1.Effects of lncRNA RP11-499E18.1 on the malignant biological behavior of ovarian cancer cells.
Journal of Central South University(Medical Sciences) 2025;50(1):1-10
OBJECTIVES:
Ovarian cancer is a common gynecologic malignancy, with poor prognosis in advanced stages. This study aimed to identify differentially expressed long noncoding RNA (lncRNA) associated with ovarian cancer prognosis and to explore the effects of lncRNA RP11-499E18.1 on the malignant biological behavior of ovarian cancer cells.
METHODS:
Ovarian cancer-related lncRNA datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed and prognostically relevant tumor-suppressive lncRNAs were screened using lncRNA sequencing combined with clinical data. Reverse transcription PCR (RT-PCR) was used to detect the expression of lncRNA RP11-499E18.1 in ovarian cancer tissues, adjacent normal tissues, the IOSE80 normal ovarian epithelial cell line, and various ovarian cancer cell lines. Fluorescence in situ hybridization (FISH) was performed to determine its subcellular localization. Ovarian cancer cell lines CaOV3 and SKOV3 were divided into 3 groups: a negative control (NC) group, a knockdown (si-RP11-499E18.1) group, and a overexpression (pcDNA-RP11-499E18.1) group. Methyl thiazolyl tetrazolium (MTT) and Transwell assays were used to assess the effects of lncRNA RP11-499E18.1 on cell proliferation and migration. Western blotting was used to evaluate its effect on epithelial-mesenchymal transition (EMT)-related molecules. BALB/c nude mice were injected with CaOV3 cells transfected with pcDNA-RP11-499E18.1 (experimental group) or empty vector (control group), and tumor growth was monitored. Immunohistochemistry was used to assess the expression of Caspase 3 and Ki67 in tumor tissues.
RESULTS:
LncRNA sequencing identified RP11-499E18.1 as a differentially expressed and associated with prognosis. GEO data analysis showed that low RP11-499E18.1 expression was correlated with shorter overall and progression-free survival (both P<0.05). Its expression was significantly lower in ovarian cancer tissues and cell lines compared to normal controls (P<0.05 or P<0.001), and it was localized in both the nucleus and cytoplasm. In CaOV3 and SKOV3 cells, proliferation rates increased significantly in the si-RP11-499E18.1 group and decreased in the pcDNA-RP11-499E18.1 group (P<0.05 or P<0.001). Cell migration was enhanced in the si-RP11-499E18.1 group and suppressed in the pcDNA-RP11-499E18.1 group. Overexpression increased E-cadherin and decreased vimentin expression, while knockdown had the opposite effect. Tumor volume in the mouse model was significantly smaller in the experimental group (P<0.001), with increased Caspase 3 and decreased Ki67 expression in tumor tissues (both P<0.05).
CONCLUSIONS
LncRNA RP11-499E18.1 inhibits proliferation, migration, and EMT of ovarian cancer cells, and its low expression is associated with poor prognosis.
Female
;
Humans
;
RNA, Long Noncoding/physiology*
;
Ovarian Neoplasms/pathology*
;
Cell Line, Tumor
;
Animals
;
Mice
;
Mice, Nude
;
Cell Proliferation
;
Prognosis
;
Mice, Inbred BALB C
;
Gene Expression Regulation, Neoplastic
;
Cell Movement
;
Epithelial-Mesenchymal Transition
2.Incomplete multimodal bone tumor image classification based on feature decoupling and fusion.
Qinghai ZENG ; Chuanpu LI ; Wei YANG ; Liwen SONG ; Yinghua ZHAO ; Yi YANG
Journal of Southern Medical University 2025;45(6):1327-1335
OBJECTIVES:
To construct a bone tumor classification model based on feature decoupling and fusion for processing modality loss and fusing multimodal information to improve classification accuracy.
METHODS:
A decoupling completion module was designed to extract local and global bone tumor image features from available modalities. These features were then decomposed into shared and modality-specific features, which were used to complete the missing modality features, thereby reducing completion bias caused by modality differences. To address the challenge of modality differences that hinder multimodal information fusion, a cross-attention-based fusion module was introduced to enhance the model's ability to learn cross-modal information and fully integrate specific features, thereby improving the accuracy of bone tumor classification.
RESULTS:
The experiment was conducted using a bone tumor dataset collected from the Third Affiliated Hospital of Southern Medical University for training and testing. Among the 7 available modality combinations, the proposed method achieved an average AUC, accuracy, and specificity of 0.766, 0.621, and 0.793, respectively, which represent improvements of 2.6%, 3.5%, and 1.7% over existing methods for handling missing modalities. The best performance was observed when all the modalities were available, resulting in an AUC of 0.837, which still reached 0.826 even with MRI alone.
CONCLUSIONS
The proposed method can effectively handle missing modalities and successfully integrate multimodal information, and show robust performance in bone tumor classification under various complex missing modality scenarios.
Humans
;
Bone Neoplasms/diagnosis*
;
Multimodal Imaging/methods*
;
Magnetic Resonance Imaging
;
Tomography, X-Ray Computed
;
Image Processing, Computer-Assisted/methods*
;
Algorithms
3.Study on the Mechanism of Tongluo Baoshen Decoction in Regulating Gprc5b/NF-κB/NLRP3 Pathway to Improve Podocyte Injury in IgA Nephropathy Rats
Yongfang LIU ; Li ZHOU ; Huiyang LIU ; Jianfeng DAI ; Yinghua LIU ; Bangming CHEN ; Xuefei LIN ; Taiwang YANG ; Xingyu LIU ; Yi FU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):112-120
Objective To explore the mechanism of Tongluo Baoshen Decoction in improving podocyte injury in rats with IgA nephropathy based on Gprc5b/NF-κB/NLRP3 pathway.Methods Totally 130 SPF-grade male SD rats were randomly divided into a normal group(n=20)and a modeling group(n=110).The IgA nephropathy model was established using a compound modeling method,and 100 modeling rats were randomly divided into model group,losartan potassium group(5 mg/kg),and Tongluo Baoshen Decoction low-,medium-,and high-dosage groups(5.3,10.6,21.2 g/kg),with 20 rats in each group.The administration group was given the corresponding dosage of medication by gavage,while the normal group and model group were given an equal amount of distilled water by gavage once a day.After 4 and 8 weeks of administration,urine samples were collected for 24 hours,and blood and kidney tissue specimens were collected.24-hour urinary protein quantification(24 h-UTP),urinary Nephrin,serum creatinine(SCr),blood urea nitrogen(BUN)and blood uric acid(BUA)contents were detected;RT-qPCR and Western blot were used to detect the expressions of G protein coupled receptor C-family 5b(Gprc5b),nuclear factor(NF)-κB p50,NOD like receptor protein 3(NLRP3),Caspase-1,interleukin(IL)-1β,Nephrin mRNA and protein in renal tissue,respectively;HE,PAS,PASM,Masson staining were used to observe the morphology of renal tissue,immunofluorescence was used to observe IgA deposition in the mesangial area of renal tissue,and transmission electron microscopy was used to observe the ultrastructure of podocytes.Results Compared with the normal group,the model group rats showed significantly increased contents of 24 h-UTP,urinary Nephrin and BUA(P<0.01),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue were significantly increased(P<0.01),while the mRNA and protein expressions of Nephrin were significantly decreased(P<0.01),with mild to moderate proliferation of mesangial cells in the glomerulus,increased mesangial matrix,and immunofluorescence showed clustered and linear deposition of IgA in the mesangial area,electron microscopy showed partial fusion of the foot processes.Compared with the model group,the 24 h-UTP and urinary Nephrin contents in different dosage groups of Tongluo Baoshen Decoction and the losartan potassium group after 4 and 8 weeks administration significantly decreased(P<0.01),with a decrease in BUA content in Tongluo Baoshen Decoction high-dosage group(P<0.05),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue of Tongluo Baoshen Decoction groups and losartan potassium group decreased(P<0.05,P<0.01),while the mRNA and protein expressions of Nephrin increased(P<0.05,P<0.01),with the proliferation of mesangial cells,the increase of mesangial matrix,the deposition of IgA in the mesangial area,and the fusion of foot processes in renal tissue were alleviated to varying degrees in different dosage groups of Tongluo Baoshen Decoction,with the most significant improvement observed in the high-dosage group.Compared with the 4-week administration,Tongluo Baoshen Decoction high-dose group showed further reductions in 24 h-UTP and urinary Nephrin contents after 8 weeks of administration(P<0.01),further decreases in the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue(P<0.05,P<0.01),and further increases in the mRNA and protein expressions of Nephrin(P<0.01).Conclusion Tongluo Baoshen Decoction can reduce proteinuria,alleviate renal tissue lesions and improve podocyte injury in IgA nephropathy rats,and its mechanism may be related to the inhibition of Gprc5b/NF-κB/NLRP3 pathway in renal tissue.
4.Correlation between bedtime screen use behavior and sleep health among fourth and fifth grade primary school students
ZHU Guiyin, ZHU Fan, QI Tiantian, GUO Shihao, YANG Shuang, MA Yinghua
Chinese Journal of School Health 2025;46(4):548-551
Objective:
To investigate the association between bedtime screen use and sleep health among fourth and fifthgrade primary school students, so as to provide evidence to support interventions for improving sleep quality.
Methods:
From April to June 2024, a survey was conducted among 4 232 fourth and fifthgrade students from nine primary schools in a district of Beijing. A selfdesigned questionnaire assessed bedtime screen use behavior and sleep health indicators. Generalized linear models and Logistic regression were used to analyze the associations.
Results:
Among the surveyed students, 28.3% reported bedtime screen use. Mean sleep duration every day was (9.31±0.90) hours on school days and (10.08±1.36) hours on weekends. Compared to nonusers, students with bedtime screen use exhibited every day: later bedtimes on school days (10.18 min delay, 95%CI=6.88-13.47) and weekends (22.09 min delay, 95%CI=17.33-26.85) (P<0.05); later weekend wake times (7.97 min delay, 95%CI=1.78-14.16, P<0.05); reduced sleep duration on school days (-9.82 min, 95%CI=-13.62 to -6.03) and weekends (-14.12 min, 95%CI=-20.24 to -8.00) (P<0.05); greater weekend-school day bedtime discrepancy (β=1.15, 95%CI=1.08-1.23, P<0.01). Additionally, they had lower odds of falling asleep within 20 minutes (OR=0.62, 95%CI=0.54-0.72), daytime alertness (OR=0.66, 95%CI=0.56-0.77), and subjective sleep satisfaction (OR=0.57, 95%CI=0.49-0.66)(P<0.01).
Conclusions
Bedtime screen use is associated with adverse effects on multiple dimensions of sleep health in primary school students. Reducing screen exposure before bed may help improve their sleep quality.
5.Preliminary development of Health Literacy Evaluation Scale for Chinese High School Students
GUO Shihao, ZHU Fan, ZHU Guiyin, QI Tiantian, YANG Shuang, HU Bin, WU Huiyun, JIANG He, MA Yinghua
Chinese Journal of School Health 2025;46(5):676-680
Objective:
To develop a health literacy evaluation scale for Chinese high school students, providing a tool for dynamic monitoring of health literacy among high school students and evaluating the effectiveness of health school construction.
Methods:
Through theoretical research, an evaluation index system for health literacy of Chinese high school students was constructed. Two rounds of Delphi expert consultations were conducted to quantitatively screen the items, and the item pool was revised based on expert opinions to compile the health literacy evaluation scale for Chinese students. Two focus group interviews were held to collect suggestions from health educators, high school teachers, and high school students regarding optimized scale length, question types, difficulty and wording of the scale. The scale was revised accordingly. A pilot survey was conducted in Beijing and Tianjin in November 2024, and the reliability and validity of the scale were evaluated based on the pilot survey data.
Results:
The response rate in both rounds of Delphi expert consultations was over 80%, and the expert authority coefficient was over 0.70. The expert opinions were highly concentrated, and the dispersion was small. The revised item pool based on expert opinions contained 39 items. The revised scale based on the suggestions and opinions collected from the focus group interviews had a moderate number of questions and difficulty level. The pilot survey obtained 800 valid responses, with the response rate of 89.39%. The Cronbach α coefficient of the scale was 0.911, χ 2/df =3.321, the root mean square error of approximation was 0.054, the adjusted goodness-of-fit index was 0.991 , and the factor loadings of some items were less than 0.40.
Conclusion
The health literacy evaluation scale for Chinese high school students demonstrates scientific rigor and practical applicability, with good internal consistency and structural validity.
6.Preliminary development with reliability and validity testing of health literacy assessment scale for junior high school students
QI Tiantian, ZHU Fan, ZHU Guiyin, GUO Shihao, YANG Shuang, WU Huiyun, HU Bin, JIANG He, MA Yinghua
Chinese Journal of School Health 2025;46(6):816-820
Objective:
To develop and validate a health literacy assessment scale for junior high school students, providing an effective tool for evaluating and monitoring health literacy among Chinese adolescents.
Methods:
Based on school health education policy documents, a health literacy assessment framework was constructed, comprising five horizontal and four vertical dimensions. From May to June and August to September in 2024, the framework was refined through Delphi expert consultations and focus group discussions, leading to the development of the Health Literacy Assessment Scale for Junior High School Students. In September 2024, a convenience sample of 625 students from three junior high schools in Beijing and Tianjin completed the questionnaire. Item analysis, reliability, and validity tests were conducted to evaluate the scale.
Results:
The recovery rate for two rounds of expert consultation questionnaires was 100%. The expert authority coefficients ( Cr ) were 0.86 and 0.87 respectively (both >0.70), with Kendall W values of 0.34 and 0.27 ( P <0.05). The focus group discussions followed a rigorous structure, and after multiple rounds of item screening and revision, the version 3.0 of the junior high school students health literacy assessment scale was developed, comprising 57 items. Three items that failed to meet the comprehensive screening criteria were preliminarily removed, and the final scale contained 54 items. The scale demonstrated excellent reliability, with an overall Cronbach s α coefficient of 0.92 and split half reliability of 0.93. Confirmatory factor analysis [ χ 2/df =2.094, root mean square error of approximation ( RMSEA )=0.042, comparative fit index ( CFI )=0.911, Tucker Lewis index ( TLI )=0.907] indicated good model fit indices.
Conclusions
The preliminary development of the health literacy assessment scale for junior high school students follows a rigorous item screening process with well designed dimensions, demonstrating good reliability and validity, thus serving as an appropriate evaluation tool for adolescent health literacy.
7.Regulatory role of ITCH-TXNIP-NLRP3 signaling pathway in Alzheimer disease-like lesions in vivo and in vitro
Qiuyu XIE ; Jianfeng MA ; Qiying SHEN ; Yongxiang HE ; Xiaobing LI ; Shuo YANG ; Yuke XIANG ; Yuan QIN ; Wei WEI ; Yinghua LIU
Chinese Journal of Pathophysiology 2025;41(6):1109-1117
AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.
8.Effects of 12.5% carbohydrate solution and MCT solutions at various concentrations on gastric emptying in healthy volunteers
Jinran YANG ; Ruilan NIU ; Lin ZHENG ; Xiangrong LIU ; Xinsheng ZHANG ; Yinghua LIU
Chinese Journal of Clinical Nutrition 2025;33(1):40-47
Objective:To observe the effects of 12.5% carbohydrate (CHO) solution and medium chain triglycerides (MCT) solutions at various concentrations on gastric emptying, in order to determine the optimal MCT-CHO combination for enhanced recovery after surgery.Methods:This study was a prospective study. Ten healthy volunteers were selected to ingest 400 ml of the following 5 solutions every day: water, 12.5% CHO, 1% MCT, 2% MCT and 4% MCT. According to the above results, the optimal concentration of MCT solution was 2% MCT, showing comparable gastric emptying rate compared with 12.5% CHO solution. On this basis, combinations of MCT and CHO solutions were determined to be 30 energy % (EN%) MCT+70 EN% CHO and 20 EN% MCT+80 EN% CHO according to the energy distribution ratio. Then the volunteers were given 400 ml of the following 4 solutions every day: 12.5% CHO, 2% MCT, 30 EN% MCT+70 EN% CHO (equivalent to 2% MCT+8% CHO), and 20 EN% MCT+80 EN% CHO (equivalent to 4.4% MCT+10% CHO). Gastric emptying during fasting (T m) and immediately (T 1), 30 min (T 2), 60 min (T 3), 90 min (T 4) and 120 min after ingestion (T 5) were observed by antral ultrasonography. The degree of thirst, hunger, and anxiety was assessed by Visual Analogue Scale, and the taste was rated. Results:The gastric emptying rate in descending order was 20%EN MCT+80%EN CHO group>30%EN MCT+70%EN CHO group≈2%MCT group≈12.5%CHO group. There was no significant difference in gastric emptying rate between 30 EN% MCT+70 EN% CHO group and 12.5% CHO group ( P>0.05). The scores of thirst, hunger and anxiety in 30 EN% MCT+70 EN% CHO group at T 1 to T 5 were significantly lower than those at T m ( P<0.05). 30 EN% MCT+70 EN% CHO group showed the highest taste score. Conclusion:30 EN% MCT+70 EN% CHO solution has similar gastric emptying rate compared with 12.5% CHO solution. It can relieve thirst, hunger, anxiety and other subjective feelings caused by fasting, with tastes better than 12.5% CHO solution.
9.Effects of 12.5% carbohydrate solution and MCT solutions at various concentrations on gastric emptying in healthy volunteers
Jinran YANG ; Ruilan NIU ; Lin ZHENG ; Xiangrong LIU ; Xinsheng ZHANG ; Yinghua LIU
Chinese Journal of Clinical Nutrition 2025;33(1):40-47
Objective:To observe the effects of 12.5% carbohydrate (CHO) solution and medium chain triglycerides (MCT) solutions at various concentrations on gastric emptying, in order to determine the optimal MCT-CHO combination for enhanced recovery after surgery.Methods:This study was a prospective study. Ten healthy volunteers were selected to ingest 400 ml of the following 5 solutions every day: water, 12.5% CHO, 1% MCT, 2% MCT and 4% MCT. According to the above results, the optimal concentration of MCT solution was 2% MCT, showing comparable gastric emptying rate compared with 12.5% CHO solution. On this basis, combinations of MCT and CHO solutions were determined to be 30 energy % (EN%) MCT+70 EN% CHO and 20 EN% MCT+80 EN% CHO according to the energy distribution ratio. Then the volunteers were given 400 ml of the following 4 solutions every day: 12.5% CHO, 2% MCT, 30 EN% MCT+70 EN% CHO (equivalent to 2% MCT+8% CHO), and 20 EN% MCT+80 EN% CHO (equivalent to 4.4% MCT+10% CHO). Gastric emptying during fasting (T m) and immediately (T 1), 30 min (T 2), 60 min (T 3), 90 min (T 4) and 120 min after ingestion (T 5) were observed by antral ultrasonography. The degree of thirst, hunger, and anxiety was assessed by Visual Analogue Scale, and the taste was rated. Results:The gastric emptying rate in descending order was 20%EN MCT+80%EN CHO group>30%EN MCT+70%EN CHO group≈2%MCT group≈12.5%CHO group. There was no significant difference in gastric emptying rate between 30 EN% MCT+70 EN% CHO group and 12.5% CHO group ( P>0.05). The scores of thirst, hunger and anxiety in 30 EN% MCT+70 EN% CHO group at T 1 to T 5 were significantly lower than those at T m ( P<0.05). 30 EN% MCT+70 EN% CHO group showed the highest taste score. Conclusion:30 EN% MCT+70 EN% CHO solution has similar gastric emptying rate compared with 12.5% CHO solution. It can relieve thirst, hunger, anxiety and other subjective feelings caused by fasting, with tastes better than 12.5% CHO solution.
10.Regulatory role of ITCH-TXNIP-NLRP3 signaling pathway in Alzheimer disease-like lesions in vivo and in vitro
Qiuyu XIE ; Jianfeng MA ; Qiying SHEN ; Yongxiang HE ; Xiaobing LI ; Shuo YANG ; Yuke XIANG ; Yuan QIN ; Wei WEI ; Yinghua LIU
Chinese Journal of Pathophysiology 2025;41(6):1109-1117
AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.


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