1.Protective effect and mechanism of trophoblast-derived mesenchymal stem cells against liver injury in a mouse model of autoimmune hepatitis
Long XU ; Wanwan SHI ; Jiandan QIAN ; Shiyun KE ; Yusheng HE ; Xiaofang WANG ; Guiqiang WANG
Journal of Clinical Hepatology 2026;42(9):2116-2125
ObjectiveTo investigate the effect of trophoblast-derived mesenchymal stem cell (T-MSC) on concanavalin A (Con A)-induced immune-mediated liver injury in mice, as well as its association with the changes in inflammatory response. MethodsMorphological assessment, flow cytometry, and tri-lineage differentiation assay were used to observe the biological characteristics of T-MSC. In the pilot experiment, mice were divided into PBS group, T-MSC monotherapy group, and Con A groups at a concentration of 10, 15, or 20 mg/kg to evaluate the safety of T-MSC monotherapy on liver function and determine the appropriate dose for modeling. In the formal experiment, mice were divided into healthy control group (HC group), Con A group, and Con A+T-MSC group, with 5 mice in each group. The mice were given injection of Con A (15 mg/kg) via the caudal vein to establish a mouse model of immune-mediated liver injury, while the mice in the T-MSC monotherapy group were given transfusion of 1×106 T-MSCs via the caudal vein at 3 hours after modeling, and samples were collected 12 hours later. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured; liver histopathological changes were observed, and Ishak inflammatory activity score and inflammatory necrosis area were assessed; the serum levels of inflammatory cytokines were measured; transcriptome sequencing, immunofluorescence assay, and Western blot were used to measure the changes in inflammation-related molecules in liver tissue. The Shapiro-Wilk test was used to assess the normality of continuous data, and the homogeneity of variance test was also performed; a one-way analysis of variance was used for comparison of normally distributed data with homogeneity of variance between multiple groups, and the Tukey’s post-hoc test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed data with heterogeneity of variance between multiple groups, and the Wilcoxon test was used for further comparison between two groups. ResultsT-MSC had a long spindle shape, showed the characteristics of fibroblast-like morphology and adherent growth, and possessed the osteogenic, chondrogenic, and adipogenic differentiation abilities. Flow cytometry showed high expression levels of CD90, CD105, and CD73 in T-MSC, with a positive rate of 96.8%, 99.0%, and 99.9%, respectively, while there was low or no expression of CD31, human leukocyte antigen DR, CD45, and CD34, with a positive rate of 0.120%, 0, 0.061%, and 0, respectively. Administration of T-MSC alone did not cause obvious abnormalities in ALT, AST, or LDH. Con A at the concentrations of 10, 15, and 20 mg/kg all increased the serum levels of biochemical parameters for liver injury in a dose-dependent manner, with mortality observed in the 20 mg/kg group. In the formal experiment, compared with the HC group, the Con A group had significant increases in the serum levels of ALT, AST, and LDH (P<0.01), and after T-MSC treatment, there were significant reductions in these markers compared with the Con A group (P<0.01). HE staining showed that the Con A group had disordered structure of the liver, accompanied by marked inflammatory cell infiltration and focal/patchy necrosis, and these pathological changes were alleviated after T-MSC treatment. Compared with the HC group, the Con A group had significant increases in Ishak score and the percentage of inflammatory necrosis area (P<0.001), while there were significant reductions in these indicators after T-MSC treatment compared with the Con A group (P<0.01). ELISA showed that compared with the HC group, the Con A group had significant increases in the serum levels of interleukin-21 (IL-21), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-17A (IL-17A), and tumor necrosis factor-α (TNF-α) (P<0.05), and there were significant reductions in these markers after T-MSC treatment compared with the Con A group (P<0.05), with no significant differences in IL-21, IL-1β, IL-17A, and TNF-α compared with the HC group (P>0.05); although there was a significant reduction in the level of IL-2, the Con A+T-MSC group still had a significantly higher level of IL-2 than the HC group (P=0.001). In contrast, compared with the HC group, the Con A group had a significant increase in IL-10 (P<0.05), with a further increase after T-MSC treatment (P<0.05). The transcriptome analysis showed that T-MSC treatment downregulated the expression of the inflammation- and chemokine-related genes including Ccl2, Cxcl10, Il-21, and Il-6 and inhibited the inflammation-related pathways such as TNF, IL-17, nuclear factor-κB, and JAK-STAT. Immunofluorescence assay showed that compared with the HC group, the Con A group had a significant increase in the expression of IL-21 in the liver (P<0.001), and there was a significant reduction in IL-21 after T-MSC treatment compared with the Con A group (P<0.001); the results of Western blot showed the same trend. ConclusionT-MSC can alleviate Con A-induced immune-mediated liver injury in mice, as evidenced by the improvement in liver biochemical parameters, the alleviation of histopathological damage, and the overall downregulation of inflammation-related molecules. T-MSC exerts marked anti-inflammatory and immunomodulatory effects in this model, and IL-21 shows a significant change in inflammatory response and can be used as a candidate molecule for further investigation.
2.Advances in centrosome amplification and cancer development
Zhaoxue WANG ; Xin MENG ; Shiyun ZHANG ; Ke SHI ; Yucheng LU
Chinese Journal of Pathophysiology 2025;41(10):2038-2045
Centrosome amplification is a hallmark of malignant tumours and has been established as a critical carcinogenic factor driving the progression of various malignancies.This review systematically outlines the structural com-position and replication cycle of the centrosome,thoroughly analyses the specific manifestations of abnormal centrosome amplification in tumor cells,and explores the molecular mechanisms underlying centrosome amplification.Furthermore,this review highlights therapeutic strategies targeting abnormal centrosome expansion and their potential application in tu-mor intervention.In-depth investigations of centrosome amplification mechanisms and intervention pathways may offer novel insights for early cancer diagnosis and precision therapy.
3.Pharmacological action of astragaloside Ⅳ in the prevention and treatment of liver diseases and its mechanism
Ke FU ; Shu DAI ; Juan YOU ; Chen YANG ; Xiaoli LI ; Li ZENG ; Shiyun PU
Journal of Clinical Hepatology 2025;41(10):2174-2179
Astragaloside Ⅳ (AS-Ⅳ) is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally, and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism, exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect, and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways, such as AMPK, NLRP3, NF-κB, JAK2/STAT3, and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.
4.Advances in centrosome amplification and cancer development
Zhaoxue WANG ; Xin MENG ; Shiyun ZHANG ; Ke SHI ; Yucheng LU
Chinese Journal of Pathophysiology 2025;41(10):2038-2045
Centrosome amplification is a hallmark of malignant tumours and has been established as a critical carcinogenic factor driving the progression of various malignancies.This review systematically outlines the structural com-position and replication cycle of the centrosome,thoroughly analyses the specific manifestations of abnormal centrosome amplification in tumor cells,and explores the molecular mechanisms underlying centrosome amplification.Furthermore,this review highlights therapeutic strategies targeting abnormal centrosome expansion and their potential application in tu-mor intervention.In-depth investigations of centrosome amplification mechanisms and intervention pathways may offer novel insights for early cancer diagnosis and precision therapy.
5.The value of synthetic MRI combined with diffusion weighted imaging in differential diagnosis of benign and malignant breast lesions
Shiyun SUN ; Zhuolin LI ; Lisha NIE ; Yifan LIU ; Dongxue ZHANG ; Ke XUE ; Yingying DING
Chinese Journal of Radiology 2021;55(6):597-604
Objective:To evaluate the value of synthetic MRI combined with DWI in the diagnosis of benign and malignant breast lesions.Methods:The data of 184 consecutive patients with suspected breast lesions in Yunnan Cancer Hospital from July to September 2019 were prospectively analyzed. All patients were randomly assigned to training group ( n=110) and validation group ( n=74), and underwent conventional MRI and synthetic MRI respectively before and after contrast injection. At the maximum slice of the lesion, the ROI was drawn along the edge and recorded as "tumor". In the solid area with the most obvious tumor enhancement, the second ROI was drawn and recorded as "local". At the same time, ADC values (ADC local and ADC tumor) and relaxation time values (T local and T tumor) were measured. T and T + represented the relaxation time value of the ROI pre-and post-contrast scanning. ΔT% represented the relative change rate in T value between pre-and post-contrast scanning.The rank sum test was used to test the quantitative parameters of benign and malignant breast lesions in the training group and the validation group, and the variables with P<0.05 were included in the binary logistic regression analysis to screen the independent variables and establish the prediction model. The area under ROC curve was used to evaluate the discrimination of parameters and models. The clinical applicability of model was analyzed by decision curve analysis (DCA). Results:In the training group, univariate analysis showed that there were significant differences in T 1tumor, T 1+tumor, ΔT 1% tumor, T 2local, T 2+local, T 2tumor and T 2+tumor, ADC local, ADC tumor between benign and malignant breast lesions ( P<0.05). Multivariate logistic regression analysis showed that T 1+tumor, ΔT 1% tumor, T 2tumor, ADC local, ADC tumor were independent variables in the diagnosis of breast cancer. The relaxation time model (model A: T 1+tumor, ΔT 1% tumor, T 2tumor) and ADC model (model B: ADC local, ADC tumor) established by combining the above variables had the same diagnostic efficiency (AUC=0.905, 0.914, Z=-1.874, P=0.062), and the multi-parameter combination model (model C: T 1+tumor, ΔT 1% tumor, T 2tumor, ADC local, ADC tumor) had the highest diagnostic efficiency (AUC=0.965). DCA analysis showed that when the threshold probability ranges between 21%-99% (training cohort) and 15%-99% (validation cohort), the net benefit of model C was better than model A and B. Conclusion:The multi-parameter combined prediction model established based on the relaxation time value and ADC can identify breast cancer efficiently and can be used as an auxiliary diagnostic tool.
6.Effect of Sodium ferulate on glucocorticoid-induced osteoporosis
Yang LIU ; Jun CHEN ; Yuying ZHAI ; Xiaotian YE ; Shan XIAO ; Shiyun KE ; Qingnan LI ; Guozhu YANG ; Li LU ; Xingyan LU
Chinese Pharmacological Bulletin 2016;32(3):394-398
Aim To study the influence of Sodium fer-ulate ( SF) on bone metabolism in glucocorticoid–in-duced osteoporosis rats. Methods Thirty cases of fe-male Wistar Rats(3-month-old) were divided into con-trol group, model group and SF group ( low-dose group, middle-dose group, high-dose group ) by ran-domized block design. Double fluorochrome labeling with calcein was performed before necropsy. The left tibia was taken for bone histomorphometry. Results In static parameters, the proximal tibia cancellous bone trabecular thickness, trabecular quantity and area ratio were significantly reduced in model group compared with control group;while compared with model group, those were increased in middle and high-dose SF group. Trabecular separation degree was increased in model group compared with control group, while it was decreased in middle and high-dose SF group compared with model group. In dynamic parameters, the calcula-tion parameters of cancellous bone mark perimeter rate and the bone formation rate were increased in model group compared with control group, in middle and high-dose SF group the bone formation rate was in-creased compared with model group. In bone cells, os-teoclast number per mm, osteoblast number per mm, percent osteoblast surface perimeter and percent osteo-clast surface perimeter were increased in model group compared with control group. In growth-plate, the thickness of growth-plate was increased in model group compared with control group. In bone cells and growth-plate there was no statistical significance between treat-ment group and model group. Conclusion This study demonstrates that SF can increase bone mass and im-prove bone structure,which may be related to the im-provement of bone formation. SF is effective for GIOP in rats.

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