ABSTRACT
ObjectiveTo investigate the effects and molecular mechanism of ursolic acid on the proliferation and apoptosis of colorectal cancer cells. MethodThe proliferation inhibition rate of human colorectal cancer RKO cells treated with different concentrations of ursolic acid （0， 5， 10， 15， 20， 25， 30 μmol·L-1） was detected by cell counting kit-8 （CCK-8）， and the half maximal inhibitory concentration （IC50） at 24 h and 48 h was calculated. According to the IC50 of RKO cells treated with ursolic acid for 24 h， two concentrations were selected for subsequent experiments. The colony formation assay was used to detect the proliferation ability of the cells and flow cytometry was used to detect the apoptosis rate and cell cycle arrest after treatment of RKO cells with ursolic acid. After treatment of RKO cells with ursolic acid for 24 hours， the expression of B-cell lymphoma 2 （Bcl-2）-associated X protein （Bax） in RKO cells， Bcl-2 in Raji cells， PMA responsive gene in T lymphocyte （Noxa）， cyclin-dependent kinase inhibitor 1A （p21）， cyclin-dependent kinase inhibitor 1B （p27）， cyclin-dependent kinase 4 （CDK4）， protein kinase B （Akt）， phosphorylated Akt （p-Akt）， forkhead transcription factor O3a （FoxO3a）， and phosphorylated FoxO3a （p-FoxO3a） was determined by Western blot. ResultCompared with the blank group， the ursolic acid groups could inhibit the viability of RKO cells （P<0.05， P<0.01）， and the colony formation rates of RKO cells in the ursolic acid groups were reduced （P<0.05， P<0.01） in a concentration-dependent manner. The cells in the ursolic acid group （20 μmol·L-1） experienced cell cycle arrest， which increased in the early stage of synthesis， ie， the G0/G1 phase （P<0.05） as compared with the results in the blank group. Compared with the blank group， the ursolic acid groups （15 and 20 μmol·L-1） showed increased protein expression of p21 and p27， decreased expression of CDK4 protein （P<0.05， P<0.01）， and increased apoptosis rate， and the ursolic acid group （20 μmol·L-1） showed increased protein expression of Bax and Noxa and decreased expression of Bcl-2 （P<0.05， P<0.01）. In terms of mechanism， compared with the blank group， the ursolic acid group （20 μmol·L-1） down-regulated the expression of p-Akt protein and up-regulated the expression of p-FoxO3a （P<0.05， P<0.01）， and there was no significant change in the total protein of Akt and FoxO3a. ConclusionUrsolic acid can effectively inhibit the proliferation of colorectal cancer RKO cells and promote cell apoptosis， which may be related to the Akt/FoxO pathway.
ABSTRACT
Chinese medicine self-assembly nano-strategies（CSAN） is to utilize the self-assembly property of Chinese medicine components， so that the Chinese medicine components can self-assemble to form structurally stable nano-preparations through non-covalent interactions. The formation of Chinese medicine self-assembly nano-preparations is often a synergistic result of a variety of non-covalent interactions， and many Chinese medicine monomers are susceptible to self-assembly due to their structural characteristics， and the phenomenon of self-assembly of Chinese medicine is also common in the decoction of single or compound Chinese medicine， which has attracted the attention of researchers. It is found that CSAN can improve the solubility and bioavailability of active components in Chinese medicine， which is of positive significance for the development and application of insoluble components of Chinese medicine. The self-assembly phenomenon of Chinese medicine decoction is closely related to the therapeutic efficacy， and the study of self-assembly phenomenon of Chinese medicine will bring a new perspective for the explanation of the mechanism of Chinese medicine decoction. At the same time， traditional Chinese medicine（TCM） has unique advantages in the field of anti-tumor. The application of CSAN in the field of oncology can not only exert the anti-tumor effect of the active components of Chinese medicine directly， but also act as a natural nano-carrier to carry chemotherapy drugs for combination chemotherapy， improve the targeting of drugs， enhance the anti-tumor efficacy， and reduce the side effects of chemotherapy， which has excellent anti-tumor potential. The preparation method of Chinese medicine self-assembly nano-preparations is simple， low cost， and has better safety than traditional nano-preparations， which is conducive to the promotion of the clinical transformation of nano-preparations， and also helps to provide new strategies and perspectives for promoting the modernization of TCM. Therefore， based on a large number of researches in this field in recent years， this paper reviewed the formation mechanism， different assembly forms， formation conditions and stability of Chinese medicine self-assembly nano-preparations by searching databases such as China national knowledge infrastructure（CNKI）， PubMed， WanFang data and VIP， and summarized the application of CSAN in different tumor therapies， providing a reference for further research on CSAN.
ABSTRACT
Lung cancer is the highest mortality rate of malignancies in the world.Among them,non-small cell lung cancer (NSCLC) accounts for 85％.Epidermal growth factor receptor (EGFR) gene is one of the most common driving genes in NSCLC.The EGFR tyrosine kinase inhibitors (EGFR-TKIs) bring a breakthrough in the treatment for patients with EGFR gene-sensitive mutations.However,the drug resistance problem of EGFR-TKIs has been increasingly highlighted.So a drug for the patients accompanied by EGFR T790M positive mutation and along with progression in or after treatment with EGFR-TKI NSCLC is clinically urgent needed.Rociletinib is designed to address this unmet clinical need.While considering the non-superior effectiveness to the similar drugs in the market and the high risk of safety (hyperglycemia,QT prolongation and sudden death) of Rociletinib,the dosage was not accepted by the Food and Drug Administration (FDA).And Rociletinib did not make it to the market eventually.This paper discussed lessons learned from this case under review perspective for reference and inspiration.
ABSTRACT
The liver injury caused by drug and / or its metabolites is one of the most common reasons for drugs to be withdrawn or disapproved.Premarketing clinical evaluation of drug-induced liver injury (DILI) is extremely important to drug evaluation.Signals of DILI and Hyman's Law (Hy's Law),clinical evaluation and lessons of DILI were discussed to help developing new drugs.
ABSTRACT
TThe USA Food and Drug Administration (FDA) has an over 100-year history and is the most authority drug administration.During its past records,the most important thing for FDA is facing law enforcement challenges.However,FDA insists on improving legislation and finding the perfect mode of regulation.This paper introduced the history evolution,regulatory course,present office structure of FDA,Center for Drug Evaluation and Research (CDER),and Center for Biologics Evaluation and Research (CBER).The frustration and experience for FDA is well discussed.The legislation system is interpreted through historical events.To learn the developmental and regulatory history of USA food and drug administration is important to our drug administration for practicing the mission of protecting and promoting public health.
ABSTRACT
The multi-central clinical records retrospective survey for psoriasis vulgaris was carried out by collecting related information such as demographic, diagnostics, therapeutics, efficacy evaluation, nursing data, and so on. The Uygur medical differentiation classification standard about psoriasis vulgaris was established and it was divided into four types:abnormal Khan Hilit type, abnormal Sapra Hilit type, abnormal saltness Balgham Hilit type, and abnormal Sawda Hilit type, according to main symptom and secondary symptom feature. The disease efficacy evaluation standard was established based on score of surface area and severity of skin injury combining with the changes of main symptom and secondary symptoms. On the basis, guidelines for clinical research of new drugs of Uygur medicine used in the treatment of psoriasis vulgaris were formulated in accordance with the technical requirements and procedure of national center for drug evaluation.
ABSTRACT
Retrospective multi-center study on medical records of Uyghur medicine diagnosis and treatment program of eczema was done. Demography, diagnostics, therapeutics, efficacy evaluation and nursing data and other information were collated and analyzed. With analysis and summary of the primary and the secondary symptoms, eczema was divided into four types:blood corruption type (Ofunetlengen Kan Tiplik), blue colored yellow bile type (Zenggereng Sapra Tiplik), abnormal black bile type (Hayri Tabii Savda Hilitlik), and salty phlegm type (Shor Belgem Hilitlik). Uyghur Medicine syndrome differentiation and efficacy evaluation criteria were established. Skin itching, lesion shape, and lesion area integral of patients were scored before and after the treatment, respectively. According to the improvement in symptoms of Uyghur medicine syndrome and life quality of patients, and the internal environment change, evaluation criteria for the efficacy of disease symptom combination were established. On this basis, in accordance with the technical requirements of the national new medicine assessment technology, the study developed clinical research guidelines for the treatment of eczema with new Uyghur medicine.
ABSTRACT
Uyghur medicine has not yet had the clinical research guidelines consistent with Uyghur medicine theory for its new medicine. In this research, retrospective multi-center study on medical records of Uyghur medicine diagnosis and treatment program of stable angina was conducted. Data about demography, diagnostics, therapeutics, efficacy evaluation, and nursing were collated and analyzed. Uyghur medicine syndrome diagnosis indicators and their contribution to stable angina were identified, and Uyghur medicine syndrome differentiation criteria were established. Uyghur medicine established its primary and secondary disease syndrome and its symptoms quantization table entries for the syndrome elements of Uyghur medicine syndrome differentiation criteria. Then combined with symptoms of angina and ECG changes, nitroglycerin stop and decrement rate, evaluation criteria for the efficacy of disease symptom combination were established. On this basis, in accordance with the technical requirements of the national new medicine evaluation, the study developed clinical research guidelines for the treatment of stable angina with new Uyghur medicine.