Latest ArticlesD-galactose (D-gal)-induced aging model is widely used in the study of the pharmacodynamics of antiaging drugs. The model has a shorter life-span, disorders in learning and memory, reduced immune function and other aging characteristics. Regular and quantitative injection of D-gal solution to rats can produce symptoms of natural aging models that are used in screening of antiaging drugs, and their pharmacological activities. This paper provides a summary of the mechanism of rat model induced with D-gal solution. The methods of building and evaluation of the aging models are provided. The theoretical basis is included to facilitate the subsequent research and experiment in the mechanism study of aging and antiaging medicines.
Diabetic neuropathic pain (DNP) is the most common chronic complication of diabetes mellitus, significantly affecting people's quality of life. Studies have indicated that ion channels play a very important role in the occurrence of DNP. This review provides a summary in the role of ion channels in diabetic neuropathic pain and treatment strategies for diabetic neuropathy targeting ion channels.
In recent years, owing to the abuse of antibiotics, the widespread of resistant bacterial strains became a serious threat to public health. This status demands development of new antibacterial agents with novel mechanisms of action. The reason for the limited new antibacterials is the small number of effective therapeutic targets, which cannot meet the current needs for the multiple drug-resistant treatment. Screening for new targets is the key step in the development of novel antibacterial agents. Peptidoglycan is the main component of the cell wall of bacteria, which is essential for survival of pathogenic bacteria. Within the biochemical pathway for peptidoglycan biosynthes is the Murligases, described in this review as highly potential targets for the development of new classes of antibacterial agents. This review provides an in-depth insight into the recent developments in the field of inhibitors of the Mur enzymes (MurA-F). Moreover, the reasons for the lack of candidate inhibitors and the challenges to overcome the hurdles are also discussed.
Population pharmacokinetics is an emerging discipline developed from the combination of classical pharmacokinetic compartment model and statistics principles, which has been received more and more attention in recent years. Population pharmacokinetics plays important roles in all stages of new drug research. In the early preclinical phase, population pharmacokinetic analysis can help to achieve the preliminary prediction of parameters from animal to human, optimize clinical trial designs, and shorten the time required for new drugs from laboratory to clinical trials. In clinical trials and applications stage, population pharmacokinetic research can help researchers investigate the related covariates that affecting pharmacokinetic behavior of patients comprehensively, and find potential drug-drug interactions in clinical. In addition, population pharmacokinetics has a unique advantage in pediatric drug development due to its strong analysis ability of sparse data. This paper provides a summary on the history and methods of population pharmacokinetics, and the application in new drug discovery and development.
The pharmacological activities of natural glycosides are closely related to the polyfunctional sugar moieties. Modification of active natural products by glycosylation can change the stereochemical configuration, improve the solubility, tune up the activities and change pharmacokinetic properties for higher efficacy and better selectivity. Compared with the common D-glucose, D-allose, a C-3 epimer of D-glucose rarely exists in nature, but it plays an important role in food, health, medicine, and so on. It is not easily metabolized in the living organisms, but can be used as a safe and low-calorie sweetener. The natural allopyranosides are absolute conjugation forms which are same as other glucopyranosides and rhamno-pyranosides with a broad array of biological activities. This article summarizes the major progresses made in phytochemistry and biological activity studies of these compounds. Structure-activity relationship analyses of partial anti-tumor and anti-diabetic allopyranosides were performed regarding the data reported in the literatures. These insights may provide a theoretical and experimental reference for the discovery of new drug and drug design based on allopyranosides.
This study was conducted to test the effects of schizandrin B (Sch B) on clozapine (CLZ) induced chronic liver injury in mice and the mechanism of action, and this may provide a new approach for clinical prevention of CLZ-induced side effects. The CLZ was given to mice for three weeks alone or co-administration with Sch B. The changes of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and antioxidation indexes superoxide dismutase (SOD), malonic dialdehyde (MDA), glutathione (GSH) and liver histological evaluation were determined. Expression of Nrf2 was assayed in hepatic cells by immunohistochemical staining and Western blotting. The changes of relative gene expression of NAD (P) H:quinone oxidoreductase l (NQO1) and heme oxygenase 1 (HO-1) were assayed by real-time Q-PCR. The results showed that pretreatment with a lower dosage of Sch B (25, 50 mg·kg-1) prevented CLZ-induced liver injury as indicated by the reduced levels of ALT, AST and ALP, and the preserved activities of SOD, GSH and inhibiting MDA. It was shown that Sch B could up-regulate Nrf2 expression leading to nuclear accumulation of Nrf2 to induce oxidative response genes such as NQO1 and HO-1. These results suggest that Sch B could protect against liver injury induced by CLZ via the activation of the Nrf2/ARE signal pathway in a dose-dependent manner.
This study was designed to explore the effect of apigenin (Api) on dendritic cell (DCs) maturation and function in murine spleen cells. The single spleen cell was isolated, and then cultured with lipopolysaccharide (LPS) in the present and absence of apigenin. After 24 h, the toxicity of Api and the T cell proliferation were determined by CCK8 kit. In addition, we collected the cell-free supernatants to measure cytokine production using ELISA, collected the cells to determine the DC maturation using flow cytometry. Finally, we purified Api and/or LPS-treated CD11c+ DCs which were pulsed with ovalbumin (OVA)323-339 and then were adoptive transferred into C57BL/6 mice to detect the OVA323-339-specific T cell proliferation and T helper (Th1) and Th2 cell secreting IFN-γ and IL-4 production, respectively. We found that Api did not affect splenocyte viability, but inhibited the production of pro-inflammatory cytokine IL-1β, IL-6 and TNF-α, not anti-inflammatory cytokine IL-10. In addition, Api inhibited the expression of co-stimulatory CD80, CD86 and MHCII of CD11c+ DCs. Finally, compared to LPS+OVA DCs group, DCs from Api and LPS co-treated splenocytes (Api+LPS+DCs) impaired OVA323-339-specific T cell proliferation and the production of IFN-γ and IL-4 in CD4+ T cells, which had the similar responses with OVA+DCs. These data suggest that Api exhibits anti-inflammatory properties via inhibiting DC activation and function, as a new immune-modulator, which may induce immune-tolerance with a benefit to those with chronic inflammation.
Transglutaminase (TG) posttranslational modification of antibody permits more precisely conjugating. Based on the amino acid sequence of an anti-CD24 antibody (cG7), this article is aimed to generate a deglycosylated cG7 mutant (cG7Q). Firstly, we introduced additional glutamines at position 297 (N297Q) by site-directed mutagenesis, and then transfected the recombinant plasmids into CHO-s cells via electroporation method and screened by Dot blot assay. Subsequently, cG7Q was expressed and purified through Protein A affinity chromatography, further identified by SDS-PAGE electrophoresis and Western blot. Its affinity was detected with surface plasmon resonance and flow cytometry assay, and ADCC effect was determined by lactate dehydrogenase (LDH) release. Eventually, a cG7 mutant, cG7Q was successfully expressed with sequence-specific conjugation sites for further study.
With the method of fluorescence polarization (FP), we screened small molecule inhibitors for PLK1 PBD to identify the lead compounds for antitumor drugs. FP led to the identification of a potent hit, F083-0063, whose inhibition rate was (99.7±0.4)% at 10 μg·mL-1. The IC50 was calculated to be 1.9±0.1 μmol·L-1 using Graphpad Prism 5. The effect of the compound on cells' multiplication was measured by MTT assay which showed that F083-0063 inhibited the proliferation of many tumor cell lines. Flow cytometry analysis indicated that the F083-0063 promoted cell apoptosis and induced cell G2/M arrest. Migration abilities of cells, evaluated using scratch test, increased significantly in the presence of F083-0063 with the mi-gration rate as low as (37.6±0.7)% at 20 μmol·L-1. Molecular linkage technique found F083-0063 had good affinity with PLK1 PBD. The results of Western blotting showed that the expression of cyclin-dependent proteins was increased after treatment with F083-0063. In summary, F083-0063 has an antitumor activity and is expected to be an antitumor lead compound targeting PLK1 PBD.
This study was conducted to design and synthetize highly efficient, specific, non-resistant small MEK inhibitors. Based on active small molecules which have been reported, we studied the action mode with MEK protein using Autodock 4.2, generated innovative and feasible design method, designed novel small MEK protein inhibitors with a reference to molecular modeling and docking. The anti-tumor activities of four kinds of cells including MCF-7, PANC-1, SY5Y, A549 were tested with MTT method in vitro. The structure of 10 new small molecules has been determined with 1H NMR and 13C NMR. The compounds 4, 6, 7, 8, 10 had high antitumor activities, the compounds 1, 3, 5 also showed good activity, and the compounds 2, 9 showed cell selectivity in killing tumor.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
