Natural products have shown great potential in the research and development of antitumor drugs. However， their clinical application is severely limited by inherent drawbacks such as poor water solubility， low stability， and low bioavailability. Cell membrane biomimetic nanoparticles， as a novel drug delivery system， have provided new strategies to overcome this bottleneck. This review systematically summarizes the preparation methods （e.g.， membrane extrusion， ultrasonic fusion， and microfluidic electroporation） and characterization techniques （e.g.， particle size， Zeta potential， and membrane surface protein detection） of cell membrane biomimetic nanoparticles， with a focus on the application of these derived from various sources in delivering antitumor natural products. Cell membrane biomimetic nanoparticles are endowed with unique biological functions， including low immunogenicity conferred by stem cell membranes， prolonged systemic circulation enabled by red blood cell membranes， and homologous targeting facilitated by tumor cell membranes. Despite these advancements， the technology still faces challenges such as difficulties in large-scale production， high costs， and limited characterization methods. Future research needs to further optimize the relevant processes to promote the clinical translation of cell membrane-biomimetic nanoparticles， thereby offering an efficient and safe novel delivery approach for antitumor therapy using natural products.

Objective To establish an efficient,sensitive,and accurate ion chromatography method for the simultaneous determination of three impurity ions—bromide(Br-),nitrite(NO2-),and oxalate(C2 O42-)—in oral rehydration salts powder(Ⅲ).These impurity ions may pose potential toxic side effects on children's health;therefore,ensuring their content within safe limits is crucial for safeguarding pediatric medication safety.Methods A Metrosep A Supp 5 column(250 mm×4.0 mm,5 μm),packed with quaternary ammonium-bonded polyvinyl alcohol was used.The eluent consisted of carbonate buffer:Mobile phase A was a mixture of 3.2 mmol·L-1 sodium carbonate and 1.0 mmol·L-1 sodium bicarbonate(50∶50,V∶V),and mobile phase B was a mixture of 32 mmol·L-1 sodium carbonate and 10 mmol·L-1 sodium bicarbonate(50∶50,V∶V),with gradient elution.The column temperature was set at 35℃,and the flow rate was 0.7 mL·min-1.Limits for the three impurity ions were set according to the International Council for Harmonisation guidelines(ICH M7(R1)and ICH Q3B),and the method was validated by testing six actual samples.Results Within the concentration range of 0.02-0.50 μg·mL-1,the linear correlation coefficients(R2)for the three impurity ions were all greater than 0.999.The detection limits ranged from 1.2 to 3.4 ng·mL-1,and the spiked recovery rates were between 92.0%and 102.0%.Results from the six actual samples demonstrated that the method effectively controlled the content of impurity ions.Conclusion This study successfully established a gradient elution ion chromatography method for the simultaneous determination of three impurity ions in Oral rehydration salts powder(Ⅲ).The method is highly sensitive,specific,and accurate.

The inflammatory response is a natural defense mechanism of the body that occurs in response to infection or injury,serving as a critical starting point for the onset and progression of various diseases.Glycolysis,an essential pathway for energy production within the body,plays a pivotal role in both the initiation and advancement of the inflammatory response.Pyruvate kinase M2(PKM2),recog-nized as a key rate-limiting enzyme in glycolysis,not only contributes to the inflammatory process by mediating glycolysis and lactylation modifications through such mechanisms as nuclear translocation and dimer formation,but also regulates the inflammatory response by modulating immune responses in B cells,T cells,macrophages,and neutrophils.This review aims to summarize the mechanisms involved in targeting PKM2 to suppress inflammation,providing new insights into the prevention and treatment of inflammatory reactions.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To explore and establish the bacterial endotoxin limit value and testing method of the active pharmaceutical ingredient （API） of pentetic acid, and conduct methodological investigation. Methods Three batches of pentetic acid were used to establish the method for the determination of bacterial endotoxin, and interference test was conducted simultaneously. The sample was dissolved with commercially available alkaline regulator to a concentration of 4 mg/ml or lower, and then diluted with water for bacterial endotoxin test. Limulus reagent with sensitivity of 0.125 EU/ml or higher was selected and redissolved with commercially available magnesium ion buffer solution. And the endotoxin test was performed by gel method. Results The endotoxin limit of API of pentetic acid was determined as: less than 0.125 EU/mg. Conclusion The method established could be used for the control of bacterial endotoxin in API of pentetic acid.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Oral cancer is a common inflammation-associated malignant tumor of the head and neck.In recent years,the role of the tumor microenvironment in the progression of oral cancer has received increasing attention.In the microenvironment of solid tumors,including or-al cancer,tumor-associated macrophages(TAMs)are among the most common type of immune cell and are closely associated with the poor prognosis of more than 80%of human malignant tumors.An increasing body of evidence indicates that TAMs play important roles in the oc-currence and progression of oral cancer.On the basis of the most recent research progress,both domestic and international,we systematic-ally reviewed the phenotypic characteristics,clinicopathological correlations,and molecular regulatory mechanisms of TAMs in the microen-vironment of oral squamous cell carcinoma(OSCC).In particular,we focus on the key signaling pathways promoting tumorigenesis and de-velopment and immune escape mechanisms,with the aim of constructing a systematic theoretical framework for developing therapeutic strategies targeting TAMs and providing a scientific basis for clinical translational research.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

The inflammatory response is a natural defense mechanism of the body that occurs in response to infection or injury,serving as a critical starting point for the onset and progression of various diseases.Glycolysis,an essential pathway for energy production within the body,plays a pivotal role in both the initiation and advancement of the inflammatory response.Pyruvate kinase M2(PKM2),recog-nized as a key rate-limiting enzyme in glycolysis,not only contributes to the inflammatory process by mediating glycolysis and lactylation modifications through such mechanisms as nuclear translocation and dimer formation,but also regulates the inflammatory response by modulating immune responses in B cells,T cells,macrophages,and neutrophils.This review aims to summarize the mechanisms involved in targeting PKM2 to suppress inflammation,providing new insights into the prevention and treatment of inflammatory reactions.