Latest ArticlesPsoriasis, bringing great trouble to patients' life, is a common chronic immune skin disease which is relapsed and difficult to cure. Further understanding of the pathogenesis of psoriasis will be benefit for potential drug targets and the development of therapeutic drugs. In recent years, "interleukin-23/T helper17 (IL-23/Th17) cell axis" has attracted more and more attention in the pathogenesis of psoriasis. Some drugs targeting the cell axis have also been successfully listed in the market to improve psoriasis and achieved good results. This review focuses on the "IL-23/Th17 cell axis" system to elaborate the role of a variety of immune cells involved in the pathogenesis of psoriasis, such as dendritic cells, macrophages, neutrophils and T cells, and summarizes multiple therapeutic antibodies targeting this cell axis in the treatment of psoriasis. In addition, this review also summarizes the current small molecule drugs for the treatment of psoriasis.
Galectin-3 is an endogenous β-galactoside-binding lectin widely distributed in the human body, and it plays an important role in various functions such as cell proliferation, differentiation, apoptosis, cell adhesion, immune response and signal transduction. Accumulating evidence has shown that galectin-3 is involved in the occurrence and development of respiratory diseases, including idiopathic pulmonary fibrosis, lung cancer, pulmonary hypertension and bronchial asthma. This review summarizes and analyzes the research progress on galectin-3 in the above respiratory diseases in order to clarify its role and mechanism, and to provide new ideas for clinical treatment.
The incidence and mortality of chronic obstructive pulmonary disease (COPD) and lung cancer are increasing year by year, which are causing massive social and financial burdens around the world. An increasing number of investigations indicate the possibility of COPD transforming into lung cancer. The pathogenesis of these two diseases have some common aspects, such as epithelial-mesenchymal transition, chronic inflammation, DNA damage, impaired immune system, oxidative stress and tumor angiogenesis, which are heavily complicated. This review summarizes the epidemiological connection between COPD and lung cancer, the molecular-level transformation mechanism as well as the therapeutic strategy. Exploring the transformation mechanism and related signaling pathway of COPD to lung cancer can contribute to block the risk factors for the transformation and provide guidance for the novel drug development and drug therapy.
Bile acids (BAs) are increasingly being appreciated as signaling molecules. Studies have shown that BAs regulate glucose and lipid metabolism mainly through the intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5). FXR and TGR5 are highly expressed in the intestine. This article summarizes the synthesis, circulation, and regulation of BAs, as well as the effects of BAs on glycolipid metabolism through activation of liver FXR and inhibition or activation of intestinal FXR and TGR5. Furthermore, we illustrate the molecular mechanism of BAs on glycolipid metabolism by the relevant signaling pathways, including small heterodimer partner (SHP), fibroblast growth factor 15/19 (FGF15/19), ceramide and glucagon like peptide-1 (GLP-1). This review may serve as a reference for basic and clinical studies.
Autophagy is a widespread and unique degradation process in eukaryotic cells. When cells are under various stress conditions such as nutritional deficiencies, growth factor deficiencies or hypoxia, autophagy will be initiated to maintain the stability of the internal environment and ensure normal proliferation and differentiation. At present, research on autophagy-related targets is mostly focused on tumor cells. In contrast, research on fungal autophagy targets is still limited. Autophagy plays an important role in growth, development and morphological changes of fungal cells, suggesting that research on fungal autophagy as a drug target should be useful. This article reviews the signal regulation and detection strategies for autophagy in fungal cells, and provides a research basis for the screening of antifungal drugs targeting autophagy-related proteins.
Medicinally active molecules are those that have pharmacological effects. Research on protein targets of these molecules not only clarifies their mechanism of action, but also deepens our understanding of biological systems. Here we review recent advances in protein targets of drugs used in clinical practice or in preclinical research. They have various functions including anti-inflammatory, anti-malarial, anti-tumor and other biological activities. Activity-based protein profiling (ABPP) and cellular thermal shift assay (CETSA) are two useful methods to identify the protein targets of small molecules. ABPP depends on a derivative active molecule probe to pull down the protein targets to reveal the interaction mechanisms between the active molecules and targets. Drug target engagement also can be assessed by means of CETSA based on ligand-induced changes in protein thermal stability. In the CETSA approach, the active molecules do not need to be chemically modified. Combining the CETSA method with quantitative mass spectrometry is an effective approach to study the effect of compounds on the thermal profile of a cellular proteome and identify the protein targets.ABPP and CETSAcan be complementary and effectively clarify the protein targets. The study of protein targets will help reveal the mechanism of action of medicinal molecules, reveal toxic mechanisms and aid in the discovery of new medicinal targets to promote the process of drug development.
Reactive oxygen species (ROS) which were partial metabolites of oxygen are highly reactive. Different concentrations of ROS have different effects on tumor development. Tumor cells have a high level of reactive oxygen species. The antioxidant system of tumor is in highly activated state, and thus modulation of reactive oxygen species levels could be an effective strategy to target cancer cells. Treatment with small molecules that disrupt the redox balance can kill tumor cells first. This paper outlines the main ideas of developing anti-tumor drugs based on reactive oxygen species regulation, and summarizes the representative drugs and research progress according to the mechanism of action, in an effort to suggest potential reference and ideas for developing antitumor drugs based on reactive oxygen species regulation.
Snow lotus is a medicinal plant with a wide range of pharmacological activities. It has been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in traditional medicine. This review summarizes the bioactive components in six species of snow lotus including flavonoids, lignans, phenolic compounds, phenylpropanoids, and sesquiterpenes present in Saussurea involucrate (SI), Saussurea obvallata (SO), Saussurea laniceps (SL), Saussurea medusa (SM), Saussurea stella (SS) and Saussurea tridactyla (ST). We review the pharmacological and related molecular mechanisms by which these components exert antineoplastic, anti-inflammatory, and antioxidant effects and promote lipid catabolism, and provide a reference for the future study of the traditional Chinese medicinal chemistry and pharmacological activities of snow lotus.
Obesity is an important cause of a panel of metabolic diseases, such as hypertension, hyperlipidemia, arteriosclerosis, type 2 diabetes and various cancers. Discovery of anti-obesity agents has always been a hot spot in the field of new drug research and development. Pancreatic lipase (PL, also named triacylglycerol acyl hydrolase), a key enzyme responsible for the hydrolysis of 50%-70% dietary fats in the gastrointestinal system, which has been recognized as a crucial target for the prevention and treatment of obesity. PL inhibitors can reduce the decomposition and absorption of dietary fat in the digestive organs by decreasing the hydrolytic activity of this key enzyme, which can alleviate the symptoms of metabolic diseases such as obesity and hyperlipidemia. Although a potent PL inhibitor (orlistat) has been marketed, it may trigger gastrointestinal side effects after long-term use. Therefore, it is necessary to develop more new PL inhibitors with strong inhibition potency and safety. In recent years, a large number of studies have found that some Chinese herbal extracts and their constituents can regulate lipid metabolism and treat obesity via inhibiting PL. In this paper, the research progress in the field pancreatic lipase inhibitors, as well as the extracts of Chinese herbs and their constituents with pancreatic lipase inhibitory effects were summarized. Meanwhile, the PL inhibition activities and inhibitory mechanisms of herbal constitutes were also summarized systematically. In addition, the authors also highlight the challenges in this field and the future research directions. All information and knowledge presented in this review will be very helpful for the medicinal chemists to find more potent PL inhibitors from herbs or to develop next generation anti-obesity drugs, as well as helpful for the prevention and treatment of obesity and other related metabolic diseases using herba medicines or related products.
Traditional Chinese medicine (TCM) has made numerous contributions to the prosperity of China. However, the phytochemicals of TCM are complex, and there are significant differences in relative content. The material basis of TCM has restricted the modernization of TCM. Liquid chromatography-mass spectrometry (LCMS) combines the high separation performance of chromatography and the high sensitivity of mass spectrometry. It has been widely used in the analysis of natural medicines and can greatly promote the development of TCM. Many studies have focused on the comprehensive characterization of phytochemicals, building a strategy for the rapid, accurate and systematic analysis of the chemical components of TCM through the integration of different mass spectrometric techniques, and laying the foundation for quality control and rational utilization of TCM.
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