1.Development of a predictive model and application for spontaneous passage of common bile duct stones based on automated machine learning
Jian CHEN ; Kaijian XIA ; Fuli GAO ; Luojie LIU ; Ganhong WANG ; Xiaodan XU
Journal of Clinical Hepatology 2025;41(3):518-527
ObjectiveTo develop a predictive model and application for spontaneous passage of common bile duct stones using automated machine learning algorithms given the complexity of treatment decision-making for patients with common bile duct stones, and to reduce unnecessary endoscopic retrograde cholangiopancreatography (ERCP) procedures. MethodsA retrospective analysis was performed for the data of 835 patients who were scheduled for ERCP after a confirmed diagnosis of common bile duct stones based on imaging techniques in Changshu First People’s Hospital (dataset 1) and Changshu Traditional Chinese Medicine Hospital (dataset 2). The dataset 1 was used for the training and internal validation of the machine learning model and the development of an application, and the dataset 2 was used for external testing. A total of 22 potential predictive variables were included for the establishment and internal validation of the LASSO regression model and various automated machine learning models. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were used to assess the performance of models and identify the best model. Feature importance plots, force plots, and SHAP plots were used to interpret the model. The Python Dash library and the best model were used to develop a web application, and external testing was conducted using the dataset 2. The Kolmogorov-Smirnov test was used to examine whether the data were normally distributed, and the Mann-Whitney U test was used for comparison between two groups, while the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsAmong the 835 patients included in the study, 152 (18.20%) experienced spontaneous stone passage. The LASSO model achieved an AUC of 0.875 in the training set (n=588) and 0.864 in the validation set (n=171), and the top five predictive factors in terms of importance were solitary common bile duct stones, non-dilated common bile duct, diameter of common bile duct stones, a reduction in serum alkaline phosphatase (ALP), and a reduction in gamma-glutamyl transpeptidase (GGT). A total of 55 models were established using automated machine learning, among which the gradient boosting machine (GBM) model had the best performance, with an AUC of 0.891 (95% confidence interval: 0.859 — 0.927), outperforming the extreme randomized tree mode, the deep learning model, the generalized linear model, and the distributed random forest model. The GBM model had an accuracy of 0.855, a sensitivity of 0.846, and a specificity of 0.857 in the test set (n=76). The variable importance analysis showed that five factors had important influence on the prediction of spontaneous stone passage, i.e., were solitary common bile duct stones, non-dilated common bile duct, a stone diameter of <8 mm, a reduction in serum ALP, and a reduction in GGT. The SHAP analysis of the GBM model showed a significant increase in the probability of spontaneous stone passage in patients with solitary common bile duct stones, non-dilated common bile duct, a stone diameter of <8 mm, and a reduction in serum ALP or GGT. ConclusionThe GBM model and application developed using automated machine learning algorithms exhibit excellent predictive performance and user-friendliness in predicting spontaneous stone passage in patients with common bile duct stones. This application can help avoid unnecessary ERCP procedures, thereby reducing surgical risks and healthcare costs.
2.Effects of long working hours and shift work on the mental health of community medical workers
Xiaodan YANG ; Danni LI ; Jicui CHEN ; Jiayi WANG ; Zou CHEN
China Occupational Medicine 2025;52(3):282-287
Objective To explore the association of working hours and shift work with occupational stress, fatigue accumulation, and depressive symptoms among primary community medical workers. Methods A total of 516 medical workers from five community medical service centers in Pudong New Area, Shanghai City, were selected as the research subjects using the convenience sampling method. The Core Scale of Occupational Stress Measurement, the Workers' Fatigue Accumulation Self-diagnosis Questionnaire, and the Patient Health Questionnaire were used to assess research subjects' occupational stress, fatigue accumulation, and depressive symptoms, respectively. Results Long working hours (>40 hours/week) were reported by 50.4% of workers among the research subjects, while shift works were reported by 16.9% of the workers. The detection rates of occupational stress, fatigue accumulation, and depressive symptoms were 26.6%, 41.7%, and 30.8%, respectively. Multivariate logistic regression analysis result revealed that, after adjusting for confounders such as age, sex, and education level, longer working hours were associated with higher risks of occupational stress, fatigue accumulation, and depressive symptoms (all P<0.05). Shift workers in community medical centers had higher risks of occupational stress, fatigue accumulation, and depressive symptoms compared with non-shift workers (all P<0.05). Conclusion Long working hours and shift work could increase the risks of occupational stress, fatigue accumulation, and depressive symptoms among community medical workers.
3.Regulation of natural killer cell subtypes and functions by programmed cell death protein 1 and its receptor at the maternal-fetal interface in mice infected with Toxoplasma gondii during the second trimester
Jiayue SUN ; Qiuhua BAI ; Xiaodan CHEN ; Jiayin LÜ ; Shanshan HE ; Lili TANG ; Dejun LIAO ; Dengyu LIU ; Xiaoyin FU
Chinese Journal of Schistosomiasis Control 2025;37(5):465-474
Objective To investigate the regulatory role of the programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein ligand 1 (PD-L1) signaling on the subtypes and functions of natural killer (NK) cells at the maternal-fetal interface during the second trimester in mice following Toxoplasma gondii infection during the first trimester. Methods Twelve 6- to 8-week-old female mice of the C57BL/6J strain were divided into a control group and an infection group, of 6 mice in each group. On the 6.5th day of pregnancy (Gd6.5), each pregnant mouse in the infection group was intraperitoneally injected with 150 tachyzoites of the Toxoplasma gondii PRU strain, while mice in the control group were injected with an equal volume of physiological saline. On the 12.5th day of pregnancy (Gd12.5), uterus and placenta tissues were sampled from pregnant mice for pathological observations, and the mRNA expression levels of PD-1, PD-L1, and tumor necrosis factor-α (TNF-α) were quantified in uterus and placenta tissues. The PD-1 and DX5 expression was measured on NK cells at the maternal-fetal interface using flow cytometry. In addition, the in vitro JEG-3 trophoblast cells and NK-92MI cells co-culture system was established as the control group, and the addition of T. gondii tachyzoites in the co-culture system served as the infection group. The PD-1, PD-L1, and DX5 mRNA expression was quantified in cells using real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) assay, and the TNF-α concentration was measured in the cell culture supernatant using enzyme-linked immunosorbent assay (ELISA). Results On Gd12.5, clear and intact cellular structures of placental decidual tissues were seen in pregnant mice in the control group, with no remarkable abnormal changes found in the uterine columnar epithelial cells, and inflammatory cell infiltration and blood stasis at varying degrees were found in uterine and placental tissues from pregnant mice in the infection group. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.004 ± 0.004), (1.001 ± 0.001), and (1.001 ± 0.001) in uterine tissues from pregnant mice in the control group and (2.480 ± 0.720), (3.355 ± 0.920), and (2.391 ± 0.073) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.007 ± 0.010), (1.006 ± 0.006), and (1.001 ± 0.001) in the uterine tissues in the control group and (6.948 ± 1.918), (3.225 ± 1.034), and (1.536 ± 0.150) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was higher in both the uterine (t = 3.55, 4.43 and 33.02, all P values < 0.05) and placental tissues (t = 5.36, 3.72 and 6.18, all P values < 0.05) in the infection group than in the control group. Flow cytometry showed that the proportions of PD-1+ NK cells, PD-1+ DX5+ NK cells, and DX5+ NK cells were (12.200 ± 1.082)%, (9.373 ± 7.728)%, and (44.000 ± 4.095)% in uterine tissues from pregnant mice in the control group, and (21.733 ± 1.630)%, (18.767 ± 1.242)%, and (73.367 ± 0.611)% in the infection group, respectively. The proportions of PD-1+ NK cells, PD-1+ DX5+ NK cells, and DX5+ NK cells were (1.100 ± 0.510)%, (2.277 ± 1.337)%, and (96.167 ± 2.831)% in placental tissues from mice in the control group, and (26.867 ± 9.722)%, (23.433 ± 6.983)%, and (82.467 ± 2.248)% in the infection group, respectively. The proportions of PD-1+ NK cells (t = 8.45, P < 0.05) and DX5+ NK cells (t = 12.29, P < 0.05) were higher in uterine tissues from pregnant mice in the infection group than in the control group, and no significant difference was seen in the proportion of PD-1+ DX5+ NK cells (Z = -1.09, P > 0.05). The proportions of PD-1+ NK cells (t = 4.58, P < 0.05) and PD-1+ DX5+ NK cells (t = 5.15, P < 0.05) were higher in placental tissues from pregnant mice in the infection group than in the control group, while the proportion of DX5+ NK cells was lower in the infection group than in the control group (t = -6.56, P < 0.05). RT-qPCR assay revealed that the relative PD-1, PD-L1, and DX5 mRNA expression was (1.010 ± 0.005), (1.002 ± 0.003), and (1.001 ± 0.001) in the JEG-3 cells and NK92MI cells co-culture system and (3.638 ± 1.258), (0.397 ± 0.158), and (4.267 ± 1.750) in the control group, and ELISA measured that the TNF-α concentration was higher in the cell culture supernatant in the infection group [(22.056 ± 3.205) pg/mL] than in the control group [(12.441 ± 0.001) pg/mL] (t = 5.20, P < 0.05). The PD-1(t = 3.62, P < 0.05) and DX5 mRNA expression (t = 3.23, P < 0.05) was higher in the infection group than in the control group, and the PD-L1 mRNA expression was lower in the infection group than in the control group (t = -6.63, P < 0.05). Conclusions Following T. gondii infection, both PD-L1 expression and PD-1 expression on DX5+ NK cells at the maternal-fetal interface are upregulated in mice during the second trimester; however, the proportion of DX5+ NK cells decreases. These findings suggest that PD-1/PD-L1 signaling may suppress NK cell functions by modulating DX5+ NK cell subsets.
4.Artificial intelligence in drug development for delirium and Alzheimer's disease.
Ruixue AI ; Xianglu XIAO ; Shenglong DENG ; Nan YANG ; Xiaodan XING ; Leiv Otto WATNE ; Geir SELBÆK ; Yehani WEDATILAKE ; Chenglong XIE ; David C RUBINSZTEIN ; Jennifer E PALMER ; Bjørn Erik NEERLAND ; Hongming CHEN ; Zhangming NIU ; Guang YANG ; Evandro Fei FANG
Acta Pharmaceutica Sinica B 2025;15(9):4386-4410
Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.
5.Investigation and analysis of pharmaceutical management in compact medical consortium of Guangdong province
Xiaodan ZHU ; Xiao CHEN ; Weiling CAO ; Yuan ZENG ; Zuojing LU ; Xuejun LI ; Wenying CHEN
China Pharmacy 2024;35(4):390-394
OBJECTIVE To investigate the current situation of pharmaceutical management in compact medical consortium of Guangdong province, and to provide decision-making basis for promoting the high-quality construction and sustainable development of the provincial medical consortium. METHODS A self-designed questionnaire was used to select 50 compact medical consortiums in Guangdong province. The survey was answered by the heads of the pharmacy department of the general hospitals. The survey covered the basic scale of the consortium, the appointment of chief pharmacists, the implementation of pharmaceutical management and pharmaceutical care homogenization within the consortium, the difficulties in promoting the homogenization, and the expected provincial support. Descriptive statistical analysis was performed on the survey results. RESULTS A total of 50 questionnaires were collected, and the effective recovery rate was 100%. There were 16 chief pharmacists (32.00%) in charge of the pharmacy department of the general hospital in the medical consortium. Thirty-seven medical consortiums (74.00%) had established a drug supply support system within the consortium, 35 medical consortiums (70.00%) had carried out pharmaceutical management and coordination work within the medical consortium, 23 medical consortiums (46.00%) had established a clinical medication guidance system, 25 medical consortiums chenwenying2016@163.com (50.00%) had established a bidirectional communication mechanism, and only 8 medical consortiums (16.00%) had developed new models of pharmaceutical care. At present, the difficulties in promoting the homogenization of pharmaceutical management and pharmaceutical care within the medical consortium were mainly found in three aspects: the wide gap in management level of each member unit, the lack and uneven level of pharmaceutical personnel, and insufficient policy support and implementation. Most medical consortiums hoped that relevant departments could promote the homogenization of pharmaceutical work by holding special training courses or special supervision. CONCLUSIONS At present, the compact medical consortium in Guangdong province has achieved initial results in the implementation of the chief pharmacist system, the homogenization of pharmaceutical management and pharmaceutical care. However, it is still necessary to improve the coverage of chief pharmacist appointments in the medical consortium, implement the homogenization of pharmaceutical management, and accelerate the homogenization process of pharmaceutical care.
6.Relationship between key molecules of IL-6/STAT3 signaling pathway and breast cancer susceptibility
Weijun CHEN ; Xiaodan WANG ; Jing DU ; Li LI ; Liguo GONG
Chinese Journal of Endocrine Surgery 2024;18(3):409-413
Objective:To investigate the relationship between key molecules of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway and breast cancer susceptibility.Methods:A case-control study design was adopted. 136 patients with breast cancer admitted to Department of Breast Surgery, Yantai Yantaishan Hospital from Mar. 2021 to Mar. 2023 were selected as the case group, and 136 healthy subjects of the same age were matched as the control group in a 1:1 ratio. The clinical data and key molecules of IL-6/STAT3 signaling pathway were compared between the two groups. The risk factors of breast cancer susceptibility were evaluated by conditional Logistic regression and addition analysis, and the diagnostic efficiency of receiver operating characteristic curve (ROC) and area under curve (AUC) were plotted.Results:The body mass index (BMI) (22.21±0.68 vs. 21.30±0.70 kg/m 2), age at menarche (13.50±1.24 years vs. 14.83±1.42 years), IL-6 (3.50±1.05 vs. 2.41±0.74), Janus protein kinase 1 (JAK1) mRNA (1.23±0.36 vs. 0.88±0.26), STAT3 mRNA (1.68±0.50 vs. 1.17±0.35), and menopause (30.15% vs. 55.88%), breastfeeding (82.35% vs. 92.65%), physical exercise (44.12% vs. 58.09%) were significantly different between the case group and the control group ( t=10.87, 8.23, 9.89, 9.19, 9.75, χ2=18.37, 6.59, 5.31, P<0.05). Breastfeeding [odd ratio ( OR) : 0.550], interleukin-6 (IL-6) ( OR: 4.409), janus protein kinase 1 (JAK1) ( OR: 5.370) and signal transducer and activator of transcription 3 (STAT3) ( OR: 4.386) mRNAs were risk factors for breast cancer susceptibility ( P<0.05). ROC curve showed that the combined diagnostic efficacy of IL-6, JAK1, STAT3 mRNA in breast cancer was significantly better than that of a single diagnostic efficacy. The incidence rate of breast cancer in those who were exposed to IL-6 mRNA and breast feeding was 3.508 times higher than that in those who were not exposed. The incidence rate of breast cancer in those who were exposed to JAK1 mRNA and breast feeding at the same time was 4.136 times higher than that in those who were not exposed. The incidence rate of breast cancer in those who were exposed to STAT3 mRNA and breast feeding was 3.537 times higher than that in those who were not exposed. Conclusion:The key molecules of IL-6/STAT3 signaling pathway and breast-feeding are predisposing factors of breast cancer, and they have additive interaction, thus increasing the susceptibility of breast cancer, which has significant practical significance for the differential diagnosis and treatment of this disease.
7.Comparative study on methods for colon polyp endoscopic image segmentation and classification based on deep learning
Jian CHEN ; Zhenni WANG ; Kaijian XIA ; Ganhong WANG ; Luojie LIU ; Xiaodan XU
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(6):762-772
Objective·To compare the performance of various deep learning methods in the segmentation and classification of colorectal polyp endoscopic images,and identify the most effective approach.Methods·Four colorectal polyp datasets were collected from three hospitals,encompassing 1 534 static images and 15 videos.All samples were pathologically validated and categorized into two types:serrated lesions and adenomatous polyps.Polygonal annotations were performed by using the LabelMe tool,and the annotated results were converted into integer mask formats.These data were utilized to train various architectures of deep neural networks,including convolutional neural network(CNN),Transformers,and their fusion,aiming to develop an effective semantic segmentation model.Multiple performance indicators for automatic diagnosis of colon polyps by different architecture models were compared,including mIoU,aAcc,mAcc,mDice,mFscore,mPrecision and mRecall.Results·Four different architectures of semantic segmentation models were developed,including two deep CNN architectures(Fast-SCNN and DeepLabV3plus),one Transformer architecture(Segformer),and one hybrid architecture(KNet).In a comprehensive performance evaluation of 291 test images,KNet achieved the highest mIoU of 84.59%,significantly surpassing Fast-SCNN(75.32%),DeepLabV3plus(78.63%),and Segformer(80.17%).Across the categories of"background","serrated lesions"and"adenomatous polyps",KNet's intersection over union(IoU)were 98.91%,74.12%,and 80.73%,respectively,all exceeding other models.Additionally,KNet performed excellently in key performance metrics,with aAcc,mAcc,mDice,mFscore,and mRecall reaching 98.59%,91.24%,91.31%,91.31%,and 91.24%,respectively,all superior to other models.Although its mPrecision of 91.46%was not the most outstanding,KNet's overall performance remained leading.In inference testing on 80 external test images,KNet maintained an mIoU of 81.53%,demonstrating strong generalization capabilities.Conclusion·The semantic segmentation model of colorectal polyp endoscopic images constructed by deep neural network based on KNet hybrid architecture,exhibits superior predictive performance,demonstrating its potential as an efficient tool for detecting colorectal polyps.
8.Oxymatrine hydrogel promotes wound healing by activating Nrf2/HO-1 pathway in keratinocytes
Lu LIU ; Shudan LIU ; Xiaodan LIU ; Li YANG ; Chen LING ; Xiaoming HAI ; Huiming MA ; Dongmei CHEN
Chinese Journal of Tissue Engineering Research 2024;28(29):4620-4627
BACKGROUND:Inflammation and oxidative stress contribute to the barriers of regeneration in chronic wound.Oxymatrine has various biological activities,such as anti-oxidation,anti-inflammation and so on,which may have the potential effect of promoting wound healing. OBJECTIVE:To investigate the effect of oxymatrine on wound healing and the protective effect on H2O2-induced oxidative stress injury in human keratinoid cell line HaCaT cells. METHODS:(1)In vivo experiment:Hyaluronic acid methacryloyl hydrogels containing 0,0.05,0.1,0.2 g/L oxymatrine were prepared.A full-layer skin defect model with a diameter of 12 mm was made in the back of 75 diabetic mice and randomly divided into five groups for intervention,with 15 mice in each group.The wounds of the model group were bandaged and fixed.The wounds of the hydrogel group were covered with hyaluronic acid methacryloyl hydrogel.The wounds of the low-dose,moderate-dose and high-dose oxymatrine groups were covered with hyaluronic acid methacryloyl hydrogel containing 0.05,0.1,and 0.2 g/L oxymatrine,respectively,and then bandaged and fixed after light curing.Relevant indicators were detected within 14 days.(2)In vitro experiment:Human keratinocyte line HaCaT was divided into five groups.The normal group was cultured conventionally.H2O2 group and low-,moderate-and high-concentration oxymatrine groups were treated with H2O2 for 4 hours,and then the medium was replaced with medium containing 0,0.05,0.1,and 0.2 g/L oxymatrine,respectively,and the relevant indexes were detected after 24 hours of culture. RESULTS AND CONCLUSION:(1)In vivo experiment:Compared with the model group,the wound healing rate of mice in the hydrogel group had no significant change.The wound healing rate of mice in the low-,moderate-and high-dose oxymatrine group was increased at 7 and 14 days after treatment(P<0.05).Pathological observation of wound section 14 days after treatment showed that compared with the model group,the thickness of regenerated epidermal layer,the number of microvessels,and collagen deposition in the moderate-and high-dose oxymatrine groups were increased(P<0.05).Western blot assay analysis of wound samples 7 days after surgery showed that compared with the model group,the protein expressions of tumor necrosis factor α and interleukin 6 in the moderate-and high-dose oxymatrine groups were decreased(P<0.05).(2)In vitro experiment:CCK8 assay,EdU and Ki67 staining showed that compared with the H2O2 group,the cell proliferation ability of the moderate-and high-concentration oxymatrine groups was significantly increased(P<0.05).Compared with the H2O2 group,mitochondrial membrane potential was increased(P<0.05)and reactive oxygen species content was decreased(P<0.05)in the moderate-and high-concentration oxymatrine groups.Western blot assay results showed that compared with the H2O2 group,the expression levels of Nrf2 nuclear protein,Nrf2 total protein,HO-1 protein,and superoxide dismutase 1 protein were increased in the high-concentration oxymatrine group(P<0.05).(3)These findings confirm that oxymatrine can alleviate oxidative stress damage in HaCat cells and accelerate wound healing by upregulating the levels of Nrf2 and HO-1 protein.
9.Aerobic exercise upregulates the thioredoxin system and inhibits cardiomyocyte apoptosis in aging rats
Zheng XU ; Xiaoqin ZHAO ; Xiaodan CHEN ; Jiapu WANG ; Fenmiao BAO ; Liang YU ; Junping LI ; Yan WEI
Chinese Journal of Tissue Engineering Research 2024;28(34):5508-5515
BACKGROUND:Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process.Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis,hypertrophy,and fibrotic damage. OBJECTIVE:To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats. METHODS:Thirty-six male Sprague-Dawley rats were selected and divided into three age groups:3-month-old young group,9-month-old middle-aged group,and 18-month-old elderly group,with 12 rats in each group.Within each age group,rats were randomly assigned to sedentary and exercise subgroups(n=6 per group).The sedentary groups did not undergo any exercise intervention.The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day,at a speed of 15 m/min,5 days per week for 10 weeks in total.At 24 hours after the final intervention,ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats.TUNEL assay was utilized to detect cardiomyocyte apoptosis,while western blot assay was employed to assess the protein expression of Bax,Bcl-2,Caspase 3,thioredoxin-1,thioredoxin-2,thioredoxin reductase-1,thioredoxin reductase-2,thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardial tissue. RESULTS AND CONCLUSION:Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group(P<0.01).Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group(P<0.01).Positive apoptotic cells in rat myocardial tissue,along with increased protein expression of Bax and Caspase 3,exhibited an age-related upward trend,while Bcl-2 protein expression showed a declining trend.In comparison with the sedentary groups within each age category,the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees,and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups.Compared with the young sedentary group,middle-aged sedentary group and elderly exercise group,elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1,thioredoxin 2,thioredoxin reductase 1,and thioredoxin reductase 2 proteins(P<0.05,P<0.01).The expression of myocardial thioredoxin 1,thioredoxin 2,and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group(P<0.05,P<0.01),while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group,middle-aged sedentary group and elderly exercise group(P<0.01).The protein expression of thioredoxin-interacting protein,apoptosis signal-regulating kinase 1,and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group(P<0.01).To conclude,aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts,leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein,thereby alleviating myocardial cell apoptosis in aging rat hearts.
10.Eugenol attenuates the inflammation of Fusarium-induced keratitis through PI3K/AKT signaling pathway
Hui DING ; Shisi HU ; Zhenduo YANG ; Xiaodan CHEN
International Eye Science 2024;24(8):1194-1199
AIM: To investigate the protective effect of eugenol against Fusarium solani(F.solani)-induced fungal keratitis(FK)in mice and to preliminarily explore possible underlying mechanisms.METHODS: A modified epifluorescence microscopy method was used to prepare the FK mouse model. An equal amount of DMSO(0.05%)was applied to the conjunctiva of the right eye of rats in the dimethyl sulfoxide(DMSO)group. The eugenol group was prepared by applying eugenol(160 μg/mL)to the conjunctival sac of the right eye of mice. The insulin-like growth factor-1(IGF-1)group was coated with the PI3K/AKT pathway activator IGF-1(10 nmol/mL)in the conjunctival sac of the right eye in addition to the administration of eugenol. The corneal morphology was observed under a slit-lamp microscope on days 1, 3, and 5 of inoculation with F.solani suspension, respectively. Hematoxylin eosin(HE)staining was used to assess corneal histopathological damage. The bacterial load of corneal tissue was determined. Enzyme-linked immunosorbent assay and Western blot were used to analyze the levels of inflammatory mediators interleukin-6(IL-6)and interleukin-1β(IL-1β)and the expression of PI3K/AKT pathway proteins.RESULTS: Eugenol treatment improved the morphological symptoms of keratitis and inflammatory response in FK mice, and reduced corneal pathologic tissue damage and fungal load. At 3 d after F.solani infection, corneal tissue IL-6 levels were significantly higher and IL-1β levels were significantly lower in the eugenol group compared with the DMSO group(both P<0.05); corneal tissue IL-6 levels were significantly higher and IL-1β levels were significantly lower in the eugenol group than in the IGF-1 group(both P<0.05). At 5 d after infection, both IL-6 and IL-1β levels in corneal tissue of the eugenol group were significantly lower than those of the DMSO and IGF-1 groups(P<0.05); compared with the DMSO group, the expression of p-PI3K and p-Akt in the corneal tissues of the eugenol group was significantly reduced(P<0.05); the expression of p-PI3K and p-Akt in corneal tissues was significantly lower in the eugenol group than that of the IGF-1 group(both P<0.05).CONCLUSION: Eugenol may attenuate F.solani-induced corneal inflammation by inhibiting the PI3K/AKT pathway, and it has a protective effect against F.solani keratitis in mice.

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