1.Protective Effect of Xuebijing on Lung Injury in Rats with Severe Acute Pancreatitis by Blocking FPRs/NLRP3 Inflammatory Pathway
Guixian ZHANG ; Dawei LIU ; Xia LI ; Xijing LI ; Pengcheng SHI ; Zhiqiao FENG ; Jun CAI ; Wenhui ZONG ; Xiumei ZHAO ; Hongbin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):113-120
ObjectiveTo explore the therapeutic effect of Xuebijing injection (XBJ) on severe acute pancreatitis induced acute lung injury (SAP-ALI) by regulating formyl peptide receptors (FPRs)/nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammatory pathway. MethodsSixty rats were randomly divided into a sham group, a SAP-ALI model group, low-, medium-, and high-dose XBJ groups (4, 8, and 12 mL·kg-1), and a positive drug (BOC2, 0.2 mg·kg-1) group. For the sham group, the pancreas of rats was only gently flipped after laparotomy, and then the abdomen was closed, while for the remaining five groups, SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate (Na-Tc) via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling, and the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in plasma was measured by enzyme-linked immunosorbent assay (ELISA). The amount of ascites was measured, and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin (HE) staining to observe pathological changes and then scored. The protein expression levels of FPR1, FPR2, and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1, FPR2, and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of FPR1, FPR2, and NLRP3 in lung tissue. ResultsCompared with the sham group, the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue (P<0.01), serious pathological changes of lung tissue, a significantly increased pathological score (P<0.01), and significantly increased protein and mRNA expression levels of FPR1, FPR2, and NLRP3 in lung tissue (P<0.01). After BOC2 intervention, the above detection indicators were significantly reversed (P<0.01). After treatment with XBJ, the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue, which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.
2.Optimization Strategy and Practice of Traditional Chinese Medicine Compound and Its Component Compatibility
Zhihao WANG ; Wenjing ZHOU ; Chenghao FEI ; Yunlu LIU ; Yijing ZHANG ; Yue ZHAO ; Lan WANG ; Liang FENG ; Zhiyong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):299-310
Prescription optimization is a crucial aspect in the study of traditional Chinese medicine (TCM) compounds. In recent years, the introduction of mathematical methods, data mining techniques, and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables, including the proportions of different herbs, the specific extraction parts of each ingredient, and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context, it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues, such as the optimization of source material selection, dosage optimization of compatible herbs, and multi-objective optimization indicators, were discussed. Furthermore, the evaluation methods for component effects were summarized during the optimization process, so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.
3.Effect and mechanism of compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis in T2DM insulin resistance rats
Shuang WEI ; Feng HAO ; Wenchun ZHANG ; Zhangyang ZHAO ; Ji LI ; Dongwei HAN ; Huan XING
China Pharmacy 2025;36(1):57-63
OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus (T2DM) insulin resistance (IR) rats. METHODS Sixty male SD rats were randomly divided into control group (12 rats) and modeling group (48 rats). The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group, the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group, 4.05 g/(kg·d), intragastric administration], ferroptosis inhibitor ferrostatin-1 group [Fer-1 group, 5 mg/kg by intraperitoneal injection, once every other day], the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group, 4.05 g/(kg·d) by intragastric administration+erastin 10 mg/(kg·d), intraperitoneal injection]. After 4 weeks of intervention, serum fasting blood glucose (FBG) and fasting insulin (FINS) were measured in each group of rats, and homeostasis model assessment of insulin resistance (HOMA-IR) and the natural logarithm of insulin action index(IAI) were calculated; the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate transaminase (AST) and alanine transaminase (ALT), Fe2+ and Fe content, glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels, NADP+/NADPH ratio and reactive oxygen species (ROS) were determined. The pathological morphology of its liver tissue was observed; the protein expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), long-chain acyl-CoA synthetase 3 (ACSL3), ACSL4, ferritin mitochondrial (FTMT), and cystine/glutamate anti-porter (xCT) in the liver tissue of rats were detected. RESULTS Compared with control group, the liver cells in the model group of rats showed disordered arrangement, swelling, deepened nuclear staining, and more infiltration of inflammatory cells, as well as a large number of hepatocyte vacuoles and steatosis; FBG (after medication), the levels of TC, TG, LDL-C, AST, ALT, FINS, MDA and ROS, HOMA-IR, Fe2+ and Fe content, NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated, while the levels of HDL-C, GSH and SOD, IAI, protein expressions of GPX4, FTH1, ACSL3, FTMT and xCT were significantly reduced or down-regulated (P<0.01). Compared with the model group, both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators, the differences in the changes of most indicators were statistically significant (P<0.01 or P<0.05). Compared with QG group, the improvement of the above indexes of QG+erastin group had been reversed significantly (P<0.01). CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats, and alleviate IR degree, ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.
4.Strengthening the construction of hospitals' organ donation and transplantation work systems and the ethics committees for organ transplantation in accordance with laws and regulations
Feng HUO ; Hongtao ZHAO ; Xiaomei ZHAI
Organ Transplantation 2025;16(1):52-58
The implementation of the "Regulations on Organ Donation and Transplantation" (hereinafter referred to as the new "Regulations") and supporting documents has laid a solid foundation for improving the organ donation and transplantation work system in accordance with laws and regulations. In order to better publicize, implement, and carry out the new "Regulations" and supporting documents, and in response to the problems and challenges encountered in actual work, combined with the development of the national human organ donation and transplantation work system and the national work on determination of brain death, this article analyzes and discusses the construction of hospitals' organ donation and transplantation work systems and the systematic multidisciplinary collaboration mechanism for organ donation, as well as several issues that need attention by the ethics committees for organ transplantation. The aim is to provide references for the construction of ethics committees for organ transplantation in China and to promote the continuous and healthy development of China's organ donation and transplantation cause.
5.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
6.Research progress in the application of supercooling preservation technology in graft preservation
Heng ZHAO ; Jinteng FENG ; Bangrui YU ; Yixing LI ; Haotian BAI ; Haishui HUANG ; Guangjian ZHANG
Organ Transplantation 2025;16(3):394-403
Supercooling preservation technology, as a groundbreaking innovation in the field of organ preservation, significantly reduces the metabolic rate of cells and inhibits ice crystal formation by placing organs in a low-temperature environment near or below the freezing point. This technology extends the preservation time of organs and maintains their biological activity. Compared with the traditional low-temperature preservation at 4 °C, supercooling preservation effectively avoids cell damage and the accumulation of metabolic products, demonstrating significant advantages in the preservation of cells, tissues and organs. In recent years, important progress has been made in the optimization of cryoprotectants, the application of antifreeze proteins, the improvement of vitrification technology, and the development of nanotechnology-based rewarming techniques. These advancements provide new pathways to address the challenges of toxicity, ice crystal formation and uneven rewarming rates during supercooling preservation. This review summarizes the basic principles of supercooling preservation, the application of key technologies, and their practical effects in organ transplantation. It also analyzes the challenges of toxicity and rewarming efficiency, aiming to provide theoretical support and research directions for the future optimization of organ low-temperature preservation technology and its clinical application.
7.Research on BP Neural Network Method for Identifying Cell Suspension Concentration Based on GHz Electrochemical Impedance Spectroscopy
An ZHANG ; A-Long TAO ; Qi-Hang RAN ; Xia-Yi LIU ; Zhi-Long WANG ; Bo SUN ; Jia-Feng YAO ; Tong ZHAO
Progress in Biochemistry and Biophysics 2025;52(5):1302-1312
ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.
8.Regulation of Ferroptosis by Traditional Chinese Medicine for Colorectal Cancer Intervention: A Review
Xiangchen LIU ; Weihan ZHAO ; Feixue FENG ; Xiaodong YANG ; Zhilong ZHAO ; Dezhen YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):276-286
Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients, problems such as low quality of life, obvious side effects, and unsatisfactory clinical efficacy still exist, which cannot fully satisfy the overall needs of patients. For this reason, it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years, with the deepening of research, ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells, overcome tumor drug resistance, enhance anti-tumor efficacy, and prevent tumor progression and recurrence. Therefore, regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine (TCM) has been widely used in CRC treatment due to its advantages of multiple components, multiple targets, low drug resistance, and few side effects, and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways, such as iron metabolism, lipid metabolism, the cystine/glutamate antiporter system Xc- (System Xc-)/glutathione (GSH)/glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10)/nicotinamide adenine dinucleotide phosphate [NAD(P)H], tumor protein 53 (p53), nuclear factor erythroid-2-related factor 2 (Nrf2), and non-coding RNA pathways to inhibit the growth and proliferation of CRC, thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC, therapeutic targets and prognosis-related markers associated with ferroptosis in CRC, and research progress on TCM targeting and regulating ferroptosis for CRC intervention, aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.
9.Prognostic analysis of genes related to pyroptosis in prostate cancer cells and the regulatory role of NLRP1
Xiaolu MA ; Jiaqin CHEN ; Junlong FENG ; Qi ZHAO ; Bin WANG
Journal of Modern Urology 2025;30(1):73-81
[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.
10.Pharmacokinetic Analysis of Ziyuglycoside Ⅰ in Normal and Acute Kidney Injury Rats
Yunhui ZHANG ; Yanli LIU ; Qiongming XU ; Shuding SUN ; Hongjin ZHU ; Di ZHAO ; Suxiang FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):203-210
ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry(UPLC-Orbitrap Fusion Lumos Tribrid-MS), the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration, and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group, the model group received intraperitoneal cisplatin(10 mg·kg-1) to establish the acute kidney injury model, the normal group was given the same volume of saline. After successful modeling, rats in the normal and model groups were randomly divided into the normal low, medium and high dose groups(2.5, 5, 7.5 mg·kg-1) and the model low, medium and high dose groups(2.5, 5, 7.5 mg·kg-1), 6 rats in each group, and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then, the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS, and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software, and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ, its concentration increased first and then decreased, and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve(AUC0-t) and mean retention time(MRT0-t) of normal and model rats increased with the increased dose, and the clearance(CL) decreased with the increasing dose. Compared with the normal group, the AUC0-t was significantly increased(P<0.01), peak concentration(Cmax) and CL decreased in model rats at different doses, indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats, which may be due to the change of the body environment in the pathological state, then lead to changes in absorption and metabolic processes.

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