1.Mechanism of action of thymic stromal lymphopoietin in a mouse model of acetaminophen-induced acute liver injury
Wenshang CHEN ; Mingjing YIN ; Jijin ZHU
Journal of Clinical Hepatology 2025;41(1):110-117
ObjectiveTo investigate the role and mechanism of thymic stromal lymphopoietin (TSLP) in a mouse model of acetaminophen (APAP)-induced acute liver injury. MethodsA total of 16 wild-type (WT) male C57BL/6J mice were randomly divided into control group and APAP group, with 8 mice in each group, and the mice in the APAP group were given intraperitoneal injection of APAP solution at a dose of 400 mg/kg to establish an animal model, while those in the control group were given injection of an equal volume of normal saline, with samples collected after 6 hours. An automatic chemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); quantitative real-time PCR was used to measure the mRNA expression levels of the inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissue; the kit was used to measure the content of glutathione (GSH) in liver tissue homogenate; quantitative real-time PCR and Western blot were used to measure the transcriptional level and protein expression level of TSLP. Furthermore, 22 WT male C57BL/6J mice were randomly divided into control group with 8 mice, APAP group with 8 mice, and APAP+recombination TSLP (rTSLP) group with 6 mice; the mice in the APAP+rTSLP group were given intraperitoneal injection of rTSLP solution, while those in the control group and the APAP group were given injection of the solvent PBS; after 30 minutes, the mice in the APAP+rTSLP group and the APAP group were given injection of APAP solution, while those in the control group were given injection of an equal volume of normal saline. The serum levels of ALT and AST were measured; HE staining was used to observe the pathological changes of the liver; kits were used to measure the levels of the oxidative stress indices malondialdehyde (MDA) and superoxide dismutase (SOD) in liver tissue homogenate; Western blot was used to measure the expression levels of the autophagy-related proteins LC3Ⅰ/Ⅱ, Beclin1, and P62 and the molecules such as nuclear factor erythroid 2-related factor 2 (Nrf2), protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR). In addition, 16 WT male C57BL/6J mice and 16 TSLP receptor-silenced (TSLPR-/-) mice were divided into WT mouse control group, WT mouse APAP group, TSLPR-/- mouse control group, and TSLPR-/- mouse APAP group, with 8 mice in each group; the mice in the WT mouse APAP group and the TSLPR-/- mouse APAP group were used for modeling by intraperitoneal injection of APAP solution at a dose of 400 mg/kg, and those in the WT mouse control group and the TSLPR-/- mouse control group were given injection of an equal volume of normal saline. The serum levels of ALT and AST and the content of MDA in liver tissue were measured for these four groups, and Western blot was used to measure the protein expression levels of LC3Ⅰ/Ⅱ, Akt, and p-Akt. The independent-samples t test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsAfter the mouse model of APAP-induced acute liver injury was established successfully, there were significant increases in the mRNA and protein expression levels of TSLP compared with the control group (both P<0.01). In the study of rTSLP, compared with the control group, the APAP group had significant increases in ALT and AST (both P<0.001) and radial necrosis along the central vein observed by HE staining of liver tissue, as well as significant reductions in the protein expression levels of the oxidative stress indices SOD and Nrf2 and a significant increase in the level of MDA (all P<0.01); compared with the APAP group, the APAP+rTSLP group had significant reductions in ALT and AST, a significant reduction in necrotic area of liver tissue, significant increases in the protein expression levels of SOD and Nrf2, and a significant reduction in MDA (all P<0.05); there were significant differences in the protein expression levels of LC3Ⅰ/Ⅱ, Beclin1, P62, p-Akt, and p-mTOR between the APAP+rTSLP group and the control group (all P<0.01). In the study of TSLPR-/- mice, compared with the WT mice after modeling, the TSLPR-/- mice had significant increases in the levels of ALT, AST, and MDA and significant reductions in the expression levels of LC3Ⅰ/Ⅱ and p-Akt (all P<0.05). ConclusionTSLP can increase autophagy, reduce oxidative stress, and thus improve acute liver injury induced by APAP overdose, possibly by activating the PI3K/Akt signaling pathway and inhibiting mTOR.
2.Impacts of percutaneous endoscopic interlaminar discectomy on pain and lumbar function in patients with lumbar disc herniation
Liying CAO ; Mingjing JIANG ; Binzhen LIN ; Xiaofeng YIN ; Nan ZHONG ; Chunxiang CHEN ; Qinghua WU ; Kaiming CHEN
China Journal of Endoscopy 2025;31(3):46-52
Objective To investigate the impacts of percutaneous endoscopic interlaminar discectomy(PEID)on pain level and lumbar function in patients with lumbar disc herniation(LDH).Methods From January 2022 to August 2023,84 patients were diagnosed with L4/5 LDH based on clinical data and imaging information were selected as the study subjects.And they were assigned into 42 cases in experimental group and 42 cases in traditional groups complying with treatment methods.The traditional group underwent traditional open approach treatment,while the experimental group underwent PEID.The surgical indicators(including hospitalization time,surgical time,bed rest time,and intraoperative fluoroscopy frequency),the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were compared between the two groups,the visual analogue scale(VAS)score and Oswestry disability index(ODI)were used to quantify the pain level of waist and lower limbs and lumbar function,and the excellent and good rate of clinical satisfaction and the incidence of complications were compared.Results The hospitalization time and bed rest time of the experimental group were obviously shorter than those of the traditional group,while the fluoroscopy frequency was less than that of the traditional group,and surgical time was longer than that of the traditional group,the differences were statistically significant(P<0.05).After treatment,the pain VAS score and ODI of waist and lower limbs,the IL-6,and TNF-α in the two groups were lower than those before treatment,the experimental group was lower than the traditional group,the differences were statistically significant(P<0.05).The excellent and good rate of the experimental group and the traditional group were 88.10%and 83.33%,respectively,with no statistically significant difference(P>0.05).There was no statistically significant difference in the total incidence of complications between the two groups(P>0.05).Conclusion PEID surgery can effectively alleviate nerve compression,alleviate pain of waist and lower limbs,promote the recovering of lumbar function,and facilitate postoperative recovery in LDH patients.
3.Impacts of percutaneous endoscopic interlaminar discectomy on pain and lumbar function in patients with lumbar disc herniation
Liying CAO ; Mingjing JIANG ; Binzhen LIN ; Xiaofeng YIN ; Nan ZHONG ; Chunxiang CHEN ; Qinghua WU ; Kaiming CHEN
China Journal of Endoscopy 2025;31(3):46-52
Objective To investigate the impacts of percutaneous endoscopic interlaminar discectomy(PEID)on pain level and lumbar function in patients with lumbar disc herniation(LDH).Methods From January 2022 to August 2023,84 patients were diagnosed with L4/5 LDH based on clinical data and imaging information were selected as the study subjects.And they were assigned into 42 cases in experimental group and 42 cases in traditional groups complying with treatment methods.The traditional group underwent traditional open approach treatment,while the experimental group underwent PEID.The surgical indicators(including hospitalization time,surgical time,bed rest time,and intraoperative fluoroscopy frequency),the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were compared between the two groups,the visual analogue scale(VAS)score and Oswestry disability index(ODI)were used to quantify the pain level of waist and lower limbs and lumbar function,and the excellent and good rate of clinical satisfaction and the incidence of complications were compared.Results The hospitalization time and bed rest time of the experimental group were obviously shorter than those of the traditional group,while the fluoroscopy frequency was less than that of the traditional group,and surgical time was longer than that of the traditional group,the differences were statistically significant(P<0.05).After treatment,the pain VAS score and ODI of waist and lower limbs,the IL-6,and TNF-α in the two groups were lower than those before treatment,the experimental group was lower than the traditional group,the differences were statistically significant(P<0.05).The excellent and good rate of the experimental group and the traditional group were 88.10%and 83.33%,respectively,with no statistically significant difference(P>0.05).There was no statistically significant difference in the total incidence of complications between the two groups(P>0.05).Conclusion PEID surgery can effectively alleviate nerve compression,alleviate pain of waist and lower limbs,promote the recovering of lumbar function,and facilitate postoperative recovery in LDH patients.
4.Effect of lycopene preconditioning on TLRs/NF-κB signaling pathway during hypoxia-reoxygenation injury to rat cardiomyocytes
Mingjing YANG ; Weiwei LIU ; Wu YIN
Chinese Journal of Anesthesiology 2020;40(1):52-55
Objective:To evaluate the effect of lycopene preconditioning on Toll-like receptors (TLRs)/nuclear factor kappa B (NF-κB) signaling pathway during hypoxia-reoxygenation (H/R) injury to rat cardiomyocytes.Methods:The rat H9C2 cardiomyocytes were cultured in vitro, inoculated in a petri dish at a density of 8×10 4 cells/ml and divided into 3 groups( n=30 each) using a random number table method: control group (C group), H/R group and lycopene preconditioning group (LP group). The H9C2 cardiomyocytes were reoxygenated for 6 h after hypoxia to establish a model of H/R injury in H/R group and LP group.The cells were preconditioned with lycopene 20 μmol/L at 12 h before establishing the model in LP group.The cell viability was detected by CCK-8 assay.The cell apoptosis rate was detected by flow cytometry (Annexin V and PI double staining). The levels of lactic dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) and reactive oxygen species (ROS) were detected by microplate method.The expression of TLR2, TLR3 and NF-κB was detected by Western blot. Results:Compared with group C, the cell viability and SOD level were significantly decreased, the apoptosis rate and levels of LDH, MDA and ROS were increased, and the expression of TLR2, TLR3 and NF-κB was up-regulated in H/R and LP groups ( P<0.05). Compared with group H/R, the cell viability and SOD level were significantly increased, the apoptosis rate and levels of LDH, MDA and ROS were decreased, and the expression of TLR2, TLR3 and NF-κB was down-regulated in group LP ( P<0.05). Conclusion:The mechanism by which lycopene preconditioning attenuates H/R injury may be related to inhibiting activation of TLRs/NF-κB signaling pathway and inhibiting oxidative stress response in rat cardiomyocytes.

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