Angiogenesis is the formation of new capillaries from pre-existing vasculature, which plays a critical role in several diseases. Under the normal physiological conditions, only about 0.5% of endothelial cells (ECs) undergo mitosis, while the most ECs are in a resting state. Angiogenesis is a dynamic process in which ECs shift from resting to activated state, including three basic steps:① excessive vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), platelet-derived endothelial growth factor (PDGF) and other pro-angiogenic factors secreted by ECs can promote the germination of ECs in the original blood vessels; ② the sprouts are continuously elongated through the proliferation of ECs and the degradation and migration of basement membrane. At this time, the ECs present two phenotypes with filamentous feet and strong proliferation ability; ③ the buds are continuously elongated to form a tubular structure and connect with adjacent blood vessels, and the junction is wrapped by wall cells and basement membrane to form new blood vessels. Nowadays, angiogenesis has become a target for clinical treatment of multifarious diseases. On one hand, anti-angiogenesis is used to treat various diseases with excessive angiogenesis, such as cancer, atherosclerosis, and diabetic retinopathy, etc. On the other hand, the diseases caused by insufficient angiogenesis, including myocardial infarction, myocardial ischemia/reperfusion injury, stroke, wound long-term healing and other ischemic diseases can be improved by pro-angiogenesis therapy. Large numbers of researches have shown that many active ingredients of traditional Chinese medicine can effectively treat the previously mentioned diseases by regulating angiogenesis in different ways. Therefore, the anti-and pro-angiogenesis effects of some active ingredients derived from traditional Chinese medicine and their mechanism were summarized in this manuscript, arming to provide theoretical basis for the development of new drugs for the treatment of angiogenesis-related diseases.

Snake bite is a common acute and severe disease in tropical and subtropical regions, and its public health importance has been largely neglected. Snake venom is a complex mixture of active proteins, polypeptides, and other toxins. Many of these components can target multiple ion channels, cell receptors, and membrane transporters. Compared with traditional small molecule drugs, the proteins and polypeptides from snake venom have stronger specificity and affinity to targets and are especially suitable for novel drug design. The current studies show that snake venom and its components have great potential for development as leading compounds of new drugs. In this paper, the recent advances in main components, toxic effects, and detoxification strategies of snake venom, as well as its pharmacological activities and medical application are reviewed. The aim is to provide reference for clinical diagnosis and treatment of snake bite and development of new drugs based on snake venom.

In recent years the role of sphingosine kinase 2 (SphK2), a key enzyme in the sphingolipid pathway, in the process of tumorigenesis has gradually been elucidated. Recent research has shown that SphK2 inhibitors can be used as anticancer drugs alone or in combination with existing drugs to increase the therapeutic sensitivity of drug-resistant tumors. Among them, one selective SphK2 inhibitor, ABC294640, shows excellent oral bioavailability and biodistribution in vivo and has now entered Phase Ⅱ clinical research. Therefore, developing innovative drugs based on SphK2 is of great interest. Herein, we discuss progress in understanding the role of SphK2 in tumorigenesis and review the recent development of inhibitors of SphK2.

To identify an effective structural modification strategy for improving the antitumor activity of fluoroquinolones, sixteen new 1-cyclopropyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-arylidene-2, 3-dihydroquinolin-4(1H)-ones compounds (4a-4p), were designed and synthesized by a condensation reaction of dihydroquinolin-4-one (3) and aromatic aldehydes, based on the structure of ciprofloxacin (1). Their structures were characterized by elemental analysis and spectral data, and anti-cell proliferative activities against Hep-3B, Capan-1 and HL60 cell lines were measured by an MTT assay. Preliminary pharmacological results indicated that the synthesized target compounds had greater potency than ciprofloxacin (1). SAR revealed that the halophenyl compounds such as fluorophenyl (4h, 4i), chlorophenyl (4j, 4k) or bromophenyl compounds (4l, 4m) and aromatic heterocyclic compounds such as furanly (4n) or pyridyl compounds (4o, 4p) demonstrated better activity than the control compounds, and the IC₅₀ values of the chlorophenyl compounds 4j and 4k against Capan-1 cell growth were comparable to that of doxorubicin. Thus, a 3-arylidene as an isostere of the C-3 carboxylic acid group appears to be beneficial in improving the antitumor activity of fluoroquinolone. Furthermore, an α, β-unsaturated ketone fragment used as a potential bioisostere of C-3 carboxylic acid group may warrant further study.

Gut microbiota dysbiosis is closely related to a variety of host diseases. Recently, targeting the metabolic pathways of gut microbiota for the prevention and treatment of host diseases has become a frontier strategy and research hotspot. Inflammatory bowel disease (IBD) is a group of chronic progressive intestinal inflammatory diseases of unknown etiology. The relationship between IBD and gut microbiota disorders and bacterial respiratory/energy metabolism has been confirmed in recent research. This article will introduce the relationship among them, and propose a new treatment strategy to alleviate host gut inflammation by regulating gut microbiota respiration and energy metabolism based on the latest research progress. In the progression of IBD, the gut microbiota homeostasis is disturbed. The main reasons include two aspects:on the one hand, when the intestinal inflammation of the host occurs, with increasing of oxygen concentration in the intestinal cavity, facultative anaerobic bacteria, especially Enterobacteriaceae bacteria would proliferate abnormally; while the growth of absolute anaerobic bacteria such as Firmicutes is inhibited. On the other hand, intestinal inflammation by-products also support the expansion of facultative anaerobic bacteria, which ultimately exacerbates the imbalance of gut microbiota. Dysregulated intestinal flora will further disturb intestinal immune homeostasis and exacerbate intestinal inflammation. The latest research proposed the possibility that IBD can be alleviated by interfering with the respiration of bacteria, inhibiting the abnormal proliferation of bacteria, or increasing the level of "beneficial" metabolites of gut microbiota. The above studies suggest that alleviating host intestinal inflammation can be explored by focusing on the metabolic pathways of gut microbiota and regulating the intestinal bacterial respiration and energy metabolism, which is of great significance for the clinical treatment of IBD and the research of innovative drugs.

Breast cancer is the most common malignant tumor in women worldwide. In breast cancer tumor tissues, a variety of targets related to the occurrence and development of breast cancer have been observed, and many drugs have been used in clinical applications for these targets. However, most of these drugs are small molecule inhibitors. With the long-term use of these drugs, acquired drug resistance often occurs in breast cancer patients. To overcome the drug resistance, the development of more efficient drugs is highly desirable in the treatment of breast cancer. Proteolysis targeting chimera (PROTAC) technology is a new kind of targeted protein degradation technology, which has shown broad prospect of applications in the field of drug development. The use of PROTAC technology to target the degradation of relevant targets in breast cancer has become a feasible strategy for breast cancer treatment.

Glucose-6-phosphate dehydrogenase, a key enzyme in the pentose phosphate pathway, plays an important role in plant resistance. In this study, three full length cDNAs of G6PDH genes, namely AsG6PDH1, AsG6PDH2 and AsG6PDH3 were cloned from Aquilaria sinensis for the first time. The open reading frames (ORF) of AsG6PDH1, AsG6PDH2 and AsG6PDH3 were 1 809, 1 767 and 1 548 bp, respectively, encoding proteins of 602, 588 and 516 amino acid residues, respectively, with predicted molecular masses of 68.02, 67.02, 59.35 kDa, respectively. The three AsG6PDHs proteins shared high sequence identity with the G6PDH proteins of various plants, and possessed three conserved sequences found in G6PDH proteins. The phylogenic analysis showed that AsG6PDH1 and AsG6PDH2 were grouped in the plastidic cluster, while AsG6PDH3 was classified into the cytosolic cluster. Expression analysis indicated that AsG6PDH1 and AsG6PDH2 were primarily observed in root, while AsG6PDH3 was primarily observed in stem. The expression of AsG6PDH1, AsG6PDH2 and AsG6PDH3 was induced by salt, drought, low temperature and CdCl₂ treatments, while the content of AsG6PDH1 and AsG6PDH2 was most significantly increased by drought stress, and the transcript level of AsG6PDH3 was most significantly induced by metal stress. Furthermore, G6PDH activity was stimulated under salt, drought, low temperature and CdCl₂ treatments, and G6PDH activity was remarkably increased under drought stress. These results provide valuable insights into the role of AsG6PDHs in plant defense and the mechanism of agarwood formation.

Ursodeoxycholic acid (UDCA) is an essential drug for the treatment of cholestatic liver diseases. As the most important representative of endogenous drugs, the metabolism and disposition of UDCA in human is characterized by both host-gut microbial co-metabolism and hepato-billilary-intestinal circulation. These distinct metabolic and pharmacokinetic features have brought great challenges into the bioequivalence (BE) evaluation of UDCA generic formulations. These challenges include not only biopharmaceutical problems derived from the unique physiochemical properties of amphiphilic molecules and the large single dose, but also the drug metabolism and pharmacokinetic problems associated with endogenous metabolism, long terminal half-life, high inter-and intra-individual variations, as well as accurate determination of UDCA and its metabolites. This review summarized academic and industrial literatures about the clinical pharmacokinetics and endogenous metabolism of UDCA. Current guidelines and technical challenges of UDCA BE studies were extensively discussed. Knowledge summarized in this review is expected to provide valuable reference for the development of UDCA generic formulations.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and cartilage destruction. An imbalance in macrophage polarization is closely related to the occurrence and development of RA, including a central role for M1 macrophages in promoting inflammation and bone destruction in the cytokine network environment of RA. It is a remarkable fact that the abnormal immune-microenvironment in RA patients promotes the metabolic reprogramming of macrophages, which disrupts the dynamic balance of M1/M2 by regulating the polarization of macrophages, leading to a persistent tissue inflammation. Using drugs to inhibit M1 macrophage polarization or induce M2 macrophage polarization is expected to be an ideal strategy for drug development for RA treatment. This review summarizes the effects of metabolic reprogramming of macrophages on polarization phenotype and the metabolism-related signaling pathways in the RA microenvironment, and provides references for the development of RA drugs that can target macrophage metabolism.

Animal derived traditional Chinese medicines (ATCMs) are an important part of traditional Chinese medicine (TCM). The lack of proper ideas and strategies made it not systematic and perfect enough on investigating bioactive components and quality evaluation of ATCMs, which restrict many aspects of ATCMs investigation including clinical applications, pharmaceutical technologies, and quality control. Therefore, based on our previous investigations of animal horn and animal derived gelatin TCMs, and the research progress at home and abroad, ideas and strategies for investigating the correlations between proteins/peptides and their bioactivities in animal horn and animal gelatin derived TCMs based on integrated "proteomics/peptidomics-modifications" methods was proposed. Firstly, proteomics and peptidomics analysis can be used to study proteins and peptides in ATCMs. Secondly, modification analysis can be used to reveal those chemical modifications on proteins and peptides of ATCMs. Thirdly, the correlations between components, modifications and traditional bioactivities can be systemic discussed. Based on the present study, hopefully, enough evidences and reference can be provided to resolve the issues in ATCMs investigations on modernization and bioactive material basis.