Latest ArticlesExtracellular 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.
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.
It is generally assumed that study of in vitro dissolution can reveal the in vivo behavior and bioavailability of a drug. The dissolution test indisputably plays a vital role in the research and development of pharmaceutical preparations as well as routine quality control of approved drugs. In order to develop an ideal dissolution method, the physicochemical properties of drug and the characteristics of its dosage form should be considered, and a proper dissolution condition be established to simulate the in vivo dissolution behavior of drugs. The new dissolution method should have the required characteristics of accuracy and durability, but also could distinguish pharmaceutic preparations with different quality. In recent years, there have been more and more reports on the establishment and verification of dissolution methods for oral solid dosage forms. However, there is very few review articles on the topic. According to the latest guidelines by domestic and foreign drug organizations, this review paper is prepared to summarize the most important skills and progress in the development of dissolution methods for oral solid preparations. The aim is to provide a reference for the development and validation of new dissolution methods.
Human carboxylesterase (CES) and arylacetamide deacetylase (AADAC) are important numbers of the serine esterase superfamily. They are involved in hydrolytic procedure of human endogenous cholesteryl esters, as well as drug metabolism, activation and detoxication. They are closely related to the personalized medication of drugs, especially for prodrugs. This review summarizes their structure and distribution, metabolic characteristics and research progress in recent years, which will provide a reference for new drug development and rational drug design.
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.
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.
Alcoholic liver disease (ALD) includes a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis and cirrhosis. According to epidemical statistics, ALD has been ranked as the second major cause of liver diseases in China. Many animal models have been made in the study of potential therapies. However, in most of the models, the pathological changes are not always consistent with those in patients. There are three widely used short-term animal models of ALD:the acute alcoholic liver injury model, Gao-binge steatohepatitis model and CCl4-alcohol diet induced liver fibrosis model. In this study, we evaluated the pathological responses of these models and compared the responses with the clinical parameters. The liver/body weight ratio was increased and liver histological lesions were induced in alcoholic groups in the three models, while the levels of biochemical parameters and inflammatory factors were affected by different type of treatments. In the acute alcoholic model, the mRNA levels of interleukin-6 (IL-6) and C-C motif chemokine receptor-2 (CCL2) were surprisingly decreased, which was consistent with the transcriptome profile in patients (P < 0.05), but the serum ALT and AST level, were not changed. In Gao-binge model, both AST/ALT and triglyceride levels were significantly induced by alcoholic consumption (P < 0.05), along with the gene expression levels of hepatic IL-6 and CCL2 (P < 0.05). These data were similar in tendency to the pathological indicators of hepatitis patients. In liver fibrosis model, although histological section indicated obvious fibrotic lesion and little lipid accumulations, other indexes were barely changed. In conclusion, the Gao-binge model induced similar pathological patterns to those of steatohepatitis patients. Gao-binge model might be ideal for study of ALD, especially alcoholic steatohepatitis. In addition, we also found that hepatic gene expression of CCL2 was impacted differently at various stages of ALDs, which can be considered as a potential biomarker.
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.
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.
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