Latest ArticlesFerroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.
The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.
It is a common understanding that turbidity and precipitation of traditional Chinese medicine are easy to occur in the process of decocting. At present, our research group found that the cause of "multi-phase of traditional Chinese medicine decoction" mainly came from the interaction between the effective components of traditional Chinese medicine, especially the interaction of acid and base components. For example, the Liquorice and Rhizoma chinensis was a supramolecular system formed by a large number of active components in the decoction (> 30%), and could stably exist in the decoction system. In this study, the supramolecular part was extracted, and the morphology of the supramolecular part was characterized by scanning electron microscopy and dynamic light scattering. It was observed that the supramolecular particles were uniform in size and regular in shape. The main components of supramolecular sites were identified by liquid mass spectrometry (LC-MSn). The results of UV and IR spectra showed that the chemical components of Liquorice and Rhizoma chinensis in the co-decocting process collided with each other, and weak bonds were formed between the functional groups of the molecules, which then induced the aggregation to form supramolecules. Thereafter, Through the diarrhea model of mice, sensory evaluation and antibacterial activity evaluation found that Liquorice and Rhizoma chinensis decocted together enhanced the antibacterial activity of Rhizoma, and compatibility "reconcile" Rhizoma "big bitter cold" property compared with single decoction group and interval administration group. All animal experiments were approved by the Animal Ethics Committee of Beijing University of Chinese Medicine, and the relevant regulations of Beijing University of Chinese Medicine on experimental animals were strictly followed. In this study, supramolecular chemistry method was used to preliminarily discuss the scientific connotation of "increasing efficiency and decreasing toxicity" of Liquorice and Rhizoma chinensis combined decoction from three perspectives of "property, efficacy and taste", and provide new ideas for the basic research of "reconcile" compatibility of Liquorice.
Two ent-kauranoids were isolated from the ethanol extraction of rhizomes of Canna generalis (Cannaceae), and were purified by various technologies, including silica gel and high performance liquid chromatography, and their structures were determined by modern spectroscopy techniques as (5R, 8S, 9S, 10R, 13R)-2-oxo-ent-kaur-15-en-17-oic acid (1) and (4R, 5S, 8S, 9S, 10S, 13R)-19-hydroxy-ent-kaur-15-en-17-oic acid (2). Compound 1 is a new ent-kauranoid, and compound 2 is obtained from rhizomes of Canna generalis for the first time.
Effective supplementation of probiotics can be beneficial to intestinal health, but in situ analysis of probiotics activity has rarely been reported. In this study, by coupling fluorescein 5-isothiocyanate (FITC) and 5(6)-carboxytetramethylrhodamine N-succinimidyl ester (5(6)-TAMRA-SE) with D-lysine, two fluorescent D-amino acids (FDAAs) probes were obtained: green probe (fluorescein-D-lysine, FDL) and red probe (TAMRA-D-lysine, TDL). Then, we tried to label the three kinds of probiotics, Lactobacillus acidophilus (LA), Lactobacillus casei (LC) and Veillonella atypica (VA) in vitro. FDAAs was applied to the labeling of intestinal flora in mice, and a method was established to investigate the oral survival rate of three commonly used probiotics. All animal experiments were approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine. The results show that the two synthetic FDAAs can be non-toxic and 100% for the in vitro labeling of the three probiotics. Known by FDAAs two-step labeling of oral probiotics, the high survival rate of LA was 92.30% ± 1.67%. The survival rates of VA and LC are similar, 84.13% ± 4.06% and 82.27% ± 2.43%, respectively. This study can quickly compare the changes of colonization survival rate of different probiotics in vivo, provide theoretical support for the in situ colonization activity of probiotics in the intestine, and guide the rational drug use of clinical probiotics.
The joint application of traditional Chinese medicine injection containing chlorogenic acid (CA) and cefotaxime sodium (CS) is sometimes appeared in clinical practice, but the scientific basis of drug molecular compatibility is still weak. This study proposes a sequential analysis strategy based on isothermal titration calorimetry (ITC), cold-spray ionization mass spectrometry (CSI-MS) and antibacterial activity test to evaluate the molecular interactions between CA and CS. The results of ITC experiments showed that the Gibbs free energy ΔG < 0 and it was driven by enthalpy change when CA titrated CS, suggesting CA could spontaneously chemically react with CS. Subsequently, the parent ions (m/z 808.143 5) of binding molecular of CA and CS was detected by CSI-MS, indicating CA could chemically bond with CS. Furtherly, the antibacterial experiments found the antibacterial ability of CS against Klebsiella pneumonia was significantly reduced (P < 0.01) by CA in mixed solution. Finally, molecular docking technology showed CA and CS have a common target of penicillin binding protein 3 (PBP3), suggesting that the phenomenon of CA reduced the antibacterial ability of CS may be related to the competitive binding of two components with PBP3. Our studies have shown that CA could spontaneously chemically bond to CS and reduced its antibacterial ability, providing scientific data for molecular interaction evaluation of CA and CS.
Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.
Two new labdane diterpenoids were isolated from 95% ethanol extract of the leaves of Callicarpa formosana Rolfe by using silica gel column, MCI column, ODS column and HPLC. Their structures were elucidated by HR-ESI-MS, NMR and ECD spectral data. All of them are new compounds, named 13E-6β-hydroxylabda-8(17), 13-dien-15-oic acid (1) and 13E-7α-hydroxylabda-8(17), 13-dien-15-oic acid (2). Compounds 1 and 2 were tested for antioxidant activity, and none of them had obvious activity.
Hyaluronic acid is widely used in biomaterials, cosmetics, clinical medicine and other fields due to its good biocompatibility, degradability, hydrophilicity, tumor targeting, viscosity and other characteristics. Pharmacodynamic activities of natural small molecular products which derived from traditional Chinese medicine (TCM) are significant, but their low solubility and poor targeting limit the clinical application. Based on supramolecular properties of hyaluronic acid, in this review, numerous studies were reviewed on the improvement of solubility, bioavailability, targeting and suitable dosage forms of small molecular compounds in TCM by domestic and foreign scholars using hyaluronic acid as carrier. It provides new ideas and inspirations for exploring the potential application value of small molecule compounds in TCM and even for the research and development of new drugs.
Solid dispersion, a dispersion system in which drug molecules are highly dispersed in carrier materials, has been commonly used to improve the solubility and dissolution rate of poorly soluble drugs. The miscibility between drug and carrier is crucial to improve the dissolution performance and stability of solid dispersion. Therefore, the selection of carrier types and the optimization of drug loading are very important. In the current study, the solubility parameter method and Flory-Huggins theory were used to predict the miscibility between olaparib (OLP) and different carriers (VA64, Soluplus, Plasdone S630 and Kollidon K29/32). Besides, the carrier material with good miscibility was experimentally screened by differential scanning calorimetry (DSC). The optimum of drug-carrier ratio was further performed based on the miscibility phase diagram of drug and carrier. Theoretical calculation and experimental evaluation showed that the miscibility of OLP and VA64 was the best, and the drug loading of 30% could meet the requirements of large drug loading and physical stability. Polarizing light microscope, X-ray powder diffraction, DSC and laser confocal Raman spectroscopy exhibited that OLP was amorphous form in the solid dispersion system. Powder dissolution test demonstrated that the solid dispersion showed significantly enhanced dissolution rate in comparison to crystalline OLP. In this study, theoretical calculation and experimental evaluation were used to screen the types of carriers and optimize the drug loading, which provides an efficient strategy for the selection of carrier and the amount used in solid dispersion.