2',4'-Dimethoxychalcone (DMC) is a structural modifier of carvacrol B. In this study, gastric cancer cells MGC-803 and HGC-27 were used as the subjects to investigate the anti-tumor effect and mechanism of DMC on gastric cancer (GC) cells both in vitro and in vivo. DMC inhibited cell viability and cell proliferation and promoted cell apoptosis in GC cells, detected by CCK-8 assay, EdU staining and Annexin V-FITC/PI double-staining flow cytometry. A nude mouse model of GC cell xenograft was constructed by subcutaneous injection with MGC-803 cells, for measuring the effect of DMC on the growth of GC in vivo, and DMC inhibited the growth of subcutaneous transplantation tumor in nude mice. The animal experiments were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine under the ethical number PZSHUTCM2310110002. The effect of DMC on the RNA expression of MGC-803 cells was detected by RNA-seq assay, and it was found that the biological function of DMC was enriched in glycolysis. DMC inhibited the glucose uptake capacity and lactate production and efflux of gastric cancer cells, detected by using 2-NBDG probe with flow cytometry and lactate (LD) test kit. Western blot assay was performed to detect the protein expression of proliferation, apoptosis, and glycolysis-related proteins in gastric cancer cells, and the results demonstrated that DMC up-regulated the protein expression of cleaved caspase-9, cleaved caspase-3, cleaved PARP, down-regulated Ki-67 protein expression, and inhibited the protein expression of c-Myc, LDHA, GLUT3, PDHK1 and MCT1 in gastric cancer cells. The Seahorse energy metabolism analyser was used to measure the rate of glycolysis, and it was found that DMC could down-regulate the basal glycolysis rate and compensatory glycolysis in gastric cancer cells. The c-Myc overexpressing cell line MGC-803 was used in the reversal experiment to further confirm that DMC suppressed gastric cancer growth through inhibiting c-Myc mediated glucose uptake and glycolysis. In conclusion, DMC may inhibit the protein expression of c-Myc and its target glycolysis-related genes, suppressed c-Myc-mediated glucose uptake and glycolysis in gastric cancer cells, thereby inhibited the cell proliferation and promoted cell apoptosis of gastric cancer cells, and thus finally inhibited the growth of gastric cancer in vivo and in vitro.

Plasma exosomes (Pla-Exos) were extracted from rats by ultracentrifugation. The ultracentrifugation method extracted rat Pla-Exos at a speed of 150 000 ×g for 2.5 h. Various purification methods including ultracentrifugation, magnetic bead capture method, and ultrafiltration would be employed to purify Pla-Exos. The Pue-Exos were prepared via sonication-assisted and co-incubation methods. The influence factors and levels of the preparation of plasma exosomes carrying puerarin (Pue-Exos) were investigated by RSM plus CCD method with encapsulation rate as an index. Then the characterization, the stability, and in vitro release of Pue-Exos were determined. The particle sizes of exosomes purified by ultracentrifugation, ultrafiltration, or magnetic bead capture method were all within the range of 30-150 nm. The Western blot results showed that purified Pla-Exos and Pue-Exos contained marker proteins TSG101, CD63, and CD81. The TEM showed that purified Pla-Exos and Pue-Exos exhibited well-defined double-layered membrane vesicle structures. The optimal prescription conditions for preparing Pue-Exos were finally determined as follows: 1 h ultrasound time, 39 W ultrasound power, mass ratio of 10∶1. The prepared Pue-Exos exhibit good stability and sustained release, significantly enhancing the in vitro transpermeability of puerarin across the blood-brain barrier (P < 0.01). This study was approved by the Experimental Animal Ethics Review Committee of Hebei North University, and ethics approval number was HBNV202307012103.

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.

Liver fibrosis is a chronic liver injury caused by various pathogenic factors, leading to excessive accumulation of extracellular matrix such as collagen. It represents a common pathological hallmark during the progression of most chronic liver diseases. However, there is currently no universally recognized specific and effective drug for the clinical treatment of liver fibrosis. Therefore, this study investigates the effects of Alisma Rhizoma on bile duct ligation (BDL)-induced liver fibrosis and explores the potential pharmacological mechanisms. The animal experimental protocol was reviewed and approved by the Animal Welfare and Ethics Committee of Shanghai University of Traditional Chinese Medicine (registration No. PZSHUTCM2303280007), in compliance with relevant animal welfare and ethical standards. Mice were subjected to BDL to induce liver fibrosis. Mice were divided into five groups: sham operation group (Sham), model group (BDL), ethanol extract protection group (BDL+EE, 1.6 g·kg^-1), water extract protection group (BDL+WE, 4.0 g·kg^-1), obeticholic acid protection group (BDL+OCA, 10 mg·kg^-1). The results showed that both of EE and WE could attenuate BDL-induced liver fibrosis as evident by reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) activities, total bile acids (TBA) levels, and improved pathological conditions such as cholestasis, collagen deposition, inflammatory cell infiltration, and liver tissue necrosis. Notably, EE showed better efficacy than WE. Further studies showed that EE improved liver fibrosis dose dependently. EE treatment impaired the bile acids homeostasis in serum and liver, and recovered the hepatic mRNA expression of farnesoid X receptor (FXR) as well as the downstream genes including small heterodimer partner (SHP), cholesterol 7-alpha hydroxylase (CYP7A1) and bile salt export pump (BSEP). Further study also proved that the four major triterpenes in EE increased the transcriptional activities of FXR in vitro. This study provides a theoretical basis for the clinical application of Alisma Rhizoma in the prevention and treatment of liver fibrosis.

Radiation enteritis (RE) is the most common complication during radiotherapy, although safe and effective drugs for the treatment of RE are deficient. Probiotics have been demonstrated to own antiradiation function. Synbiotics are composed of probiotics and prebiotics, which enhance the ability of probiotics. Here, inulin gel (IG) that own the ability to resist gastric acid and retain in the colon were used to load three types of probiotics, including Bacillus cereus (BC), Bacillus licheniformis (BL), and Lactobacillus reuteri (LR), respectively. The RE pharmacodynamic studies of them were conducted. The probiotics were embedded in the IG by scanning electron microscopy and confocal laser scanning microscopy. IG promoted the growth of probiotics compared to probiotics alone. Animal experiments were approved by the Ethics Committee of the Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations (No. IACUC-DWZX-2024-P510). Mice experienced the whole abdominal irradiation of 13 Gy γ rays to form RE models. Compared to correspondingly probiotics alone, all probiotic-loaded IG synbiotics had the better prevention and treatment efficiencies in repairing the intestinal barriers, improving the structure of crypts, oxidative stress, inflammation, and imbalanced gut microbiota and promoting the recovery of intestinal villus, where the Bacillus cereus-loaded IG was the best. This study provides a novel therapeutic for the prevention and treatment of RE.

In the early stage of the project, it was found that natural pentacyclic triterpenes liquidambaric acid regulates the NEDD8 modification of Cullin2. This study aims to find more triterpenoid natural active molecules targeting Cullin family members and reveal its mechanism of action. Western blot was used to detect natural products that can significantly change the total protein NEDD8 modification and specific Cullin protein NEDD8 modification in cells; microscale thermophoresis (MST) was used to detect the direct binding of candidate small molecule oleanonic acid to TRAF family proteins, and the binding at the level of living cells was verified by cellular thermal shift assay (CETSA). Proximity ligation assay (PLA) was used to investigate the regulatory effect of oleanonic acid on the protein interaction between TNF receptor-associated factor 1 (TRAF1) and Cullin1 NEDD8 modified complex. Three pentacyclic triterpenoids were found to significantly inhibit NEDD8 modification in cells, among which oleanonic acid had the strongest effect on blocking NEDD8 modification. Different from the previous identification that liquidambaric acid regulates Cullin2/5, oleanonic acid can also specifically induce NEDD8-modified Cullin1 to transform into its unmodified form. And binding experiments showed that oleanonic acid could directly bind to TRAF1 at the level of cell lysate and living cells. Further mechanism studies found that oleanonic acid significantly changed the protein interaction between TRAF1 and Cullin1 NEDD8 modified complex. The above results indicate that oleanonic acid targets TRAF1 and regulates its interaction with NEDD8 modification complex to inhibit NEDD8 modification of Cullin.

High-altitude sleep disturbance is a common acute high-altitude disease that can trigger physiological discomfort such as acute high-altitude reactions, with a lack of safe and effective preventive medications in clinical practice. Based on the gut-brain axis theory, this study designed and prepared a synbiotics combining Lactobacillus rhamnosus (LGG)-Lycium barbarum polysaccharide (LBP). First, the LGG-LBP synbiotics was prepared and evaluated. The mice were randomly divided into healthy, model, positive control (acetazolamide), LBP, LGG and LGG-LBP synbiotics group. After 7 days of administration, the mouse model of high-altitude sleep disturbance was established, the treating effects were evaluated through sleep duration, behavioral, hemogram test, and the content of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in blood. 16S rRNA sequencing was used to analyze the changes of gut microbiota, and the pathological changes of small intestine were observed. The LGG-LBP synbiotics prolonged sleep duration, improved exploratory ability and short-term memory, promoted blood cell recovery. Moreover, LGG-LBP synbiotics enhanced the abundance of probiotics in the gut, and reduced intestinal inflammation. LGG-LBP synbiotics may be a potential prophylactic drug for high-altitude sleep disturbance. The animal operation was approved by the Ethics Committee of the Academy of Military Medical Sciences, Academy of Military Science (Approval number: IACUC-DWZX-2022-511). All experiments were conducted in accordance with relevant guidelines and regulations.

With the increasing abuse of antibiotics and the growing resistance of bacteria, it is urgent to find new antibacterial agents. Numerous constituents of traditional Chinese medicine exhibit pronounced antibacterial, anti-inflammatory, and antioxidant pharmacological properties, often operating through multiple mechanisms, thereby positioning them as a vital source for the development of novel antibacterial agents in the future. Nevertheless, the antibacterial constituents of traditional Chinese medicine exhibit challenges such as inadequate stability, low solubility, and suboptimal intelligent release capabilities, which hinder their extensive application in antibacterial formulations. Metal-organic framework materials serve as highly effective drug carriers for antibacterial constituents of traditional Chinese medicine, attributed to their high specific surface area, elevated porosity, controllable pore dimensions, and responsive release properties. Furthermore, they not only enhance the stability and solubility of these antibacterial constituents while also exhibiting inherent antibacterial activity and responsive release capabilities. This paper presents a comprehensive overview of bacterial resistance mechanisms and the action pathways of antibacterial constituents of traditional Chinese medicine against resistant bacteria. Additionally, it highlights the current advancements in metal-organic framework materials and their application in the delivery systems for these antibacterial constituents, aiming to provide valuable insights for the research and innovation of formulations based on traditional Chinese medicine.

Nutlin-3 is a representative small molecule MDM2-p53 antagonist, which can stabilize the p53 state by disrupting the interaction between p53 and MDM2, thereby inducing the p53 signaling pathway to exert antitumor effects. In this study, six wild-type p53 tumor cell lines, HCT-116, H460, HepG2, MCF-7, A549 and SJSA-1, were used as research objects, and the effects of nutlin-3 on the proliferation of six wild-type p53 cancer cells were detected by methyl thiazolyl tetrazolium (MTT) method and plate cloning assay. The effects of nutlin-3 on H460 cell cycle and apoptosis were detected by flow cytometry. Western blot assay was used to detect ubiquitin-specific protease 7 (USP7), death domain-associated protein (DAXX), murine double minute 2 (MDM2), murine double minute 4 (MDMX/ MDM4), p53, to explore the anti-tumor mechanism of nutlin-3; co-immunoprecipitation (Co-IP) assay was used to detect the effect of nutlin-3 on the interaction between MDM2, MDMX and p53. The results showed that nutlin-3 inhibited the proliferation of H460 in a time- and concentration-dependent manner. The results of cell cycle and apoptosis showed that nutlin-3 could block the H460 cell cycle in the G0/G1 phase, and induce apoptosis by activating cleaved-PARP. Western blot results showed that nutlin-3 could up-regulate the expression of USP7, DAXX, MDM2, MDMX and p53 in H460 cells. Co-IP results showed that nutlin-3 inhibited the protein interactions between MDM2 and p53 and MDM2 and MDMX. In conclusion, nutlin-3 can significantly inhibit the proliferation of wild-type p53 cancer cells and induce cell cycle arrest and apoptosis, which may be related to the disruption of MDM2/MDMX's interaction with p53 to activate the MDM2-p53 signaling pathway.

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.