features of non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the expression of III β-tubulin and MDR1 protein in patients with non-small cell lung cancer (NSCLC), and to clarify its clinical significance.</p><p><b>METHODS</b>Paraffin embedded tissues from 158 primary non-small cell lung cancers and para-cancerous lung tissues were investigated for the expression of III β-tubulin and MDR1 protein by immunohistochemistry, as well as in freshly-taken NSCLC tissues by Western blot. The relationship between the expression of III β-tubulin and MDR1 and the biological features of lung cancer was analyzed.</p><p><b>RESULTS</b>The positive rate of III β-tubulin and MDR1 protein expression in lung cancer tissues was 65.19% and 51.27%, respectively. Western blot analysis showed that the level of of III β-tubulin and MDR1 protein in NSCLC tissues was remarkably higher than that in normal tissues (P < 0.01). The expression of III β-tubulin in stage III-IV cases was significantly higher than that in stage I-II cases (P < 0.05), while the expression of MDR1 protein showed no significant difference (P > 0.05). The positive rate of III β-tubulin expression in well-moderate pathological grades was lower than that in poor ones. The positive rate of MDR1 expression in adenocarcinoma was higher than that in squamous cell carcinoma and large cell undifferentiated cancers (P < 0.01). The positive rate of expression of MDR1 protein and III β-tubulin was not correlated with sex, age, tumor size and lymph node metastasis (P > 0.05).</p><p><b>CONCLUSION</b>The expression of III β-tubulin and MDR1 may play an important role in the development and progression of human non-small cell lung cancer, and could be looked as an important index for judging the prognosis of lung cancer.</p>

Drug discovery based on classic natural products / 药学学报

We think the strategy of classic natural product-based drug discovery will be an effective way for us to develop new drugs with independent intellectual property. The strategy includes: to study the molecular mechanism of action of classic natural product with chemical genetics and chemical biology approaches firstly; then establish the proper in vitro bioassay or bioassay system based on its molecular mechanism for their pharmacodynamic evaluation; finally, study their structure-activity, structure-toxicity and structure-ADME properties with medicinal chemistry.