1.Treadmill Exercise Attenuates Hippocampal Neuroinflammation and Ameliorates Cognitive Dysfunction in Methamphetamine-Addicted Mice: Transcriptomic Screening Identifies NLRC5 as a Candidate Molecule
Guo-Si YING ; Qiu-Yue HUANG ; Ji-Sheng XU ; Xue-Jie ZHANG ; Ya-Rui DANG ; Xue LI
Progress in Biochemistry and Biophysics 2026;53(10):2820-2834
ObjectiveTreadmill exercise intervention was evaluated for its effects on addictive behavior, learning and memory, and hippocampal neuroinflammation in methamphetamine (MA)-addicted mice, and transcriptomic screening was performed to identify candidate molecules involved in exercise-mediated attenuation of MA-related neuronal injury. MethodsTwo-month-old male C57BL/6 mice were randomly assigned to four groups: control (C), exercise control (CE), methamphetamine (M), and methamphetamine plus exercise (ME). Mice in the M and ME groups received intraperitoneal injections of MA (1 mg/kg) once daily for 7 consecutive days to establish the addiction model, whereas mice in the C and CE groups received equal volumes of saline. Subsequently, mice in the CE and ME groups underwent treadmill exercise at 12 m/min for 60 min/d for 2 weeks. Conditioned place preference (CPP), the Y-maze, and the Morris water maze (MWM) were used to assess addictive behavior, spatial recognition memory, and spatial learning and memory, respectively. Hippocampal neuronal ultrastructure was examined by transmission electron microscopy (TEM), and microglia-related responses were evaluated by immunofluorescence staining for ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampal CA1 region. Previously generated and publicly available RNA-seq data from brain tissue of the C, M, and ME groups were reanalyzed, with three biological samples per group. Differentially expressed genes (DEGs) were re-screened using the criteria of P<0.05 and fold change>1.5 or <0.67, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. NLR family CARD domain containing 5 (Nlrc5) was further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot was used to determine the protein expression of NLRC5, nuclear factor kappa B (NF‑κB), interleukin-1β (IL-1β), postsynaptic density-95 (PSD-95), and synaptophysin. ResultsTreadmill exercise significantly attenuated MA-induced conditioned place preference and improved learning and memory performance in both the Y-maze and MWM tests. Exercise increased exploration time and distance in the novel arm of the Y-maze, shortened escape latency, and increased the number of platform crossings in the MWM. Average swimming speed during the probe trial did not differ significantly among groups, suggesting that the MWM differences were not attributable to obvious differences in swimming performance. TEM revealed that MA exposure induced mitochondrial swelling, disrupted cristae, reduced organelle abundance, and nuclear envelope abnormalities in hippocampal neurons, whereas these ultrastructural changes were alleviated after exercise. Immunofluorescence staining showed that MA increased Iba-1 fluorescence intensity in the hippocampal CA1 region, while treadmill exercise significantly reduced this change. Transcriptomic analysis identified 160 DEGs associated with MA exposure and 58 DEGs associated with exercise intervention, with 9 overlapping DEGs. KEGG enrichment analysis showed that MA-related DEGs were enriched in the NOD-like receptor signaling pathway. Among the overlapping DEGs, Nlrc5, which was downregulated after MA exposure and restored following exercise intervention, was selected as a candidate gene for further validation. RT-qPCR confirmed that treadmill exercise reversed the MA-induced decrease in Nlrc5 mRNA expression. Western blot analysis further showed that treadmill exercise increased NLRC5, PSD-95, and synaptophysin protein expression while reducing NF-κB and IL-1β expression. ConclusionTwo weeks of treadmill exercise attenuated MA-induced conditioned place preference and ameliorated learning and memory impairment, alleviated hippocampal neuroinflammation and neuronal ultrastructural damage, and restored the expression of synapse-related proteins. Transcriptomic screening combined with molecular validation demonstrated that exercise intervention was accompanied by restoration of NLRC5 expression, reduced NF‑κB and IL-1β expression, and increased PSD-95 and synaptophysin expression. These findings suggest that NLRC5 may represent a candidate molecule involved in exercise-mediated amelioration of MA-related neuronal injury. However, the present results mainly demonstrate coordinated changes in NLRC5 expression, inflammatory indicators, and cognitive outcomes rather than a direct causal relationship, and the specific role of NLRC5 requires further functional validation.
2. Effect of ~(56)Fe~(17+) heavy ion on the expression of phosphorylated histone H2AX of human lymphocytes
Juan-Cong DONG ; Ya-Yi YUAN ; Rui-Feng ZHANG ; Xu-Hong DANG ; Zhong-Xin ZHANG ; Jian-Gong LIU ; Ya-Hui ZUO ; Zhi-Kai DUAN
China Occupational Medicine 2016;43(04):471-474
OBJECTIVE: To explore the effect of~(56)Fe~(17+)heavy ion on the expression of phosphorylated histone H2AX( γH2AX) of human lymphccytes. METHODS: The Epstein-Barr virus transformed human B lymphocyte cell lines( PengEBV) were selected and exposed to~(56)Fe~(17+)heavy ion at irradiation dose of 0. 0( control group),0. 1,0. 3,0. 5,0. 7,1. 0 and 2. 0 Gy,respectively,with the dosing rate of 0. 23-0. 55 Gy / min. Flow-cytometry was used to detect the changes of expression of γH2AX at time points of 0,2,4,8,48 and 72 hours after irradiation. RESULTS: The expression of γH2AX showed interaction existed between radiation dose and the treatment time after radiation( P < 0. 01). Compared with the control at the same time points,the expression of γH2AX increased at the dose of 0. 3-2. 0 Gy and the time points of 2-72hours( P < 0. 05). The expression of γH2AX at the dose of 0. 3-2. 0 Gy and time points of 8-72 hours was lower than those at the same dose and time points of 2 and 4 hours( P < 0. 05). When the dose was at 0. 5,1. 0 or 2. 0 Gy,the expression of γH2AX decreased with the increasing time of exposure in 72 hours( P < 0. 05). At the dose of 0. 0-1. 0 Gy and the time points of 2-4 hours,the expression of γH2AX increased with the increasing dose of irradiation( P < 0. 01). CONCLUSION: The expression of γH2AX in Peng-EBV cells shows a dose-response relationship within 2-4 hours after 0. 0-1. 0 Gy irradiation of~(56)Fe~(17+).
3.Relationship between female menopause and hypertension/isolated systolic hypertension in rural districts of Hanzhong in Shaanxi province.
Shi-hua FANG ; Hong YAN ; Shao-nong DANG ; Qiang LI ; Ya-ling ZHAO ; Rui-hai YANG ; Yong REN
Acta Academiae Medicinae Sinicae 2013;35(4):422-426
OBJECTIVETo analyze the associations between menopause and hypertension/isolated systolic hypertension (ISH) among rural females in Hanzhong, Shaanxi Province, China.
METHODSIn this cross-sectional study, 3030 residents were selected by stratified random sampling and investigated by questionnaire survey and physical examinations. Data of the females were analyzed to explore the impact of menopause on blood pressure by quantile regression and to investigate the associations between menopause and hypertension, ISH, and isolated distolic hypertension (IDH) by logistic regression.
RESULTSThe number of premenopausal and postmenopausal women was 965 and 998. The average age was (41.0 ± 8.07) years in the premenopausal group and (58.0±7.12) years in the postmenopausal group (P<0.001). The prevalence of hypertension among the premenopausal group and postmenopausal group was 21.9% and 49.3%, respectively. Quantiles regression analysis showed that the impact of menopause on systolic blood pressure increased as the percentile increased. The diastolic blood pressure (DBP) of the premenopausal group was significantly lower than that in the postmenopausal at q ≥ 0.40(DBP = 84 mmHg,1 mmHg = 0.133 kPa) percentile points (P<0.05), while the difference was not significant at q≤ 0.30 (DBP=80 mmHg) percentile points(P>0.05). After the potential confounders including age, education level, marriage, occupational, hyperlipidemia, family history, exercise, sleep, watching TV, smoking, passive smoking, alcohol consumption, body mass index, wealth index, waist circumference were controlled, positive associations were observed between menopause and hypertension/ISH in logistic regression models.
CONCLUSIONSMenopause is positively related with hypertension/ISH. More effective interventions should be taken to prevent hypertension and ISH among rural women.
Adult ; Aged ; Blood Pressure ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Hypertension ; epidemiology ; physiopathology ; Menopause ; Middle Aged ; Rural Population ; Surveys and Questionnaires
4.Survey on the prevalences of overweight and obesity in 9 rural areas in Hanzhong, Shaanxi province.
Lin REN ; Lei-lei PEI ; Hong YAN ; Shao-nong DANG ; Qiang LI ; Ya-ling ZHAO ; Xiao-ning LIU ; Rui-hai YANG ; Yong REN
Acta Academiae Medicinae Sinicae 2013;35(1):47-51
OBJECTIVETo investigate the prevalences of overweight and obesity in the rural communities in Hanzhong, Shaanxi Province.
METHODSA total of 3030 residents in the rural areas of Hanzhong city were selected by stratified random sampling method to take questionnaire-based survey and physical examinations.
RESULTSThe data of 3017 valid subjects (1048 men and 1969 women) entered the final analysis. The average body mass index was (22.9±4.2) kg/m(2) [(23.0±5.5) kg/m(2) in men and (22.9±3.2) kg/m(2) in women]. The prevalence rates of overweight and obesity were 27.9% and 5.9% respectively, and the standardized rates were 23.4% and 5.4%, respectively. More specifically, prevalence rates of overweight and obesity were 28.3% and 6.1% in men (standardized rates were 24.7% and 7.5%, respectively) and 27.6% and 5.8% (standardized rate were 22.8% and 4.5% respectively) in women. The overweight/obesity was more often in young and mid-aged married men with higher education and socioeconomic status and in middle-aged and older women with less education from wealthier households.
CONCLUSIONThe prevalences of overweight and obesity are relatively high in the rural areas of Hanzhong, and therefore effective interventions are warranted.
China ; epidemiology ; Female ; Humans ; Male ; Obesity ; epidemiology ; Prevalence ; Rural Population ; statistics & numerical data
5.Dietary patterns and its relationship with hypertension among rural residents in Hanzhong,Shaanxi province
Ru-Ru LIU ; Shao-Nong DANG ; Hong YAN ; Qiang LI ; Ya-Ling ZHAO ; Xiao-Ning LIU ; Rui-Hai YANG ; Yong REN
Chinese Journal of Epidemiology 2012;33(1):37-41
Objective To investigate the relationship between dietary patterns and hypertension in Hanzhong city of Shaanxi province.Methods A cross-sectional survey on dietarypattern and hypertension together with a semi-quantitative food frequency questionnaire was conducted among rural residents aged from 18 to 80 in Hanzhong of Shaanxi province in 2010.Factor analysis by SPSS was used to identify food patterns based on the frequency of food.Logistic regression was used to analyze the relationship between dietary patterns and hypertension.Results 2929 rural residents were investigated with an average age as 50.0 years old and average schooling-years as 6.8.The prevalence rate of hypertension was 34.3%,with 35.4% in males and 33.7% in females.Among 29 kinds of food under investigation,only 11 kinds with the frequencies of consumption more than 1 time per week.Four main factors were derived as four dietary patterns by factor analysis and they were diversity dietary pattern,alcohol dietary pattern,beverage dietary pattern and simple dietary pattern.Among them,the balanced dietary pattern was significantly associated with hypertension.All the participants were categorized into 4 groups (Q1-Q4) according to their factor scores,quartile with Q1 as a reference.The residents who were more closer to having balance dietary pattern,were under less risk of suffering from hypertension after controlling for age,sex,BMI,education and income.Compared to Q1,the Q4 had lower risk of hypertension (OR=0.59,95%CI:0.44-0.77) for the balanced pattern.Conclusion Dietary pattern could be related to the prevalence of hypertension.A rational diet with diversity of foods should be suggested as one of the major measures for the prevention of hypertension.
6.Relationships between smoking behavior and obesity in men from 9 rural districts of Hanzhong in Shaanxi province
Lin REN ; Lei-Lei PEI ; Hong YAN ; Shao-Nong DANG ; Qiang LI ; Ya-Ling ZHAO ; Xiao-Ning LIU ; Rui-Hai YANG ; Yong REN
Chinese Journal of Epidemiology 2012;33(9):907-911
Objectivc To examine the relationship between cigarette smoking and body mass index(BMI) as well as waist circumfcrcnce (WC) of men from 9 rural districts ofHanzhong,Shaanxi province.Methods Cross-sectional data was analyzed from Hanzhong Health Survey on rural residents in 2010.Quantile regression mode was used to compare the results using the BMI (WC) and smoking slatus (degree) as the dependent variables and independent variable and confounding factors were also controlled.Results 1039 rmale residents of rural areas of Hanzhong city were investigated.The prevalence rates on overweight and obesity among the males were 28.0% and 5.9%,with central obesity as 35.0% and the rate of currcnt cigarette smoking was 63.6% in the areas.Results from the quantile regression showed that the relationship between smoking status and BMI beyond 80 percentile in men (BMI=24.4) which was not significantly different BMI among the heavy smokers,was much higher than those mild smokers beyond 90 percentile (BMI=24.9).WC of the current smokers was significantly higher than those ex-smokers beyond the 95 percentile (WC=96.7 cm).WCs of the moderate and heavy smokers had an increase along with the increase of WCs beyond the 85 percentiles (WC=89.9 cm).Conclusion The effect of smoking status and BMI (WC) were inconsistent,however,with BMI and WC increased among the subjects whose BMI or WC were at the high extreme end of the distribution.Thus,we should advise the obese subjects to quit smoking.

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