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.

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.

Four terpenoids were isolated from the neutral portion of petroleum ether extract of Artemisia annua by several chromatographic methods, such as silica gel, MCI Gel CHP-20, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were identified by HR-MS and nuclear magnetic resonance spectroscopy. These compounds were defined as (1S,4S,5R,6S,9R,10R)-4-ethoxy-9,10-dimethyloctahydrofuro-(3,2-i)-isochromen-11(4H)-one (1), 3a,4,5,6,6a,7-hexahydro-3,6-dimethyl-9-methyl-2H-naphtho[8a,1-b]furan-2,8(3H)-dione (2), kobusone (3) and 1,2-campholide (4). Compound 1 is a new compound, of which the absolute configuration was established by single crystal X-ray crystallographic analysis. Compound 2 is a new natural product. Compounds 3 and 4 are first isolated from the Artemisia genus.

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.

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.

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.

Oxaliplatin (Oxa) is a chemotherapy drug commonly used for advanced colorectal cancer, however most patients develop resistance after treatment while the mechanisms of which have not been fully elucidated. In this study, oxaliplatin resistant cell lines were constructed from human colorectal cancer HCT116 cells through concentration gradient induction. On this basis, we investigated the expression profiling of HCT116/Oxa cells based on quantitative proteomics. Gene ontology (GO) analysis was conducted via The Database for Annotation, Visualization, and Integrated Discovery Database (DAVID), and pathway enrichment analysis was done using GeneAnalytics database. The potential targets and molecular mechanisms of oxaliplatin resistance in colorectal cancer were further studied by inhibitors, Western blot and siRNA. The results showed that the oxaliplatin resistance index of HCT116/Oxa cells was 10.2. HCT116/Oxa cells demonstrated stronger proliferation potential and anti-apoptotic capacity to oxaliplatin compared with HCT116 cells. Proteomic data demonstrated significant expression change of 717 genes in HCT116/Oxa cells, among which 399 genes were up-regulated while 318 ones down-regulated comparing with HCT116 cells. GO enrichment analysis showed that differentially expressed genes were mainly related to biological processes such as oxidative stress response, iron metabolism, lipid metabolism, apoptosis and cell cycle progression. Pathway analysis displayed notable changes of cell metabolism, ferroptosis, Nrf2-ARE signaling, fatty acid and glutathione metabolism in HCT116/Oxa cells. Quantitative results indicated that the expression of proteins directly related to ferroptosis, including glutathione peroxidase 4 (GPX4), glutamate-cysteine ligase regulatory subunit (GCLM), ferritin light chain (FTL), ferritin heavy chain (FTH1), heme oxygenase 1 (HMOX1), glutathione reductase (GSR) and NADH dehydrogenase 1 (NQO1) increased, while long chain fatty acid-CoA ligase (ACSL) 4 and ACSL1 decreased significantly in HCT116/Oxa cells. Functional studies showed that RSL3, a specific inhibitor of GPX4, decreased the viability of drug-resistant cells, improved lipid peroxidation, increased the concentration of ferrous ions, malondialdehyde, and decreased the concentration of glutathione (GSH). Western blot showed that the expressions of GPX4, FTH1, FTL and GSR increased in HCT116/Oxa, while ACSL4 decreased. RSL3 reversed the levels of GPX4, FTH1, FTL, GSR and ACSL4. It was further found that knockdown of GPX4 decreased the viability of drug-resistant cells, increased lipid peroxidation levels and decreased GSH concentration. These results suggest that ferroptosis resistance mediated by GSH/GPX4 pathway may be a potential mechanism of oxaliplatin resistance in HCT116/Oxa, and inhibition of GSH/GPX4 signaling could be an effective approach to reverse oxaliplatin resistance in colorectal cancer.

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.

Fourteen compounds including two new compounds were isolated from Kronopolites svenhedini (Verhoeff). These structures were identified as kronoponit A (1), kronoponit B (2), neoechinulin A (3), 2-(1, 1-dimethyl-2-propen-1-yl)-1H-indole-3-carboxaldehyde (4), uracil (5), p-hydroxy phenyl ethylamine (6), p-hydroxyphenylacetic acid (7), p-hydroxybenzoic acid (8), p-ethylbenzoic acid (9), 2-methyl-1, 4-benzenediol (10), 1, 2, 4-benzenetriol (11), gallic acid (12), gallic acid-3-methyl ether (13), and 4-methoxy-3, 5-hydroxybenzoic acid (14) by spectroscopic methods and literature. Among them, compounds 1 and 2 are new, while compounds 3-14 are reported here for the first time from K. svenhedini.

Indigo naturalis [Baphicacanthus cusia (Nees) Bremek., QD], as a traditional Chinese medicine, has exhibited efficacy in the ulcerative colitis (UC). Cu Dian (CD), the current form of Indigo naturalis, has been regarded as the mainstream form of medicine today. Dian Hua (DH) is the traditional purified form of QD, in which the content of indigo and indirubin is higher than that of CD. The study evaluated the efficacy of DH and CD in UC and explored their mechanism. Male BALB/c mice were subjected to an 8-day regimen of 3% dextran sodium sulphate (DSS) drinking water to induce UC. The experiment was approved by the Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine (approval number: 2024075). Concurrently, the mice received intragastric administration of CD (400, 200, and 100 mg·kg^-1) and DH (400, 200, 100, and 50 mg·kg^-1) for the same duration. The anti-inflammatory properties of CD and DH were evaluated by quantifying levels of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18 in colon tissue. Western blot and immunofluorescence assays were employed to assess the protein levels of zonula occludens 1 (ZO-1) and occludin. Additionally, Western blot and RT-qPCR were utilized to analyze the protein and gene expression levels of AMP-activated protein kinase (AMPK), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), and related factors in colon tissue. CD and DH demonstrated a capacity to alleviate inflammatory responses in mice with UC. The protective impact of both CD and DH on the intestinal mucosal barrier was associated with an elevation of ZO-1 and occludin. Furthermore, the anti-inflammatory effects of CD and DH were attributed to the inhibition of the NLRP3 inflammasome through the activation of the AMPK/silent information regulator of transcription 1 (SIRT1) pathway. Notably, DH exhibited a more pronounced improvement in UC compared to CD, particularly at the dosage of DH-M (200 mg·kg^-1). Our investigation substantiates the effectiveness of CD and DH in mitigating DSS-induced UC in mice. They demonstrated a capacity to diminish the production of inflammatory cytokines and safeguard the integrity of the intestinal epithelial barrier, notably by elevating level of tight junctions. The anti-colonic inflammatory effects of CD and DH were elucidated through the inhibition of both the formation and activation of the NLRP3 inflammasome, mediated by the AMPK/SIRT1 pathway.