Latest ArticlesA novel sort of nano-component was extricated and isolated from Descurainiae Semen Carbonisatum (DSC), and its hemostatic component was considered through pharmacological experiments. A muffle furnace was used to prepare DSC at 250℃, 300℃ and 350℃, and the DSC dialysate at each temperature was obtained by the extraction and separation method. Low-resolution transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM) were utilized to characterize the nano-components. Ultraviolet spectroscopy (UV-Vis), fluorescence spectroscopy (FL) and infrared spectroscopy (FTIR) were utilized to measure its optical characteristics and functional group information. The anti-hemorrhagic effects were evaluated by liver bleeding tests and the related hemostatic mechanisms of the obtained nano-components were further assessed by detecting blood coagulation and PLT quantity to discuss the hemostasis mechanism. The experiments complied with the Animal Ethics Committee of Beijing University of Chinese Medicine. TEM results showed that there was a novel type of nano-component in the DSC dialysate bag, which was named DSC nano-components (DSC-NCs). The experimental results of liver bleeding in mice showed that DSC-NCs prepared at 250℃, 300℃, and 350℃ could reduce the bleeding time of mice liver. Among them, DSC-NCs prepared at 350℃ had the best effect. In addition, DSC-NCs prepared at various temperatures can also reduce the prothrombin time (PT) value, increase the fibrinogen (FIB) value and the platelet (PLT) value to varying degrees. DSC-NCs have a certain hemostatic effect, which may be related to the activation of the exogenous coagulation system, the increase of FIB value and the increase of platelet content. This provides a new research direction for exploring the treatment of bleeding diseases, and provides a new perspective for the potential application of DSC-NCs in the medical field.
The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide-arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2±7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17±1.88)%, an encapsulation rate (5.85±0.72)%, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.
The key factors for producing the best quality Chinese herbal medicines are high-quality germplasm, suitable cultivation area and the proper processing methods for herbal raw materials. Gentiana crassicaulis in Gentiana (Sect. Cruciata), Gentianaceae is one of the original plants of the Chinese herb Qinjiao (Gentianae Macrophyllae Radix), and its type specimen was collected in Lijiang, Yunnan. There is a long planting history of the herb in this area. In this study a sampling plot was designated in these traditional planting areas. G. crassicaulis was planted and herbal raw materials were harvested from the plot. The raw materials were prepared locally and at a pharmaceutical factory in Shanghai using processing methods such as "sweating" or "no sweating", "slicing" or "no slicing" (whole root), and "stoving" or "no stoving" (air drying). The quality of all processed samples was evaluated. In addition, molecular markers were determined for identifying cultivated and wild samples from Lijiang, Yunnan. The results are as follows: ① Samples from the sampling plot and the field are taxonomically identified as Gentiana crassicaulis. ② A total of 270 sequences of trnC-GCA-petN, atpB-rbcL, psbN, ndhB-rps7 and ycf1 were obtained, and three genotypes were determined from the cultivated samples; the type Ⅲ was shared by both cultivated and wild plants. Based on the molecular markers, a DNA barcoding method to identify cultivated and wild samples of G. crassicaulis from Lijiang, Yunnan was established. ③ Total content of loganic acid and gentiopicroside in all samples was ≥ 2.5%, and above the Chinese Pharmacopoeia (2020) limit. ④ In HPLC fingerprinting, 9 common peaks were assigned and similarity between all samples was > 0.999; and ⑤ In a PCA score plot all slice samples were clustered, while whole root samples were scattered. Therefore, our studies could provide basic data for optimizing the processing method, producing best quality Gentianae Macrophyllae Radix, and evaluating the quality of different ecotype varieties and the multiple origin of herbal medicines.
Rhei Rhizoma is commonly used as a traditional Chinese medicine with multiple botanical origins. Different botanical sources may have different pharmacological activities. The germplasm resources of commercial Rhei Rhizoma were determined based on the chloroplast gene matK, and the anthraquinone and free anthraquinone content was determined by UPLC to analyze quality of commercial Rhei Rhizoma. Eighty-nine commercial Rhei Rhizoma samples were collected from 40 cities in 27 provinces. DNA was extracted and the matK gene was amplified by PCR. Results indicated that the collected samples were from the same botanical origin, Rheum palmatum, and 8 genotypes were identified, including Rp1, Rp2, Rp3, Rp4, Rp5, Rp6, Rp10 and Rp12. Rp4 and Rp6, cultivated in Gansu, Sichuan and Yunnan provinces were the main circulating genotypes, representing 40.45% and 37.08% of the total samples, respectively. Phylogenetic tree analysis showed that the eight genotypes were mainly divided into two branches, of which the main genotypes Rp4 and Rp6 were in one branch. Genetic distance analysis indicated that the genetic separation of the eight genotypes was between 0.001 and 0.010. UPLC analysis indicated that 93.26% of the samples met the Pharmacopoeia standards. There were significant differences in the content of total anthraquinone and free anthraquinone among the samples, in which the difference in free anthraquinone was 1.01% and the difference in total anthraquinone content was 3.79%, indicating that the quality of commercial Rhei Rhizoma samples varies considerably. There was no significant difference in the content of total anthraquinone and free anthraquinone in commercial Rhei Rhizoma among different collection provinces and genotypes. This study will help guide the circulation of Rhei Rhizoma in the market and provides valuable insights for molecular identification and quality analysis of other traditional Chinese medicines.
In this study, nrDNA ITS sequences of Lycium cultivars were sequenced and used to test the existence of incomplete concerted evolution and pseudogenes. Together with 44 ITS sequences retrieved from GenBank, the pattern of base substitutions, GC content, 5.8S conserved motifs, the minimum free energy of secondary structures, nucleotide diversity and phylogenetic relationship of the samples were analyzed. While 83 of the 144 sequences were identified as pseudogenes, the results suggested a high degree of polymorphism and putative pseudogenes in Lycium, suggesting an incomplete concerted evolution of the ITS region. ITS polymorphism and pseudogene of Lycium were systematically tested for the first time. This research provides a references for ITS sequence to be used in the study of Lycium germplasm resources and DNA barcode identification.
Hair roots induced by Agrobacterium rhizogene produce higher levels of secondary metabolites than non-induced plants, and the enhanced metabolic capacity is driven by the rol gene. We hypothesized that rol genes can be utilized to improve the biosynthesis of tropane alkaloids (TAs) in Atropa belladonna. In this study, the rolC gene from Agrobacterium rhizogene pRiA4 plasmid, driven by a CaMV35S promoter, was overexpressed in A. belladonna. The phenotypes, TAs content and transcriptional expression of key genes in TAs biosynthesis were analyzed in transgenic A. belladonna plants. Results show that transgenic A. belladonna exhibited a well-developed root system, male sterility, higher stamen column length than pistil, early flowering, internode shortening, smaller but more flowers, increased axillary buds and lateral buds, decreased apical dominance, and long and narrow leaves as compared to wild-type plants. Transgenic A. belladonna produced more TAs than wild-type plants, with the content of hyoscyamine, anisodamine and scopolamine reaching 2.58, 3.59 and 15.77-fold that of the control group, respectively. The gene expression of putrescine N-methyltransferase (PMT), tropinone reductase I (TRⅠ) and hyoscyamine 6-β-hydroxylase (H6H), key enzymes in TAs biosynthesis, were up-regulated compared with the control group. The above results indicate that the rolC gene enhances TAs biosynthesis in A. belladonna by up-regulating the expression of key enzymes in the TAs biosynthesis pathway, laying a foundation for genetic manipulation of A. belladonna to increase TAs content by increasing rolC gene expression.
Due to the complexity of tumor pathology, the demand for the combined use of multiple drugs in clinical treatment has become increasingly clear-cut. Multi-drug combination can act on multiple pathways and multiple targets simultaneously to exert synergistic effects. However, the current delivery strategy for multi-drug combination still needs to be optimized. Nano-drug delivery systems can carry drugs to overcome physiological and pathological barrier to target tumor tissues and cells, achieve the goal of continuous, controllable, and targeted delivery, and enhance the efficacy of anti-tumor synergism and detoxification. To meet the new requirements for smarter and more accurate antitumor multi-drug combinational therapy, the nano-drug delivery system has been well-designed to realize more functions. For instance, delivery of multiple drugs in accurate proportions and doses can make the multi-drug synergistic effect more precise; stimulus-responsive drug release can improve selectivity and reduce side effects; controlling the time-course relationship of multiple drugs can realize sequential drug combination effect. It has shown broad prospects in the field of tumor multidrug therapy and has become one of the new directions of research and development. This article reviews the recent developments in the application of tumor drug combination therapy strategies and their delivery systems, and analyzes the new requirements and challenges of multidrug combination for the development of nano-drug delivery systems.
Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.
Polydopamine (PDA) is a novel type of polymer synthesized inspired by adhesion proteins in mussels. It has been widely used in tumor-targeting drug delivery systems due to its natural advantages such as good biocompatibility, excellent photothermal conversion performance, adhesion, high chemical reactivity and multiple drug release response mechanisms. This review summarizes the applications of PDA-based tumor-targeting drug delivery in recent years, hoping to provide references for designing a more reasonable and effective PDA-based multifunctional collaborative tumor therapy platform.
At present, cancer is still one of the most serious threats to human health. Despite the wide application of multiple cancer therapies in clinical practice, the therapeutic effects of most cancers are still far from satisfactory. In recent years, the discovery of regulated cell death may be a good first step on the road to treat cancer. Ferroptosis is triggered by lipid peroxidation of unsaturated fatty acids in cell membrane catalyzed by iron ion. It has been widely concerned as an emerging target for cancer therapy. With the booming of biomedical nanotechnology, ferroptosis as an emerging therapeutic target has attracted extensive attention. Here, we review the advance on the intersection of ferroptosis and biomedical nanotechnology. First, the research background of ferroptosis and nano-preparation as well as the feasibility of ferroptosis-based nano-drug delivery systems (nano-DDS) for cancer treatment are presented and analyzed. Then, the strategies for inducing ferroptosis based on nano-DDS are summarized, mainly including: the promotion of Fenton reaction, the inhibition of glutathione peroxidase 4 (GPX-4) and the restriction of the cysteine-glutamate exchange transporter (system Xc-). Furthermore, the combination therapy strategies based on biomedical nanotechnology induced ferroptosis are also discussed. Finally, we shine the spotlight on the prospects and challenges of ferroptosis-based nanotherapeutics in clinical application.