Latest ArticlesThis article reviews the secondary metabolites produced by marine microorganisms with anti-Pseudomonas aeruginosa activity in the past five years. The compounds are classified according to their structures, including macrolides, anthraquinones, peptides, alkaloids, terpenoids, and other kinds of structures. The chemical structure and antibacterial activity of these compounds are mainly introduced. This article provides a reference for further research and development of natural products from marine microorganisms with antibacterial activity.
Fingerprint refers to the chromatography, spectrum or other visual data that can identify the essential characteristics of certain substances or components with complex ingredients after proper processing and analysis. The analysis of effect components in biological samples is characterized by complex biological medium components, large differences in physical and chemical properties, complex and diverse metabolic reactions of effect components, and mainly trace amounts of prototypes and metabolites. Therefore, accurate and rapid determination of the effect components is of great significance. The advantages and disadvantages of each method in recent years are analyzed. The development trend of fingerprint technology in the analysis of effect components in biological samples is prospected in the future, so as to provide reference for the development and application of fingerprint technology in the field of biological sample detection.
This article focuses on the methods for determining vaccine potency, especially the feasibility and challenges of replacing traditional in vivo methods with in vitro methods, as well as related considerations. The in vivo method for determining vaccine potency has been used for a long time for vaccine quality control, but it has problems such as high variability, low experimental efficiency, and animal ethics issues. With the 3R principle and technological progress, in vitro methods have gradually become a trend to replace in vivo methods. In vitro testing methods have advantages in evaluating the consistency of vaccine production and monitoring changes during the production process, and can more effectively evaluate the stability and immune effects of vaccines. Although the mechanisms of in vitro and in vivo methods are different, and the quality control attributes of the two methods are not completely consistent, in vitro methods can still effectively replace in vivo potency assays, especially for quality control during the early stages of vaccine development. Common in vitro alternative methods include immunoassay, physicochemical analysis, and molecular biological assay. The selection of appropriate methods depends on the type of vaccine and its mechanism of action. In addition, the article emphasizes that the establishment of in vitro methods should be included in the vaccine development process as early as possible, and ensure its stability, reproducibility, and correlation with clinical efficacy. Although the promotion of in vitro alternative methods faces challenges, with technological progress, it is expected to further replace animal experiments in the future, improving the efficiency and ethicality of vaccine quality control.
Compared with normal cells, tumor cells exhibit unique metabolic characteristics. The therapeutic strategies formulated based on the energy metabolic features of tumors aim to block the energy and material supply of tumor cells at the source, remodel the immunosuppressive tumor microenvironment (TME), and create favorable conditions for immune cell infiltration and function. In recent years, Chinese herbal medicine-derived extracellular vesicles have attracted attention due to their unique metabolic regulatory capabilities and targeting properties. These extracellular vesicles can not only precisely deliver multi-component active molecules but also reprogram the metabolic processes in the tumor microenvironment, reverse immunosuppressive conditions, and thereby enhance antitumor immune responses. This review systematically summarizes the metabolic regulatory mechanisms of TCM-derived vesicles and their synergistic effects in immunotherapy, and looks forward to their clinical transformation potential and future research directions.
Tripterygium wilfordii Hook F (TWHF), specifically triptolide (TP), is an active compound derived from the plant with significant anti-rheumatoid arthritis (RA) effects. Studies show that TP exerts potent anti-inflammatory and antioxidant properties by inhibiting the expression of several inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. In terms of immune regulation, TP modulates the activity of immune cells like T cells and neutrophils, reducing inflammation and tissue damage. Additionally, TP can regulate multiple signaling pathways, including NF-κB, JAK/STAT, and MAPK, to suppress the proliferation and invasion of synovial cells in RA, thereby mitigating joint damage. With the advancement of nanotechnology, the development of TP-based nanomedicine has gained attention in recent years. Innovative nanocarriers, such as polymer nanoparticles, exosomes, and inorganic nanoparticle drug delivery systems, have significantly improved TP's bioavailability and targeting capabilities while reducing its toxicity. By modifying the surface of these nanomaterials, their ability to target and release TP at inflammation sites is enhanced, leading to more precise drug delivery. Moreover, nanomedicines extend TP's circulation time in the body and reduce early-stage toxicity, thus improving the therapeutic outcomes for RA. In conclusion, TP and its nanomedicine formulations show great promise in RA treatment. Future research should continue to explore their mechanisms and clinical applications, offering new perspectives for the treatment of rheumatoid arthritis.
During the decoction process of traditional Chinese medicine (TCM), not only do chemical bonds interact, but non-covalent interactions also occur. In recent years, studies have discovered the presence of aggregates connected by non-covalent bonds in TCM decoctions, collectively referred to as supramolecules of traditional Chinese medicine (STCM). This review summarizes the literature on STCM, discussing research methods, formation mechanisms, and research significance from four perspectives: individual components, single herbs, medicinal pairs and compound prescriptions. The aim is to provide a reference for future research on STCM. Due to the complexity and diversity of TCM components, the research on the formation mechanism of STCM in compound formulas, drug pairs and single herb decoction liquids is not perfect, which is also a key and difficult point in future STCM research. The perspective of self-assembled supramolecular chemistry provides a new idea for the study of the pharmacodynamic material basis of TCM, and pushes the research in the field of TCM to a new height.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown significant potential in cancer therapy due to its ability to selectively induce apoptosis in tumor cells while minimally affecting normal cells. Currently, developed TRAIL-based cancer therapies have demonstrated better therapeutic effects in preclinical trials. However, their clinical application has been limited by issues such as poor stability, insufficient targeting, short half-life in vivo, and low bioavailability. In recent years, nanocarriers, including liposomes, nanoparticles, and micelles, have been widely utilized in the field of drug delivery. Combining TRAIL with these nanocarriers can help overcome these limitations and enhance its antitumor efficacy. This review summarizes the latest research progress on the combination of TRAIL with liposomes, nanoparticles, and micelles in cancer treatment. It explores the mechanisms by which these nanocarriers improve the stability, targeting, and bioavailability of TRAIL, as well as the therapeutic advancements of this combined approach at both the animal and clinical levels. The aim is to provide valuable insights for the development and clinical application of TRAIL-based cancer therapies.
With the introduction of the concept of precision medicine, pharmaceutical treatment is shifting from 'one-size-fits-all' to personalization, and 3D printing, as an emerging formulation technology, can significantly enhance the complexity and flexibility of formulations, solve the many problems of the traditional process, and achieve personalized drug therapy. In recent years, with the rapid development of 3D printing technology, various 3D printing technologies have been used to develop oral solid dosage forms. Given the differences in the types and characteristics of 3D printing technologies, it is necessary to select appropriate printing materials according to the application characteristics of printing technology, and the choice of materials can significantly impact the personalized shaping and precise release of oral solid dosage forms. This paper lists the principles and characteristics of fused deposition molding technology, semi-solid extrusion technology, melt extrusion deposition technology, and binder jetting technology, which is suitable for the 3D printing of oral solid preparations. It explores the selection and application of printing materials for commonly used 3D printing technologies in detail to guide the choice of materials to prepare different principles of 3D printing of oral solid preparations.
Mechanistic modeling, which describes cellular metabolic behavior through mathematical equations, is an important theoretical tool for optimizing and predicting biological processes. In this study, a cell culture mechanistic model for biosimilar trastuzumab was constructed based on the Monod growth metabolism model. To address the high complexity of differential equation parameter fitting and the tendency to fall into local optima, particle swarm optimization (PSO), grey wolf optimization (GWO), and differential evolution (DE) algorithms were introduced for model parameter fitting. The results show that GWO outperforms the others in global search capability and fitting accuracy, demonstrating higher stability and adaptability in handling multi-parameter fitting problems. Furthermore, improvements were made to the position and velocity update methods of the GWO algorithm. The improved grey wolf optimization (IGWO) significantly enhanced the model's predictive ability, enabling accurate predictions of cell density, metabolite concentration, and antibody titer. This study provides important theoretical support for improving the production efficiency of biopharmaceuticals, reducing development costs, and optimizing cell culture processes.
With the widespread dissemination of the plasmid-mediated colistin resistance gene mcr-1, colistin resistance has spread globally, severely threatening the last line of defense in global anti-infective therapy. This study aimed to evaluate the resistance-reversing effects of linalool combined with colistin against mcr-1-positive Escherichia coli (E. coli) and to elucidate the underlying mechanisms, aiming to propose a therapeutic strategy to combat colistin resistance. The synergistic antibacterial effects in vitro were determined using the broth microdilution checkerboard method and time-kill curves, and biofilm assays. Further investigations elucidated the underlying mechanisms by assessing inner/outer membrane permeability, membrane potential (ΔΨ), dehydrogenase activity (DHA), proton gradient (ΔpH), ATP levels, and mcr-1 gene expression. Finally, we assessed the in vivo efficacy of linalool in combination with colistin against Galleria mellonella infection and mouse acute peritonitis models. Results demonstrated that linalool-colistin combination exhibited synergistic antibacterial effects against mcr-1-positive E. coli both in vitro and in vivo. Mechanistically, linalool directly damaged the bacterial outer membrane, reduced ΔΨ, and increased inner membrane permeability. Moreover, linalool inhibited DHA activity, disrupted ΔpH establishment, ultimately impairing ATP production. Additionally, linalool significantly downregulated the mcr-1 expression, suppressing lipid A modification in resistant strains. These effects collectively enhanced colistin penetration, triggering membrane disruption and energy metabolism collapse, ultimately achieving synergistic antibacterial efficacy. In vivo, combination therapy significantly improved survival rates in both infection models. In conclusion, linalool restores colistin susceptibility in mcr-1-positive E. coli through synergistic mechanisms, providing a promising therapeutic strategy against colistin resistance. All animal experimental procedures were reviewed and approved by the Animal Welfare and Ethics Committee of Xiangnan University (approval No.: 2023DWLL029).
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