1.Serotype and drug resistance of Salmonella from foodborne diseases in Longwan District
ZHOU Shanhui ; HU Yuqin ; ZHENG Qiongqiong ; WANG Xiaohong ; LI Yi ; XIANG Guangxin
Journal of Preventive Medicine 2025;37(7):697-700,704
Objective:
To analyze the serotypes and drug resistance of Salmonella isolated from food-borne disease surveillance samples in Longwan District, Wenzhou City, Zhejiang Province, so as to provide evidence for the prevention and treatment of Salmonella infection.
Methods:
Salmonella strains isolated from feces or anal swabs of patients with foodborne diarrhea in Longwan District People's Hospital from 2018 to 2024 were collected. After re-identification, slide agglutination test was used to identify serotypes. The drug susceptibility test of live Salmonella strains was performed using the broth microdilution method, and the resistance patterns were analyzed.
Results:
A total of 2 293 samples were collected, and 186 strains of Salmonella were isolated, with a detection rate of 8.11%. The detection rate was higher from May to October. A total of 28 Salmonella serotypes were identified, with S. typhimurium (72 isolates, 38.71%), S. enteritidis (31 isolates, 16.67%), and S. London (30 isolates, 16.13%) being dominant. Among the 121 Salmonella live strains, 20 strains were susceptible to 14 antibacterial drugs. A total of 101 strains were resistant to antibacterial drugs, and the drug resistance rate was 1.65%-67.77%, with the drug resistance rate of ampicillin being the highest, and the drug resistance rate of imipenem was the lowest. S. typhimurium had the highest resistance rate to tetracycline (78.26%). S. enteritidis had the highest resistance rate to ampicillin (100.00%). S. London had the highest resistance rate to tetracycline (66.67%). Fifty-five types of drug resistance patterns were detected, showing a number of drug resistance of 1-10, of which 76 strains were multi-drug resistant, accounting for 75.25%. The predominant multidrug resistance patterns were ampicillin/sulbactam-cefazolin-ampicillin-nalidixic acid (10.53%), tetracycline-ampicillin-nalidixic acid (9.21%), and ampicillin/sulbactam-ampicillin-nalidixic acid (7.89%).
Conclusions
Salmonella strains isolated from foodborne diseases in Longwan District were mainly detected in summer and autumn. S. typhimurium, S. enteritidis, and S. London were the predominant serotypes. The drug resistance of Salmonella to different antibacterial drugs was different, and the drug resistance spectrum showed diversity.
2.Mechanism of Wenyang Jieyu Prescription in Regulating Activation of Mouse Hippocampal Microglia Based on JAK2/STAT3 Signaling Pathway
Ying WANG ; Zihan GONG ; Wenqing LIANG ; Jingwen YANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):88-96
ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth, the rats were randomly divided into blank (NC) group, maternal-infant separation (MS) group, restraint stress (RS) group, maternal-infant separation combined with restraint stress (MRS) group, Wenyang group, Jieyu group, Wenyang Jieyu (XSF) group, and minocycline group. Maternal-infant separation was performed on day 5 (PD5), followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group, Xiaoyao group, XSF group and minocycline group were 5.85, 12.03, 16.71 g·kg-1 and 50 mg·kg-1, respectively. Restraint stress was applied on PD90. The model was evaluated using glucose, social interaction, open field, and O-maze behavior tests, as well as high-performance liquid chromatography to measure serotonin, dopamine, and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 (Iba-1) protein, a marker of hippocampal microglia, was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of M1 markers, JAK2/STAT3 pathway-related genes, and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group, the MRS group exhibited depression-like behavior, with significantly decreased levels of neurotransmitters in the hippocampus (P<0.05, P<0.01), increased expression of Iba-1 (P<0.01), and elevated protein levels of JAK2 and STAT3 (P<0.05). The mRNA expression levels of CD68, CD11b, IL-1β, JAK2, and STAT3 were significantly increased (P<0.01), while IL-10 mRNA expression was significantly decreased (P<0.01). Compared with the MRS group, the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups, the hippocampal neurotransmitter content was significantly increased (P<0.05, P<0.01), and Iba-1 expression was significantly decreased (P<0.01). The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68, CD11b, JAK2, STAT3, and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups (P<0.05, P<0.01), while IL-10 mRNA expression was significantly increased (P<0.05, P<0.01). ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.
3.Correlation between serum levels of HAMP, SPP1, RGS2 and clinical pathological characteristics of gastric cancer patients and their predictive value for postoperative recurrence or metastasis
Guangxin LI ; Huijuan QUAN ; Zhijuan GAO ; Xiaojun WANG ; Liang LI ; Qian DONG ; Yongtao MIAO ; Dongsheng LIU
Journal of International Oncology 2025;52(8):502-507
Objective:To explore the correlation between serum hepcidin antimicrobial peptide (HAMP), secreted phosphoprotein 1 (SPP1), and regulator of G protein signaling 2 (RGS2) levels and the clinical pathological characteristics of gastric cancer patients, and their predictive value for postoperative recurrence or metastasis.Methods:A total of 92 gastric cancer patients treated at Handan First Hospital from March 2021 to March 2023 were selected as the gastric cancer group, and 92 healthy individuals who underwent physical examinations during the same period were selected as the control group. The serum levels of HAMP, SPP1 and RGS2 were compared between the two groups. According to the mean levels of HAMP, SPP1, and RGS2 in the serum of gastric cancer patients, they were divided into HAMP high level group and HAMP low level group, SPP1 high level group and SPP1 low level group, RGS2 high level group and RGS2 low level group. The clinicopathological characteristics of gastric cancer patients with different levels of HAMP, SPP1 and RGS2 were compared respectively. After a median follow-up of 18 months, gastric cancer patients were divided into a non-recurrence or metastasis group ( n=59) and a recurrence and metastasis group ( n=33) based on whether the tumor recurred or metastasized. The serum levels of HAMP, SPP1, and RGS2 were compared between the two groups of patients. The predictive value of HAMP, SPP1 and RGS2 for postoperative recurrence or metastasis in patients with gastric cancer was analyzed by using the receiver operator characteristic (ROC) curve. Results:Compared with the control group, the gastric cancer group had higher levels of serum HAMP [ (52.28±5.44) ng/ml vs. (31.22±4.18) ng/ml] and SPP1 [ (55.96±6.43) ng/ml vs. (36.99±5.25) ng/ml] ( t=29.44, P<0.001; t=21.92, P<0.001), and lower level of RGS2 [ (3.72±0.66) mg/L vs. (5.11±0.87) mg/L) ] ( t=12.21, P<0.001). There were statistically significant differences in maximum tumor diameter ( χ2=13.07, P<0.001; χ2=6.71, P=0.010; χ2=10.56, P=0.001), TNM staging ( χ2=7.42, P=0.006; χ2=6.36, P=0.012; χ2=5.39, P=0.020), lymph node metastasis ( χ2=23.41, P<0.001; χ2=6.52, P=0.011; χ2=13.11, P<0.001), and differentiation degree ( χ2=9.01, P=0.003; χ2=7.97, P=0.005; χ2=15.29, P<0.001) between the gastric cancer patients in the HAMP high level group ( n=44) and the HAMP low level group ( n=48), the SPP1 high level group ( n=43) and the SPP1 low level group ( n=49), and the RGS2 high level group ( n=50) and the RGS2 low level group ( n=42). Compared with the non-recurrence or metastatic group, the recurrence and metastatic group had higher levels of serum HAMP [ (59.26±5.66) ng/ml vs. (48.37±4.28) ng/ml] and SPP1 [ (62.85±6.36) ng/ml vs. (52.11±5.38) ng/ml] level ( t=10.40, P<0.001; t=8.60, P<0.001), and lower level of RGS2 [ (3.01±0.48) mg/L vs. (4.12±0.69) mg/L] ( t=8.19, P<0.001). ROC curve analysis showed that the area under the curve (AUC) values of serum HAMP, SPP1, and RGS2 levels alone for predicting postoperative recurrence or metastasis in gastric cancer patients were 0.777, 0.813, and 0.778, respectively. The AUC value of the combination of the three indicators for predicting postoperative recurrence or metastasis in gastric cancer patients was 0.871. The predictive efficacy of the combination of the three indicators for predicting postoperative recurrence or metastasis in gastric cancer patients was better than that alone ( Z=2.51, P=0.035; Z=2.61, P=0.032; Z=2.71, P=0.029) . Conclusions:The levels of HAMP and SPP1 in the serum of gastric cancer patients increase, while the level of RGS2 decreases, and the levels of the three are related to the maximum tumor diameter, TNM staging, lymph node metastasis and differentiation degree, and their combined detection has higher predictive value for postoperative recurrence or metastasis in gastric cancer patients.
4.Research progress on applications for the mouse brain atlas and its analysis techniques
Mingmin PAN ; Qiyang WANG ; Guangxin YUE
Acta Laboratorium Animalis Scientia Sinica 2025;33(7):1053-1063
Mice are a core model organism in neuroscience and are undergoing a technological transition in whole-brain atlas construction,as researchers shift from traditional anatomical approaches to multidimensional molecular-level analysis.This marks a new phase in brain research method ology,characterized by higher resolution and systemic integration.Spatial transcriptomics technologies have significantly advanced the biological depth of neuroscience studies,offering novel paradigms for exploring dynamic neural circuit evolution and cellular diversity in the brain.By combining traditional anatomical localization,single-cell molecular connectomics,and functional imaging for macroscopic dynamic tracking,brain atlas research achieves"molecule-circuit-behavior"tri-level integration,thereby constructing molecular regulatory networks underlying dynamic neural circuit remodeling.However,current challenges persist in technical integration.Reference brain atlases hold great promise for elucidating brain homeostasis mechanisms,identifying abnormal circuit metabolic features in neurological disorders(e.g.,anxiety),and screening therapeutic targets.Future brain atlas research must advance multimodal technology fusion and cross-dimensional data integration to achieve precise mapping from static structures to dynamic functional networks,and thus provide revolutionary tools for neuroscience.
5.Effects of exosomes secreted from mesenchymal stem cells on chondrocyte injury under hypoxia
Shaochu CHEN ; Ming GONG ; Wang ZHANG ; Jiawen WU ; Guangxin HUANG ; Yadong ZHANG
The Journal of Practical Medicine 2025;41(22):3529-3536
Objective To investigate the effects of exosomes derived from hypoxia-treated mesenchymal stem cells on chondrocyte injury.Methods After mesenchymal stem cells were subjected to hypoxic treatment,the secreted exosomes were collected and co-cultured with IL-1β-stimulated chondrocytes.Cell viability was assessed using the CCK-8 assay,while apoptosis was evaluated by flow cytometry and the measurement of Caspase-3 and PARP activities.Intracellular levels of ROS,Fe2+,and MDA were quantified using commercial assay kits.The expression of GPX4,SLC7A11,and ACSL4 was analyzed at both mRNA and protein levels via qRT-PCR and Western blot,respectively.Additionally,the secretion of COL2A1,MMP13,ADAMTS5,TNF-α,IL-6,and PGE2 was determined by ELISA.Results Chondrocyte viability was significantly enhanced following the uptake of exosomes derived from hypoxia-treated mesenchymal stem cells(H-Exo)(P<0.05).IL-1β treatment reduced chondrocyte viability,increased Caspase-3 and PARP activities,and promoted apoptosis(P<0.05);however,H-Exo effectively reversed IL-1 β-induced apoptotic effects.Furthermore,IL-1 β markedly down-regulated the expression of GPX4 and SLC7A11,up-regulated ACSL4 expression,and elevated intracellular levels of ROS,Fe2+,and MDA(P<0.05),indicating the induction of ferroptosis.Both the ferroptosis inhibitor and H-Exo significantly attenuated IL-1β-triggered ferroptosis,and H-Exo counteracted the detrimental effects of IL-1β as well as those induced by a ferroptosis inducer.Additionally,IL-1β suppressed the expression of the chondrogenic marker COL2A1,up-regulated the catabolic enzymes MMP13 and ADAMTS5,and enhanced the secretion of pro-inflammatory cyto-kines TNF-α,IL-6,and PGE2(P<0.05).Notably,H-Exo alleviated IL-1β-mediated inflammation and restored the balance between chondrogenic anabolism and catabolism.Conclusions Exosomes secreted by mesenchymal stem cells under hypoxic conditions can effectively inhibit chondrocyte apoptosis and ferroptosis,thereby alleviating cellular injury.These findings suggest that such exosomes exert a protective effect on chondrocytes and hold prom-ise as a novel therapeutic strategy for cartilage repair.
6.Effects of LncRNA MAGI2-AS3 on the migration,invasion,and epithelial mesenchymal transition of gastric cancer cells by regulating the miR-194-5p/CAV1 axis
Guangxin LI ; Huijuan QUAN ; Zhijuan GAO ; Xiaojun WANG ; Liang LI ; Yuqing CAO ; Dongsheng LIU
Journal of Clinical Surgery 2025;33(9):974-980
Objective To investigate the effects of long non coding RNA MAGI2 antisense chain RNA3(LncRNA MAGI2-AS3)on the migration,invasion,and epithelial mesenchymal transition(EMT)of gastric cancer(GCa)cells by regulating the miR-194-5 p/caveolin-1(CAV1)axis.Methods Fifty-two GCa patients who underwent surgical resection in our hospital from August 2022 to December 2023 were selected.Cancer and adjacent tissues were collected,and AGS,MKN45,HGC-27,and GES1 cells were cultured in vitro.The expression of MAGI2-AS3,miR-194-5p,and CAV1 in tissue samples and cell lines was analyzed.AGS cells were randomly separated into AGS group,sh-AGS group sh-MAGI2-AS3 group,miR-NC group,and in miR-194-5p group.The proliferation,apoptosis,migration,and invasion of cells in each group were compared.Immunoblotting was applied to analyze the expression of E-cadherin,CAV1,proliferating cell nuclear antigen(PCNA),N-cadherin,Bax,matrix metalloproteinase 2(MMP2),and vimentin of cells in each group.Dual luciferase assay was applied to analyze the relationship between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Results The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and positive expression rate of CAV1 protein in GCa tissue increased,while the expression of miR-194-5p mRNA decreased(P<0.05).The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and CAV1 protein in HGC-27,MKN45,and AGS cells was higher than that of GES1 cells,the expression of miR-194-5p mRNA was lower than that of GES1 cells(P<0.05).Compared with the AGS and sh-AGS groups,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in sh-MAGI2-AS3 group decreased,the apoptosis rate,expression of E-cadherin,and Bax increased(P<0.05).Compared with the miR-NC group and sh-MAGI2-AS3 group,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in in-miR-194-5p group increased,the apoptosis rate,expression of E-cadherin,and Bax reduced(P<0.05).ENCORI database found that there were multiple binding sites between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Compared with the WT-MAGI2-AS3+miR-NC group,the luciferase activity in the WT-MAGI2-AS3+miR-194-5p group decreased(P<0.05),while compared with the WT-CAV1+miR-NC group,the luciferase activity in the WT-CAV1+miR-194-5p group decreased(P<0.05).Conclusion LncRNA MAGI2-AS3 silencing can target miR-194-5p to downregulate CAV1,thereby inhibiting GCa cell migration,invasion,and EMT.
7.Epidemic characteristics of 192 patients with Hashimoto's thyroiditis and clinical symptoms
Jingli FAN ; Tiefeng SUN ; Jingtao WANG ; Jing WANG ; Guangxin WEI ; Yanan CUI ; Hongxu GAO
Chinese Journal of Endemiology 2025;44(10):846-850
Objective:To study the epidemic characteristics and clinical symptoms of patients with Hashimoto's thyroiditis (HT) in Shandong Province, and to provide a basis for further optimizing the clinical treatment strategies for HT.Methods:Data on HT patients admitted to Shandong Provincial Center for Disease Control and Prevention from January 2018 to December 2023 were collected. A retrospective analysis was conducted to analyze their epidemiological characteristics, clinical symptoms, and auxiliary examination results.Results:A total of 192 HT patients' data were included, comprising 42 males (21.87%) and 150 females (78.13%). The average age of patients was 40.38 years old, ranging from 9 to 74 years old. Most patients resided in urban areas (129 cases, 67.19%). HT cases occurred throughout the year in every mouth, with higher incidence in June (32 cases, 16.7%) and July (20 cases, 10.4%), lower incidence in March (8 cases, 4.2%) and April (10 cases, 5.2%), and sporadic cases in other months. Based on clinical manifestations, among all HT patients, there were 66 cases (34.38%) of Hashitoxicosis type, 11 cases (5.73%) of pseudothyrotoxicosis type, 7 cases (3.65%) of exophthalmic type, 5 cases (2.60%) of subacute thyroiditis-like type, 3 cases (1.56%) of juvenile type, 35 cases (18.23%) of fibrous type, 39 cases (20.31%) of thyroid adenoma or carcinoma type, and 26 cases (13.54%) of other autoimmune diseases type. Based on disease progression, among all HT patients, there were 61 cases (31.77%) in the hyperthyroid phase, 16 cases (8.33%) in the hyperthyroid-hypothyroid coexisting phase, and 115 cases (59.90%) in the hypothyroid phase. Based on clinical symptoms, among all HT patients,there were 78 cases(40.62%) of neck mass symptoms, 101 cases (52.60%) of digestive system symptoms, and 95 cases (49.48%) of low metabolic symptoms. Laboratory tests revealed that 144 cases had elevated levels of both thyroglobulin antibody and thyroid peroxidase antibody. Color ultrasound examination showed strip-like echoes in the thyroid in 99 cases (51.56%) and grid-like echoes in 43 cases (22.40%). After treatment with antithyroid drugs or appropriate thyroid hormone supplementation, all 192 HT patients experienced symptom relief.Conclusions:HT patients in Shandong Province were predominantly female and urban residents. Common clinical symptoms included anterior neck swelling, constipation, fever, and weight gain. Early detection, diagnosis, and treatment could delay disease progression.
8.Effects of LncRNA MAGI2-AS3 on the migration,invasion,and epithelial mesenchymal transition of gastric cancer cells by regulating the miR-194-5p/CAV1 axis
Guangxin LI ; Huijuan QUAN ; Zhijuan GAO ; Xiaojun WANG ; Liang LI ; Yuqing CAO ; Dongsheng LIU
Journal of Clinical Surgery 2025;33(9):974-980
Objective To investigate the effects of long non coding RNA MAGI2 antisense chain RNA3(LncRNA MAGI2-AS3)on the migration,invasion,and epithelial mesenchymal transition(EMT)of gastric cancer(GCa)cells by regulating the miR-194-5 p/caveolin-1(CAV1)axis.Methods Fifty-two GCa patients who underwent surgical resection in our hospital from August 2022 to December 2023 were selected.Cancer and adjacent tissues were collected,and AGS,MKN45,HGC-27,and GES1 cells were cultured in vitro.The expression of MAGI2-AS3,miR-194-5p,and CAV1 in tissue samples and cell lines was analyzed.AGS cells were randomly separated into AGS group,sh-AGS group sh-MAGI2-AS3 group,miR-NC group,and in miR-194-5p group.The proliferation,apoptosis,migration,and invasion of cells in each group were compared.Immunoblotting was applied to analyze the expression of E-cadherin,CAV1,proliferating cell nuclear antigen(PCNA),N-cadherin,Bax,matrix metalloproteinase 2(MMP2),and vimentin of cells in each group.Dual luciferase assay was applied to analyze the relationship between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Results The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and positive expression rate of CAV1 protein in GCa tissue increased,while the expression of miR-194-5p mRNA decreased(P<0.05).The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and CAV1 protein in HGC-27,MKN45,and AGS cells was higher than that of GES1 cells,the expression of miR-194-5p mRNA was lower than that of GES1 cells(P<0.05).Compared with the AGS and sh-AGS groups,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in sh-MAGI2-AS3 group decreased,the apoptosis rate,expression of E-cadherin,and Bax increased(P<0.05).Compared with the miR-NC group and sh-MAGI2-AS3 group,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in in-miR-194-5p group increased,the apoptosis rate,expression of E-cadherin,and Bax reduced(P<0.05).ENCORI database found that there were multiple binding sites between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Compared with the WT-MAGI2-AS3+miR-NC group,the luciferase activity in the WT-MAGI2-AS3+miR-194-5p group decreased(P<0.05),while compared with the WT-CAV1+miR-NC group,the luciferase activity in the WT-CAV1+miR-194-5p group decreased(P<0.05).Conclusion LncRNA MAGI2-AS3 silencing can target miR-194-5p to downregulate CAV1,thereby inhibiting GCa cell migration,invasion,and EMT.
9.Research progress on applications for the mouse brain atlas and its analysis techniques
Mingmin PAN ; Qiyang WANG ; Guangxin YUE
Acta Laboratorium Animalis Scientia Sinica 2025;33(7):1053-1063
Mice are a core model organism in neuroscience and are undergoing a technological transition in whole-brain atlas construction,as researchers shift from traditional anatomical approaches to multidimensional molecular-level analysis.This marks a new phase in brain research method ology,characterized by higher resolution and systemic integration.Spatial transcriptomics technologies have significantly advanced the biological depth of neuroscience studies,offering novel paradigms for exploring dynamic neural circuit evolution and cellular diversity in the brain.By combining traditional anatomical localization,single-cell molecular connectomics,and functional imaging for macroscopic dynamic tracking,brain atlas research achieves"molecule-circuit-behavior"tri-level integration,thereby constructing molecular regulatory networks underlying dynamic neural circuit remodeling.However,current challenges persist in technical integration.Reference brain atlases hold great promise for elucidating brain homeostasis mechanisms,identifying abnormal circuit metabolic features in neurological disorders(e.g.,anxiety),and screening therapeutic targets.Future brain atlas research must advance multimodal technology fusion and cross-dimensional data integration to achieve precise mapping from static structures to dynamic functional networks,and thus provide revolutionary tools for neuroscience.
10.Effects of exosomes secreted from mesenchymal stem cells on chondrocyte injury under hypoxia
Shaochu CHEN ; Ming GONG ; Wang ZHANG ; Jiawen WU ; Guangxin HUANG ; Yadong ZHANG
The Journal of Practical Medicine 2025;41(22):3529-3536
Objective To investigate the effects of exosomes derived from hypoxia-treated mesenchymal stem cells on chondrocyte injury.Methods After mesenchymal stem cells were subjected to hypoxic treatment,the secreted exosomes were collected and co-cultured with IL-1β-stimulated chondrocytes.Cell viability was assessed using the CCK-8 assay,while apoptosis was evaluated by flow cytometry and the measurement of Caspase-3 and PARP activities.Intracellular levels of ROS,Fe2+,and MDA were quantified using commercial assay kits.The expression of GPX4,SLC7A11,and ACSL4 was analyzed at both mRNA and protein levels via qRT-PCR and Western blot,respectively.Additionally,the secretion of COL2A1,MMP13,ADAMTS5,TNF-α,IL-6,and PGE2 was determined by ELISA.Results Chondrocyte viability was significantly enhanced following the uptake of exosomes derived from hypoxia-treated mesenchymal stem cells(H-Exo)(P<0.05).IL-1β treatment reduced chondrocyte viability,increased Caspase-3 and PARP activities,and promoted apoptosis(P<0.05);however,H-Exo effectively reversed IL-1 β-induced apoptotic effects.Furthermore,IL-1 β markedly down-regulated the expression of GPX4 and SLC7A11,up-regulated ACSL4 expression,and elevated intracellular levels of ROS,Fe2+,and MDA(P<0.05),indicating the induction of ferroptosis.Both the ferroptosis inhibitor and H-Exo significantly attenuated IL-1β-triggered ferroptosis,and H-Exo counteracted the detrimental effects of IL-1β as well as those induced by a ferroptosis inducer.Additionally,IL-1β suppressed the expression of the chondrogenic marker COL2A1,up-regulated the catabolic enzymes MMP13 and ADAMTS5,and enhanced the secretion of pro-inflammatory cyto-kines TNF-α,IL-6,and PGE2(P<0.05).Notably,H-Exo alleviated IL-1β-mediated inflammation and restored the balance between chondrogenic anabolism and catabolism.Conclusions Exosomes secreted by mesenchymal stem cells under hypoxic conditions can effectively inhibit chondrocyte apoptosis and ferroptosis,thereby alleviating cellular injury.These findings suggest that such exosomes exert a protective effect on chondrocytes and hold prom-ise as a novel therapeutic strategy for cartilage repair.


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