1.α-ketoglutarate ameliorated arsenic-induced hepatic lipid deposition in offspring via PI3K/AKT signaling pathway
Shuangrui BAO ; Hongyan WU ; Ying SUN ; Tong ZHAN ; Qian YANG ; Xinru LIANG ; Zhiyan WAN ; Wenyi CHEN ; Cheng ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(2):225-231
ObjectiveTo investigate the protective effect of α-ketoglutarate (α-KG) on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research (ICR) mice were mated in a ratio of 2∶1 between females and males, and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups: control group, arsenic group, α-KG group, arsenic+α-KG group. On gestational day 0-16 (GD0-GD16), the arsenic and arsenic+α-KG groups were exposed to sodium arsenite (NaAsO2 ,15 mg/L) in drinking water everyday, and the α-KG and arsenic+α-KG groups were gavaged with α-KG (2 g/kg) everyday. On GD16, pregnant mice were euthanized to collect fetal liver, and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides (TGs) and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction (qPCR) was used to detect the expression level of genes related to lipid synthesis, transport, and degradation, and phosphatidylinositol 3' -kinase/ protein kinase B (PI3K/AKT) in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver; body weight and crown-rump length were reduced (PTuKey<0.05); the level of hepatic TGs was elevated in arsenic group (PTuKey<0.05); oil-red O staining showed a significant increase in lipid droplets in arsenic group (PTuKey<0.01); the expression of lipid synthesis-related genes were significantly upregulated (PTuKey<0.05); the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated (PTuKey<0.05); the expression of PI3K, AKT decreased(PTuKey<0.05). Compared with the arsenic group, the body weight and crown-rump length of fetus increased in the arsenic+α-KG group (PTuKey<0.05); the level of hepatic TGs decreased in the arsenic+α-KG group (PTuKey<0.05); oil red O staining showed lipid droplets significantly decreased (PTuKey<0.01); the expression of lipid synthesis-related genes were downregulated (PTuKey<0.05), the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated (PTuKey<0.05); the expression levels of PI3K and AKT increased (PTuKey<0.05). Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.
2.4-Phenylbutyrate ameliorates lipopolysaccharide-induced bile acid metabolism disorder in maternal mice
Xinru LIANG ; Ying SUN ; Shuangrui BAO ; Tong ZHAN ; Hongyan WU ; Wenkang TAO ; Lun ZHANG ; Jianqing WANG ; Cheng ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(7):1183-1190
ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA) on bile acid metabolism disorders induced by bacterial lipopolysaccharide (LPS) in late-pregnant mice, and to clarify the regulatory mechanism of endoplasmic reticulum stress (ERS) in intrahepatic cholestasis of pregnancy (ICP). MethodsTwenty-four pregnant mice were divided into control group, LPS group, 4-PBA group, and LPS+4-PBA group. On the 16th day of pregnancy, the LPS group received intraperitoneal injection of LPS (200 μg/kg) and the 4-PBA group received injection of 4-PBA (150 mg/kg). In the LPS+4-PBA group, 4-PBA was intraperitoneally injected first, followed by LPS administration 1 h later. Serum total bile acid (TBA), liver injury markers, bile acid profiles, and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice(P<0.05), activated ERS markers and inflammatory factors, and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1(all P<0.05). 4-PBA intervention effectively inhibited ERS, reduced TBA levels(P<0.05), and upregulated Ntcp, Bsep, Mdr3, and Mrp3 gene expression(all P<0.05). ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters, providing a theoretical basis for targeted therapy of ICP.
3.Galectin 3 regulates silica-induced pulmonary fibrosis in mice via MAPK signalling pathway
Xinbei ZHOU ; Xiaohan JIANG ; Ningjuan LIANG ; Xinru TU
Journal of Environmental and Occupational Medicine 2026;43(8):1027-1031
Background Silicosis is a progressive pulmonary fibrotic disease caused by long-term inhalation of silica (SiO2) dust, and abnormal fibroblast activation is a central pathological mechanism. Galectin 3 (LGALS3) plays a significant role in fibrosis across multiple organs; however, its specific molecular mechanism in SiO2-induced pulmonary fibrosis remains unclear. Objective To investigate the role of LGALS3 in silica (SiO2) induced pulmonary fibrosis and its potential molecular mechanisms. Methods Differentially expressed genes in mouse lung fibroblasts treated with SiO2 for 56 d were analysed using the GSE183682 single-cell RNA sequencing dataset, followed by pathway enrichment analysis. A mouse model of pulmonary fibrosis was established by intratracheal instillation of SiO2 suspension (50 mg·mL−1, 100 μL). Lung index, hydroxyproline content, and histopathological changes (HE staining) were assessed. Western blot and immunofluorescence staining were used to evaluate the expression of LGALS3, MAPK pathway proteins, and fibrosis markers [collagen type I alpha 1 chain (COL1A1) and α-smooth muscle actin (ACTA2)]. Results Single-cell RNA sequencing analysis identified 53 differentially expressed genes in fibroblasts, and Lgals3 was significantly upregulated in the SiO2 group. SiO2 exposure successfully induced pulmonary fibrosis in mice, as indicated by weight loss, elevated hydroxyproline content, alveolar structural disruption, and collagen deposition. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that Lgals3-associated genes were enriched in Toll-like receptor/chemokine signaling pathways. After SiO2 exposure, LGALS3 expression was increased in fibrotic lung tissue and co-localized with ACTA2, an activated fibroblast and myofibroblast marker. This was accompanied by activation of the MAPK signaling pathway. Conclusion LGALS3 may be involved in fibroblast activation and collagen deposition, potentially through activation of the MAPK signalling pathway. These findings suggest that LGALS3 may represent a potential regulatory target in SiO2-induced pulmonary fibrosis.
4.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.
5.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.
6.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.
7.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.
8.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.
9.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.
10.Analysis of Influencing Factors and Mechanism Model of Defensive Medicine based on Grounded Theory
Xinle YIN ; Huanyu ZHANG ; Juan ZHAO ; Chen WANG ; Yajie FENG ; Xinru LIU ; Yue ZHOU ; Libo LIANG
Chinese Hospital Management 2024;44(7):6-10,15
Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

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