Polydatin (PD) is a natural active crystalline compound extracted from the roots and stems of Polygonum cuspidatum, and is a natural precursor of resveratrol. This study aims to investigate the therapeutic effects of PD on monosodium urate (MSU)-induced gouty arthritis in mice and its potential mechanisms. The animal experiment has been approved by the Ethics Committee of Nanjing University (approval number: 2407002). A gouty arthritis model was established by injecting 20 μL of MSU (25 mg·mL^-1) suspension into the mouse plantar. The effect of PD on pathological changes in the mouse plantar was evaluated. The treatment group received daily intraperitoneal injections of different doses of PD (low dose: 5 mg·kg^-1, medium dose: 10 mg·kg^-1, high dose: 20 mg·kg^-1) for 3 days before model induction. The thickness of the mouse plantar was measured and photographed at 3, 6, 9, 12, and 24 h after MSU suspension injection. Histopathological damage to the plantar tissue was observed using hematoxylin-eosin (H&E) staining. Immunohistochemistry and immunofluorescence were used to detect the expression of NLRP3 and CASP1 p20 to assess NLRP3 inflammasome activation in the plantar tissue. At the cellular level, lipopolysaccharide (LPS) combined with adenosine triphosphate (ATP)/MSU/nigericin was used to construct a cellular activation model of the NLRP3 inflammasome. ELISA was used to detect the effect of PD on interleukin-1β (IL-1β) secretion after NLRP3 inflammasome activation in macrophages. Flow cytometry was employed to measure CASP1 p20 activation in macrophages. Immunofluorescence was used to examine NLRP3 inflammasome assembly in macrophages. The results of the study indicate that, compared to the model group, the PD-treated group exhibited a significant reduction in the swelling of the mouse plantar. H&E staining showed a notable reduction in tissue damage in the mouse plantar, suggesting that PD has a therapeutic effect on plantar damage in mice. Immunohistochemistry and immunofluorescence results revealed a significant decrease in the expression of CASP1 p20 and NLRP3, indicating that PD significantly inhibits the activation of the NLRP3 inflammasome, thereby attenuating the local inflammatory response in the mouse plantar. At the cellular level, PD treatment significantly reduced the secretion of IL-1β and activation of CASP1 p20, both of which are mediated by NLRP3 inflammasome activation. Furthermore, NLRP3 inflammasome assembly was inhibited. In summary, PD exerts its anti-inflammatory effect by suppressing the assembly and activation of the NLRP3 inflammasome, reducing the production and release of the pro-inflammatory cytokine IL-1β, thereby alleviating joint damage in mouse gouty arthritis. This provides a novel strategy for the treatment of gout.

Tissue factor (TF), a transmembrane glycoprotein expressed in normal tissues, has a variety of physiological functions in embryonic development, hemostasis and non hemostasis pathways. Studies have found that TF is overexpressed in a variety of tumor tissues and promotes tumor progression. Kaplan Meier (K-M) survival analysis showed that high expression of TF gene was associated with poor prognosis in renal and pancreatic cancer. Therefore, TF has received extensive attention as a target of tumor immunotherapy, and a number of antibody-drug conjugates (ADC) drugs have entered the clinical research stage. In this paper, the gene structure, expression, biological function and the correlation with tumor of TF were systematically elaborated, and the direction of drug design for the new generation of TF-ADC was proposed, in order to provide theoretical support and development direction for the drug research and development of this target.

Polygonatum Mill. (Asparagaceae) is a pharmaceutically important genus with many species are of significant medicinal value. Taxonomy and interspecific identification of Polygonatum species have long been controversial due to their considerable morphological variation, wide geographic distribution, complex speciation processes, and lacking of high-resolution molecular markers. To evaluate species discrimination power of 14 plastid divergence hotspot regions (candidate sequences) and their combinations in Polygonatum, a total of 166 individuals from 32 populations representing 15 medicinal Polygonatum species distributed in China were sampled for study. The interspecific and intraspecific genetic variation of each sequence and sequence combination were estimated, and tree-based and pairwise genetic distance (PWG-distance) methods were applied. The results indicated that except for trnT-trnL, the designed primers for all the other 13 candidate sequences showed good universality. Varying degrees of overlaps were detected between intraspecific and interspecific genetic distances in each of the 14 single candidate sequences and their combinations. Nonetheless, overlaps in the combined sequences were significantly lower than those in single sequences. Species resolution of the 14 single sequences were 6.67%-40% and 20%-60% based on tree-based and PWG-distance methods, separately. The combined sequences possessed higher species-resolving power with 40%-73.33% by tree-based method and 46.67%-73.33% by PWG-distance method, accordingly. Among them, the combined sequences C0 and C1 (in both tree-based and PWG-distance methods), C2 and C3 (in tree-based method), and C25 (in PWG-distance method) all showed the best resolution degree of 73.33%, indicating that combination of sequences could effectively improve species discrimination power. In addition, sequences psaJ-rpl33, rps16-trnQ, trnF-ndhJ, trnT-trnL, trnK-matK and atpF all exhibited relatively higher species-resolving degree, which could be used as specific molecular markers for the identification of medicinal Polygonatum species, and we propose the combination of psaJ-rpl33+rps16-trnQ+trnF-ndhJ+trnK-matK+atpF as the most ideal high-resolution molecular marker for discriminating the medicinal Polygonatum. This study will provide a basis for conservation and utilization of germplasm resources and accurate identification of medicinal Polygonatum, as well as standardizing the market for Polygonati Rhizoma.

Fusobacterium nucleatum (Fn) is closely associated with the occurrence and progression of colorectal cancer (CRC). The development of specific antibacterial agents targeting Fn is crucial for the prevention and treatment of CRC. Based on the preliminary phenotypic screening results from our research group, dimetridazole was successfully identified as a hit compound with antibacterial activity against Fn. In this preliminary structural optimization study, we designed and synthesized seven novel nitroimidazole derivatives comprising three structural types, followed by antimicrobial evaluation of all target compounds. Among them, compound CL6 exhibited excellent antibacterial activity against Fn (MIC = 0.5 μg·mL^-1) and demonstrated good selectivity towards intestinal bacteria and normal cells. Compound CL6 significantly inhibited the migration of CRC cells (HCT116) induced by Fn preliminary mechanistic studies suggest that compound CL6 disrupts the integrity of the Fn bacterial biofilm and cell wall, providing a promising lead compound for the development of novel anti-Fn drugs.

Human and animal health will be seriously harmed by myocardial infarction, the diagnostic speed and the therapeutic effect of this disease need to be improved urgently. As the natural carrier for delivering cell information, some microRNAs (miRNAs) found in exosomes can reflect and act on the pathological changes caused by myocardial infarction for effective diagnosis and treatment. The feasibility of exosomal miRNAs (e.g. miR-4516, miR-203, and miR-1915-3p) from different sources as diagnostic agents for myocardial infarction, as well as the research progresses in relief of cell death via apoptosis (e.g. miR-21a-5p, miR-30e, and miR-210), autophagy (e.g. miR-125b-5p, miR-301, and miR-143-3p), pyroptosis (e.g. miR-182-5p, miR-133a, and miR-100-5p), and ferroptosis (e.g. miR-26b-5p and miR-23a-3p), promotion of forming new blood vessels (e.g. miR-29b-3p, miR-210-3p, and miR-494-3p), and inhibition of inflammatory response (e.g. miR-25-3p, miR-182-5p, and miR-671) for intervention therapy of myocardial infarction were reviewed here to provide new strategies for the diagnosis and treatment of myocardial infarction.

The genus Gynostemma, with abundant plant resources, is widely distributed in China. Gynostemma plants have gathered widespread attention both domestically and internationally due to their abundant contents of diverse dammarane triterpenoid saponins and various promising pharmacological activities. At present, the studies on the chemical constituents and pharmacological activities of Gynostemma plants mainly focus on G. pentaphyllum (Thunb.) Makino and G. longipes C. Y. Wu ex C. Y. Wu & S. K. Chen, with less attention given to other species within genus. In this study, the chemical constituents of G. burmanicum King ex Chakrav were systematically identified by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UHPLC-Q-TOF-MS). Firstly, the LC-MS analysis of G. burmanicum from different sources was carried out to evaluate the consistency. According to the mass spectrometry fragmentation pattern of dammarane triterpenoid saponins from Gynostemma, the fragmentation characteristics of malonylated and acetylated saponins, combined with the self-built database and online database such as ChemSipder, SciFinder, PubChem, the chemical components of G. burmanicum were identified. The similarities and differences in the components between G. burmanicum and G. longipes were further assessed by comparing their base peak chromatogram. The experimental results indicated a good consistency in the composition of G. burmanicum samples from different sources. A total of 47 chemical components were identified from G. burmanicum, including 12 flavonoids and 35 triterpenoid saponins, among which 6 were new compounds. Saponins in G. burmanicum generally exhibited malonylation and acetylation, appearing after the corresponding prototypical saponins on a reversed phase chromatography. The base peak ion (BPI) chromatograms showed that the saponins of G. burmanicum were highly consistent with those of G. longipes, with comparable contents of the main components gypenoside XLIX and gypenoside A and their malonylated derivatives. In summary, this study comprehensively clarified the chemical composition and characteristics of G. burmanicum, which provided an experimental basis for the development and utilization of G. burmanicum.

Live biotherapeutic products (LBPs) represent a distinct category of biological products containing viable organisms, such as bacteria, utilized for the prevention and treatment of human diseases (excluding vaccines). Presently, research and development efforts in LBPs are predominantly centered on live bacteria. Compared to traditional drugs, the LBPs demonstrate unique characteristics, including replicability, target specificity, and responsiveness. Owing to these properties, LBPs have emerged as hotspots in the development of specialized treatments for various major diseases, with applications spanning malignant tumors, metabolic disorders, inflammatory bowel diseases, genetic defects, and more. Nevertheless, natural bacteria face inherent limitations—such as low activity, instability, and safety concerns—that hinder their pharmacological potential. As a result, engineering strategies have become essential for enhancing the properties of bacteria and facilitating their clinical applications. This article delves into recent advancements in LBPs derived from engineered bacteria, offering a systematic review of reported engineering strategies, which are broadly categorized into chemical, physical, and genetic modifications. The findings indicate that no single engineering approach can comprehensively address all the challenges associated with converting viable bacteria into effective LBPs. To overcome this limitation, a concept of "multi-engineered bacteria" is introduced. This framework advocates for the integration of physical, chemical, and biological engineering strategies to develop next-generation LBPs with enhanced functionality and clinical potential. This article provides a concise review of current research on LBPs based on engineered bacteria and outlines forward-looking perspectives for advancing their development through innovative engineering approaches.

Bacterial infectious diseases persistently pose severe threats to human health, development of livestock and aquaculture industries, and ecological stability. The extensive use of conventional antibiotics has led to increasingly critical issues of bacterial resistance, making the development of novel and effective strategies for preventing and treating bacterial infections an urgent priority. Bdellovibrio bacteriovorus, as a genus of parasitic bacteria that prey on other bacteria, exhibits lytic activity against various pathogenic species and demonstrates potential for combating bacterial infections. However, the direct application of B. bacteriovorus suspensions or powders faces challenges including rapid clearance, susceptibility to immune system elimination, difficulty in maintaining their vitality, and poor user compliance. Recent advancements in engineered B. bacteriovorus technology have created new opportunities for more precise and efficient utilization of these predators in infection control. This paper reviews recent advances in engineered B. bacteriovorus for bacterial infection control, with particular emphasis on engineering strategies based on formulation design, surface modification, and genetic editing, along with their therapeutic applications. The review aims to provide valuable insights for advancing research on engineered B. bacteriovorus technologies.

Lymphocyte activation gene 3 (LAG-3) is an important inhibitory receptor on T cells, which plays a crucial role in tumor immune evasion. LAG-3 is primarily expressed on activated T cells, natural killer (NK) cells and B cells, et al. By binding to its ligands, LAG-3 inhibits T cell proliferation, activation, and effector functions. LAG-3 has emerged as the third immune checkpoint protein (ICP) used in clinical practice, following programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Currently, there has been at least 20 LAG-3-targeted drugs undergoing clinical trials. This article mainly reviews the structure, expression regulation, ligands, co-expressed ICP of LAG-3, as well as its application in tumor immunotherapy, and discusses the current challenges of targeting LAG-3 research.

Pulmonary fibrosis (PF) is a lung disease with a very poor prognosis that seriously affects the quality of life of patients and is characterized by scarring and thickening of the tissue surrounding the alveolar walls, ultimately leading to respiratory failure. Currently, the Food and Drug Administration (FDA) approved drugs for the treatment of PF include pirfenidone and nidazanib, however, these two drugs can only delay the progression of the disease but cannot achieve the reversal of PF, and their clinical application is limited due to high price and multiple adverse effects. The pathogenesis of PF has not been fully elucidated, and studies have demonstrated that aberrant immune cell activation and regulation play an important role in PF. This review aims to discuss the role of immune cell activation and regulation in PF in recent years. The aim of this review is to discuss recent advances in the study of the role of immune cells in the process of PF, with the aim of providing theoretical guidance for the development of novel immunotherapies.