Latest ArticlesHistone H3 lysine 79 (H3K79) methyltransferase DOT1L plays an important role in the activation and maintenance of gene transcription; it is also essential for maintenance of embryonic development, as well as the normal function of hematopoietic system, heart and kidney. However, the over expression of DOT1L is associated with the occurring and progress of numerous malignant tumors, so more and more attention has been paid to DOT1L. Therefore, it is of great significance to study and develop inhibitors of DOT1L. The inhibitors could serve as a tool in the investigation of the biological function, and have the potential to be developed into novel anti-cancer agents in the anticancer therapy. This paper mainly describes the structure and function of DOT1L, the relationship between DOT1L and tumors as well as the latest research progress of DOT1L inhibitors; with expect to provide some useful references for the subsequent research.
The response surface method was used to evaluate the concentration range, property and degree of Scutellaria (HQ) and Coptis (HL) herb pair on improvement of glucose and lipid metabolism in this paper. Type 2 diabetes mellitus (T2DM) was induced in rats by low a dose of streptozotocin (STZ) in combination with high-fat diet feeding. The rats were administered with HQ-HL extract pairs at different ratio (1:0, 3:1, 2:1, 3:2, 1:1, 2:3, 1:2, 1:3, 0:1). To investigate the influence of herb pair extracts on glucose and lipid metabolism of T2DM rats, the multi index synthetic index method was adopted to integrate the indexes, then the response surface method was applied to analyze the integration results. The ratio of HQ and HL from 3:1 to 1:3 showed a synergistic effect (with the value between -0.2 and -0.8). Especially, when the proportion was between 3:2 and 1:3, herb pair extracts possessed stronger synergistic effects (value:-0.8). The high dose of HQ-HL with the ratio of 1:1 exhibited the strongest synergistic effect.
Apoptosis is an important self-stabilizing mechanism of multicellular organisms, which plays a vital role in the development of normal living organisms and the maintenance of tissue homeostasis. The abnormalities in apoptosis often lead to body lesions including tumors. Studies have shown that Bcl-2 protein with anti-apoptosis activity is an important target in the treatment of cancer. After nearly two decades of efforts, many small molecule Bcl-2 inhibitors have been discovered to induce cell apoptosis. The small-molecule Bcl-2 inhibitor, venetoclax, was developed based on fragment-based drug design strategy and approved by the FDA in 2016 for clinical application. This agent is the first approved small-molecule drug inhibiting Bcl-2 through protein-protein interaction to induce cell apoptosis. The achievement of venetoclax benefits from a combination of drug discovery technologies and represents a milestone in the history of drug discovery. In this review we will introduce the current progress in Bcl-2 inhibitors.
The difficulty to eradicate the HIV-1, off-target effects together with the rapid emergence of multidrug-resistant strains have created an urgent need for more potent and less toxic therapies against other targets of HIV virus. From the point of view of medicinal chemistry, we summarizes and discusses current endeavours towards the discovery and development of novel inhibitors with various scaffolds or distinct mechanisms of action, and also provides examples illustrating new methodologies in medicinal chemistry that contribute to the identification of novel antiretroviral agents.
This study was designed to test the effect of short-term high-fat diet feeding on the cognitive impairment in a rat model of Alzheimer's disease. After establishment of Alzheimer's disease model, the rats were fed on a high-fat diet, and subjected to water maze (Morris water maze, MWM) behavioral test for learning and memory ability. Western blot was used to detect the expression of caspase-1 pathway. The results showed that short-term high-fat diet could alleviate the damage of okada acid in Morris water maze. The mechanism may be mediated by the regulation of the NLRP3/caspase-1 signaling pathway, which alleviates neuronal damage, resulting in a protective effect.
Extracellular acidity has been associated with many pathological states, such as cancer, ischemic stroke, neurotrauma and infection, which makes it an effective target for therapy and diagnosis of such diseases. As a polypeptide vector, pH low insertion peptides (pHLIPs) are endowed with high sensitivity to extracellular acidic environment, which can insert the membrane and deliver payload to pathological cells in a pH dependent manner. Here, theranostic applications of pHLIP in disease, are reviewed in two aspects:pHLIP-mediated single-molecule transporter and nano-sized carrier.
The flower bud of Tussilago farfara L. has been commonly used in the treatment of cough, bronchitis and asthmatic disorders in the Traditional Chinese Medicine. In Europe, the leaves were also used as herbal drugs with similar pharmacological activities. In order to utilize the leaves, it is important to conduct the chemical comparison between the flower buds and the leaves. In this study, ultra high liquid chromatography (UHPLC) coupled with Q Exactive high resolution mass spectrometry (HR-MS) was used to compare the chemical composition of the flower buds and leaves of T. farfara L. forty three metabolites were identified by the combination of targeted and untargeted approach. The results suggest that the sesquiterpenes, such as tussilagone and 7β-(3'-ethyl-cis-crotonoyloxy)-1α-(2'-methylbutyryloxy)-3(14)-dehydro-Z-notonipetranone were higher in the flower buds. While the phenylpropanoids, such as cholorgenic acid and isochlorogenic acid were higher in the leaves. The flavonoids, such as hyperin and quercetin exhibited no difference between the flower buds and leaves, while the rutin and kaempferol were higher in the flower buds. The leaves and flower buds had similar chemical components, and the phenylpropanoids, which were closely related with the antitussive and expectorant activities, were found at higher concentrations in the leaves. The results presented here laid the basis for the rational utilization of the leaves of T. farfara L.
The purpose of this study was to prepare T7 peptide modified vincristine loaded low density lipoprotein (T7-LDL-VCR) nanoparticles to penetrate through blood brain barrier for targeting the brain tumor cells.Firstly, the low density lipoprotein (LDL) nanoparticles were extracted and separated from human serum by density gradient centrifugation method, and then was loaded into the nanoparticle's lipid core by the dry film method, T7 peptide was covalent modified on the surface of the nanoparticles.T7-LDL-VCR was characterized by particle size, entrapment efficiency and peptide attachment efficiency.The fluorescent probe DiR was used to track the brain biodistribution of T7-LDL-VCR in mice bearing intracranial C6 glioma by means of in vivo imaging.The therapeutic effect of nanoparticles was observed with magnetic resonance imaging (MRI).Finally, relative tumor volume and survival curve were determined in mice.The results showed that the mean size of the prepared T7-LDL-VCR nanoparticle was about 30 nm, encapsulation efficiency was 30.1%, and peptide attachment efficiency was 63.88%.As expected, the prepared preparation has good brain targeting and good effect on the treatment of glioma in mice:the relative tumor volumes of T7-VCR-LDL, LDL-VCR and VCR were 30%, 51.50% and 79.25%, respectively; the median survival time (36 days), which was 2, 1.85 and 1.38 fold higher than that of physiological saline, free VCR and LDL-VCR, respectively.This study suggests that dual modified hposomes possessed a better ability penetrating the blood brain barrier to target the brain tumor with significant antitumor activities.
This study was aimed to explore the pharmacokinetics of epiberberine, jatrorrhizine, coptisine, palmatine, berberine of Jiaotai pill in the normal and depressed rats. According to 'Katz' method, the model of chronic unpredictable mild stress (CUMS) was established. The extract of Jiaotai pill was orally administered to rats, and the blood samples were collected via the the oculi chorioideae vein according to the time schedule. The concentrations of epiberberine, jatrorrhizine, coptisine, palmatine, berberine in rat plasma were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by DAS1.0 software. Compared with normal rats, the Cmax of palmatine, coptisine, berberine and jatrorrhizine in Jiaotai pill in depressed rats were 1.99, 2.14, 2.3, 1.82 times than the normal group, while the AUC0−t were 1.23, 1.25, 1.29, 1.46 times and the AUC0−∞ were 1.21, 1.25, 1.30, 1.43 times, which were significantly different.
The antioxidant activities of Vleriana jatamansi Jones were investigated and the relationship between the antioxidant effect and the chemical structure was explored. The free radical scavenging test, 2, 2-diphenyl-1-picrylhydrazyl (DPPH•), was used to evaluate the antioxidant activities of the extracts of Vleriana jatamansi Jones with 0−100% menthol as extraction solvents. The polar and nonpolar HPLC conditions were conducted to isolate the main chemical compositions. The DPPH• tests were used in analysis of the free radical scavenging activities. Under polar HPLC separation conditions, 5 kinds of compounds were detected:chlorogenic acid, 3, 5-dicaffeoylquinic acid, 4, 5-dicaffeoylquinic acid, hesperidin, and coffeic acid; under nonpolar HPLC separation conditions, acevaltrate, 1β-acevaltrate and valtrate were founded. Chlorogenic acid, 3, 5-dicaffeoylquinic acid, and 4, 5-dicaffeoylquinic acid presented high DPPH• free radical scavenging activities. The results of antioxidant activity suggested that the coffee acyl from chlorogenic acid-like compounds had a high DPPH• free radical scavenging ability. Our investigation indicated that structure of the ortho hydroxyl phenol of chlorogenic acid-like compounds play a significant role in antioxidant activities. In addition, this work can also provide method and theory reference for improving the antioxidant activities of Vleriana jatamansi Jones.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
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
