A large number of epidemiological data have shown that the high-density lipoprotein cholesterol level is negatively related to atherosclerotic cardiovascular disease, suggesting that high-density lipoprotein may have the effect of anti-atherosclerosis. It may play the role of anti-atherosclerosis, through the promotion of cholesterol reverse transport, anti-inflammatory, antioxidant, and against thrombosis and fibrinolysis and so on. Among them, reverse cholesterol transport which is mainly regulated by apolipoprotein A-I, ATP-binding cassette transporter 1, liver X receptor and cholesteryl ester transfer protein, may play a major role in the maintenance of cholesterol homeostasis and reversing the course of atherosclerosis. These regulatory factors may be potential targets in high density lipoprotein-based drug discovery. In this review, these key proteins are discussed for the current status of small molecule drugs against atherosclerosis.

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.

The study is aimed to investigate the anti-depressant effect of puerarin in rat model of depression induced by chronic unpredictable mild stress (CUMS) and to explore the relevant mechanism. We established the depression rat model using CUMS. Rats were randomly divided into control, CUMS model, CUMS +fluoxetine (10 mg·kg^-1) and CUMS +puerarin (50, 100, 200 mg·kg^-1) groups. Drugs or vehicle were administrated after stress induction for 21 days. Open-field test (OFT), sucrose preference tests (SPT) and forced swim test (FST) were used to evaluate the anti-depressant effects of puerarin. The reactive oxygen species (ROS), prostaglandin E₂ (PGE₂) level, superoxide dismutase (SOD) and catalase (CAT) activities in hippocampus were determined by ELISA. Expression of IL-1β, TNF-α, and IL-10 was measured by qRT-PCR and Western blot analysis. Behavioral test suggests that crossing score, rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than the control group (P < 0.01), while immobility time in FST was significantly increased (P < 0.01). Compared with those in control group, the ROS and PGE₂ level increased significantly (P < 0.01), SOD and CAT activities were decreased significantly (P < 0.01), the mRNA and protein level of IL-1β, TNF-α, and IL-10 were increased significantly (P < 0.05 or P < 0.01) in rats of CUMS. Puerarin and fluoxetine ameliorated those changes induced by CUMS. Puerarin improved the depression-like behaviors of rats induced by CUMS, and the mechanism may involve in the antioxidant and anti-inflammatory effects.

This study was designed to explore the antidepressant mechanism of Bupleuri radix through establishing the active components-targets network and protein interactions network and analyzing the functions and pathways of targets. The main active ingredients of Bupleuri radix were obtained by TCMSP, literature study and the results of our own work. Based on the DRAR-CPI, GeneCards and OMIM were used to predict and screen the active components of Bupleuri radix. The Cytoscape software was used to construct the active components-targets network of Bupleuri radix. The protein interactions network was constructed using the String database and Cytoscape software. The relation of the main active ingredients and targets were validated by Systems Dock Web Site. The GO and KEGG pathways involved in the targets were analyzed by DAVID. Using DisGeNET database to attribute the type of targets. The results showed that 15 active components and 50 targets of Bupleuri radix were involved. The network results showed that the process of metabolism, regulation and response to stress were mainly involved, by adjusting the PI3K-AKT, MAPK, Rap1, Ras, FoxO, neurotrophin and other signaling pathways to play its antidepressant effect. This study reflects the characteristics of multicomponents-multi-targets and multi-pathways of Bupleuri radix, which provides new ideas and clues for further research on the mechanism of anti-depressive effects of Bupleuri radix.

Plasma stability plays an important role in the druggability of lead compound. Improving the plasma stability of compounds by structural modification can lead to good pharmacokinetic and pharmacodynamics properties. This review provides a summary of varieties of structure modification strategies for improving plasma stability including bioisosterism, increasing steric hindrance, ring closure, scaffold hopping and etc.

Ubiquitination and deubiquitination play important roles in the regulation of protein stability and function. Deubiquitinating enzymes (DUBs) are involved in the regulation of survival, migration and proliferation of cancer cells, by participating in a variety of signaling pathways. Most of the DUBs promote the malignant transformation and progression, while the others may function as tumor-suppressors. Given the central roles of DUBs in tumorigenesis and malignant progression, some of these enzymes have been regarded as promising anti-cancer targets. This paper reviews the recent advances in tumor-related DUBs and inhibitors.

Berberine is an original antibacterial drug in China, and is widely used for its diverse biological functions. It is first used in clinic to treat intestinal bacterial infections. Berberine has different inhibitory effects on various microorganisms, but the effect is very weak with the minimum inhibitory concentration over 64 μg·mL^-1 in most of the study bacteria. The effect is better for Bacillus dysteriae, which is one aspect of its selectivity. At the same time, because of the poor absorption of berberine in oral administration, it is retained in the intestine to reach a high concentration, which provides a basis for tissue selectivity in the treatment of intestinal bacterial infections. In this paper, we reviewed the antibacterial action, mechanism, clinical application of berberine, in order to provide a clue for the future direction of berberine research.

Carboxylesterases (CESs) belong to the esterase family, which are mainly responsible for catalyzing metabolism of a variety of drug as well as endogenous and exogenous compounds. CESs are widely distributed in the body, mainly expressed in lung, liver, intestine, kidney, skin epithelial cells, etc. There are significant species differences in the expression of CESs, which results in the difference on the drug metabolism with genetic polymorphism. In this paper, an overview of the classification and distribution, physiological function and mechanism, species differences and gene polymorphism of CESs are provided for the research of CESs and drug design.

The study is aimed to evaluate the anti-HIV-1 effect of chloroquine in combination with antihuman immunodeficiency virus (HIV) drugs, and inhibition of plasmacytoid dendritic cells (pDC) activation and type Ⅰ interferon (IFN-I) production by Toll-like receptor 7 (TLR7) agonist stimulation. We investigated the anti-HIV-1_ⅢB, HIV-1_KM018 activity of chloroquine and chloroquine combined with rategrivir (RAL), enfuvirtide (T-20), indinavir (IDV) and efavirenz (EFV) in vitro by luciferase activity assay system and ELISA method for p24 antigen. We measured the effect of chloroquine on the activation of pDC in combination with RAL and IDV, respectively. Quantitative PCR was used to evaluate the activity of chloroquine in combination with RAL and IDV in the upregulation of interferon (IFN)-α and IFN-β. Chloroquine showed less cytotoxicity to C8166, TZM-bl and PBMC cells, and the 50% cytotoxic concentration values were 85.02 ±0.28, 73.67 ±5.10 and 91.84 ±4.10 μmol·L^-1, respectively. The anti-HIV-1_ⅢB activity of chloroquine combination with RAL, T-20, IDV and EFV were moderate in synergy, strong in synergy, additive and moderate antagonism, respectively. The anti-HIV-1_KM018 activity of chloroquine in combination with RAL, IDV were moderate synergy, minor synergy. There was no significant difference between the chloroquine monotherapy and chloroquine combined with RAL, IDV in the down-regulation of pDC activation and IFN-α, IFN-β expression levels. We have found that chloroquine combined with different anti-HIV drugs represent different degrees of synergism, antagonism or additive anti-HIV-1 effect. Chloroquine in combination with RAL and IDV did not have influence on the inhibitory effect of chloroquine on pDC activation and type Ⅰ interferon secretion induced by TLR7 agonist. The results suggest that chloroquine may be used to enhance the therapeutic activities of anti-HIV medicines.

Beads, a novel drug delivery system self-assembled by cyclodextrins (CDs) and oil, has potential applications in the solidification of oil drugs and improving the bioavailability of lipid-soluble drugs. However, very few researches were dedicated to the mechanism of beads formation. In this study, three-dimensional structures of beads were visualized and investigated using synchrotron radiation X-ray microcomputed tomography (SR-μCT). The structural changes of beads attributed by drying process were analyzed and confirmed via visualization results of SR-μCT. Productively, it was proposed that Pickering emulsion droplets obtained during beads formation process were spatially localized orderly. Moreover, the effects of loading lipid soluble drug, namely, vitamin K₁, on the structural changes of beads were also analyzed. It is well known that the surface tension of oil phase could be changed by the addition of lipid soluble constituents. It was reasonable that the three-dimensional structure of beads might be altered during the drug loading of vitamin K₁ into the beads. However, although the morphologies of beads were changed to some extent, the ordered Pickering emulsion droplets during the process of beads formation was successfully illustrated based on the SR-μCT results. Conclusively, according to the three-dimensional structural analysis of the beads, this study revealed the organized architecture for Pickering emulsion droplet assembly and beads formation in cyclodextrin semi-inclusion complex, which significantly complements the formation mechanism of beads, and provides a structural basis for the further study of beads.