Latest ArticlesMetal-organic frameworks (MOFs) are porous crystalline polymers constructed from the coordination reaction between organic ligands and metal ions. Due to their advantages:adjustable periodic pore structure, large specific surface area and easy functional modification, etc., MOFs have been widely used in the fields of gas storage/separation, catalysis, sensing, biological imaging and drug delivery. In recent years, MOFs have shown great potential in disease diagnosis and treatment. This review summarizes the application of MOFs in the fields of bio-sensing, cell imaging, in vivo imaging, drug delivery, etc., discusses the problems and corresponding solutions in the application of MOFs for biomedicine. We hope this review can provide reference for the designing new methods for disease diagnosis and treatment.
Inspired by the coordination effects between imidazole and metal ions in hemoglobin, biomimetic nanoparticles were constructed for photodynamic tumor therapy. The photosensitizer of protoporphyrin IX (PpIX) was modified with histidine, which could be self-assembled with Zn2+ to obtain the biomimetic nanoparticles (NPs). Under the conditions of high glutathione and low pH, the biomimetic nanoparticles could be degraded and released for enhanced photodynamic tumor therapy. The structures of NPs were characterized by dynamic light scattering (DLS), UV-visible spectrophotometer (UV-Vis), fluorescence microscope and transmission electron microscope (TEM). The reactive oxygen species (ROS) production ability of NPs was measured by singlet oxygen sensor green (SOSG) test kit. Mouse breast cancer cell lines (4T1 cells) were employed to investigate the subcellular organelle distribution and cytotoxicity of NPs. These results confirmed that NPs possessed a good dispersibility and stability with a uniform structure and particle size at 165 nm. Moreover, MTT assay and live/dead cell staining assay demonstrated that NPs could inhibit the proliferation of 4T1 cells and exhibit a good biocompatability. This research would promote the construction of intelligent biomedicine for tumor precision therapy.
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.
Exosomes are disk-shaped vesicles with a diameter of 40-100 nm, which are composed of natural lipid bilayers. Most cells can produce exosomes, which play an important role in physiological and pathological processes, affecting signal pathways, intercellular communication, tumor progression and molecular metastasis. Exosomes are characterized by low immunogenicity, good natural stability, long half-life, high delivery efficiency, and the ability to cross the blood-brain barrier, which can be used as a good carrier for drug delivery. This review focuses on the research progress of exosomes as drug delivery systems in the treatment of brain diseases, such as central nervous system degenerative diseases, brain tumors and cerebrovascular diseases and so on.
Cardiac glycoside is a class of steroidal glycosides with significant physiological activities to the heart. Several drugs had been approved for the treatment of heart failure and atrial fibrillation. In recent studies, the researchers have found that cardiac glycoside can selectively inhibit the proliferation of human tumor cells and has potent antitumor efficacy. Unfortunately, the poor solubility and severe adverse effects of cardiac glycoside hindered further clinical application in the field of anticancer. It is an effective strategy to solve the "drug-like" problem of cardiac glycoside by changing the pharmacokinetics and distribution in vivo and reducing the dosage and side effects by virtue of modern preparations technology and treatment scheme. In this review, a brief introduction of the developmental course and mechanism of cardiac glycosides in anticancer field was made, and recent research progress of cardiac glycosides preparations were summarized and discussed. Finally, the further research direction was prospected.
In recent years, the incidence and mortality of invasive fungal infections has increased. It is highly desirable to develop novel antifungal agents with new modes of action. Targeting virulence factors represents a new strategy for antifungal drug discovery. Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging antifungal target. However, discovery of small-molecule SAP2 inhibitors remains a significant challenge. Based on the structure-activity relationship of our previously identified triazine small-molecule SAP2 inhibitor, we were able to identify two potent inhibitors, 8a and 8c, which showed excellent in vivo antifungal activity for the treatment of C. albicans infection. Moreover, compounds 8a and 8b effectively inhibited fungal biofilm. Taken together, triazine SAP2 inhibitors represent promising lead compounds for the discovery of novel antifungal agents.
This research investigated the mechanism by which bupivacaine inhibits glutamate-induced intracellular free Ca2+ increases in primary cultured hippocampal astrocytes. Immunofluorescence was used to demonstrate the expression of metabotropic glutamate receptor (mGluR5 receptor) on neurons and astrocytes. Calcium imaging was used to measure the alteration of intracellular free Ca2+ ([Ca2+]i) in primary cultured rat hippocampal neurons and astrocytes. The animal experiments were approved by the Animal Experiments Ethical Committee of Hebei Medical University. The results showed that mGluR5 receptor was abundantly expressed in the primary cultured rat neurons and astrocytes. Bupivacaine (300 μmol·L-1) significantly inhibited 1 mmol·L-1 glutamate-induced[Ca2+]i increase in astrocytes (P < 0.01). 2-Methyl-6-(2-phenylethynyl)-pyridine (MPEP) (10 μmol·L-1) completely abolished the increase of[Ca2+]i induced by 1 mmol·L-1 glutamate in the astrocytes (P < 0.01), while the inhibitory effect on neurons was only 10%-20%. Bupivacaine (300 μmol·L-1) completely inhibited the[Ca2+]i increase induced by mGluR5 receptor agonists (RS)-3, 5-dihydroxyphenylglycine (DHPG) (50 μmol·L-1) and (RS)-2-chloro-5-hydroxyphenylglycine sodium salt (CHPG) (1 mmol·L-1) in astrocytes (P < 0.01). In addition, bupivacaine inhibited the CHPG-induced[Ca2+]i increase in a dose-dependent manner in astrocytes with an IC50 of 100 μmol·L-1. The results from this study indicate that bupivacaine inhibits glutamate-induced[Ca2+]i elevation by acting on the mGluR5 receptor in primary cultured hippocampal astrocytes.
Diabetes is characterized by hyperglycemia, resulting from insulin deficiency or resistance, or both. Insulin plays an irreplaceable role in the treatment of diabetes. Subcutaneous injection is the main route of insulin administration, but usually leads to poor compliance and many side effects. Oral insulin is safer and more convenient, which has always been the Holy Grail for people to explore. After oral administration, insulin is absorbed into the hepatic portal vein and transported to the liver, which can activate the normal physiological functions and reduce the risk of hypoglycemia, insulin resistance, and improve patient compliance. However, the gastrointestinal tract has multiple absorption barriers such as chemical barrier, enzyme barrier, and permeation barrier. Due to the physical and chemical properties of insulin, it is difficult to achieve desired oral bioavailability. This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials, including structural modification, enzyme inhibitors, absorption enhancers, various nanoparticles, liposomes, microspheres, and even microorganisms. Some clinical researches on oral insulin are also introduced.
Zedoary turmeric oil dry powder inhalers (ZDPIs) and curcumol dry powder inhalers (CDPIs) were prepared and intratracheally (i.t.) administered to the rats that suffered from acute lung injury (ALI) induced by lipopolysaccharide (LPS), and their therapeutic efficiencies were compared. Zedoary turmeric oil nanoemulsions and curcumol nanoemulsions were separately prepared and ZDPIs and CDPIs were obtained after the emulsions were added with 5% mannitol and lyophilized. ZDPIs and CDPIs are loose white powders with the aerodynamic diameters (Da) of 3.02 and 2.67 µm, respectively. Both ZDPIs and CDPIs were suitable for pulmonary delivery. Animal experiments were approved by the Ethics Committee of Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations. ALI rat models were established by i.t. administration of 0.2 mL of 5 mg·mL-1 LPS solution and ZDPIs (with zedoary turmeric oil 0.5 mg) or CDPIs (with curcumol 0.5 mg) were i.t. administered. Both of them remarkably alleviated bleeding of injured lung tissues, and great reduced the levels of inflammatory factors tumor necrosis factor-α, interleukin-6, total proteins in the lung tissues (P < 0.001). They showed similar high effect against ALI. The non-curcumol components in zedoary turmeric oils could also have anti-inflammatory effect. ZDPIs and CDPIs are promising medications for the treatment of ALI and this comparative study is a paradigm of the research on active ingredients and effective compounds in natural products.
The quality of the same herbal medicines in different daodi-origins in China is significantly different. Our research team previously found that using protocatechuic acid as a chemical marker can divide the Cynomorium songaricum into outside-the Great Wall (Inner Mongolia) and inside-the Great Wall (Gansu). However, the ecological mechanism that causes the quality variation of C. songaricum is unclear. Based on the microbiome-ecological strategy, 16s amplicon sequencing was performed on rhizosphere soils of C. songaricum in two origins (Inner Mongolia and Gansu), and the composition of soil microbial communities was analyzed. Tax4Fun was used to predict the metabolic function of soil microbial communities. Correlation analysis by combing with the abundance of key microbial community and ecological climate factors was performed. Microbiome sequencing results revealed that the diversity of soil microbial communities in Inner Mongolia was significantly higher than that in Gansu. Five core microbiomes (Arthrobacter, Streptomyces, Bacillus, etc.) and six specific biomarkers of soil microbial communities (Microbulbifer, Methyloceanibacter, Cynomorium_coccineum, etc.) which could be distinguished from two origins were identified. For the first time, metabolic function prediction showed the metabolic function profile of soil microbiome of C. songaricum in two origins. Redundancy analysis and correlation analysis results showed that the annual sunshine hours was the main ecological factor affecting the composition of the soil microbial community of C. songaricum, and it was extremely significantly negatively related to Streptomyces and Bacillus. This article provides a new idea for explaining the formation mechanism of quality variation in the daodi-origins of C. songaricum, and also provides a scientific basis for theoretical research on the quality ecology of herbal medicines.