1.Mitochondria: The Target of Ionizing Radiation Damage
Lian-Chen TIAN ; Ya-Yi YUAN ; Xu-Hong DANG
Progress in Biochemistry and Biophysics 2025;52(4):836-844
In recent years, due to the development of radiotherapy technology and nuclear energy, people have paid more and more attention to the various effects of ionizing radiation on organisms. Ionizing radiation can induce protein, DNA and other biological macromolecules to damage, resulting in apoptosis, senescence, cancer and a series of changes. For a long time, it has been believed that the main target of ionizing radiation damage is DNA in the nucleus. However, it has been reported in recent years that ionizing radiation has both direct and indirect effects, and the theory of ROS damage in the indirect effects believes that ionizing radiation has target uncertainty, so it is not comprehensive enough to evaluate only the DNA damage in the nucleus. It has been reported that ionizing radiation can cause damage to organelles as well as damage to cells. Mitochondria are important damaged organelles because mitochondria occupy as much as 30% of the entire cell volume in the cytoplasm, which contains DNA and related enzymes that are closely related to cellular ATP synthesis, aerobic respiration and other life activities. What is more noteworthy is that mitochondria are the only organelles in which DNA exists in the human body, which makes researchers pay attention to various damage to mitochondrial DNA caused by ionizing radiation (such as double-strand breaks, base mismatching, and fragment loss). Although these damages also occur in the nucleus, mitochondrial DNA is more severely damaged than nuclear DNA due to its lack of histone protection, so mitochondria are important targets of ionizing radiation damage in addition to the nucleus. Mitochondrial DNA is not protected by histones and has little repair ability. When exposed to ionizing radiation, common deletions occur at an increased frequency and are passed on to offspring. For large-scale mitochondrial DNA damage, mitochondria indirectly compensate for the amount of damaged DNA by increasing the number of DNA copies and maintaining the normal function of mitochondrial DNA. Mitochondria are in a state of oxidative stress after exposure to ionizing radiation, and this oxidative stress will promote the change in mitochondrial function. When mitochondria are damaged, the activity of proteins related to aerobic respiration decreases, and oxidative respiration is inhibited to a certain extent. At the same time, a large amount of active superoxide anions are continuously produced to stimulate mitochondrial oxidative stress, and the signal of such damage is transmitted to the surrounding mitochondria, resulting in a cascade of damage reaction, which further activates the signalling pathway between mitochondria and nucleus. The cell nucleus is also in a state of oxidative stress, and finally, the level of free radicals is high, causing secondary damage to the genetic material DNA of mitochondria and nucleus. In this paper, the damage effects of ionizing radiation on mitochondria are reviewed, to provide a new idea for radiation protection.
2.Comparison of small-sample multi-class machine learning models for plasma concentration prediction of valproic acid
Xi CHEN ; Shen’ao YUAN ; Hailing YUAN ; Jie ZHAO ; Peng CHEN ; Chunyan TIAN ; Yi SU ; Yunsong ZHANG ; Yu ZHANG
China Pharmacy 2025;36(11):1399-1404
OBJECTIVE To construct three-class (insufficient, normal, excessive) and two-class (insufficient, normal) models for predicting plasma concentration of valproic acid (VPA), and compare the performance of these two models, with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 (a total of 695 sets of data). In this study, predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation, and the performance of the models was evaluated using three indexes: accuracy, F1 score, and the area under the working characteristic curve of the subject (AUC). RESULTS XGBoost feature importance scores revealed that in the three-class model, the importance ranking of kidney disease and electrolyte disorders was higher. However, in the two-class model, the importance ranking of these features significantly decreased, suggesting a close association with the excessive blood concentration of VPA. In the three-class model, Random Forest method performed best, with F1 score of 0.704 0 and AUC of 0.519 3 on the test set; while in the two-class model, CatBoost method performed optimally, with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration, but its prediction and model generalization abilities are poor; the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases, but its model performance is stronger.
3.Longitudinal cross lagged analysis of body mass index and weight stigma with depressive symptom in adolescents
DONG Ziqi, SONG Xinli, YUAN Wen, LI Jing, YANG Tian, ZHANG Xiuhong, SONG Yi, DONG Yanhui
Chinese Journal of School Health 2025;46(9):1242-1245
Objective:
To explore the bidirectional associations among body mass index Z scores (BMI Z scores) and weight stigma with depressive symptoms in adolescents, thereby providing evidence for targeted intervention strategies.
Methods:
A stratified cluster random sampling method was employed to select 18 301 adolescents aged 12-18 years from all 12 prefectures (103 counties) in the Inner Mongolia Autonomous Region, and two waves of longitudinal surveys were conducted in September 2023 (T1) and September 2024 (T2) among the adolescents. Weight stigma was assessed by using a self developed questionnaire, depressive symptom was measured with the Center for Epidemiologic Studies Depression Scale (CES-D), and BMI Z scores were calculated according to the World Health Organization standards. Pearson correlation analysis was used to examine associations among variables, and cross lagged panel models were constructed to investigate the dynamic bidirectional relationships among the three variables.
Results:
Adolescents BMI Z scores and weight stigma with depressive symptoms all exhibited autoregressive stability across the two time points (autoregressive paths, all P <0.01). Cross lagged model comparisons indicated that the bidirectional path model achieved the best fit ( χ 2=12.65, RMSEA =0.017, CFI =1.000; △ χ 2=193.39, P <0.01), supporting dynamic bidirectional associations among the three variables. After adjusting for gender, age, subjective social status and only child status, T1 BMI Z scores among adolescents positively predicted T2 weight stigma ( β =0.061), and T1 weight stigma positively predicted T2 depressive symptoms ( β =0.608); in the reverse direction, T1 depressive symptoms predicted T2 weight stigma ( β =0.003), and T1 weight stigma predicted T2 BMI Z scores ( β =0.081) (all P <0.01).
Conclusions
There is a bidirectional cross lagged relationship among adolescents BMI Z scores and weight stigma with depressive symptoms, suggesting that weight stigma may serve as a key psychological variable linking obesity and depressive symptoms. Greater attention should be paid to the potential threat of weight stigma to adolescents mental health, with intervention strategies expanded from a solely physiological focus to encompass psychosocial dimensions.
4.Cloning and gene functional analysis study of dynamin-related protein GeDRP1E gene in Gastrodia elata
Xin FAN ; Jian-hao ZHAO ; Yu-chao CHEN ; Zhong-yi HUA ; Tian-rui LIU ; Yu-yang ZHAO ; Yuan YUAN
Acta Pharmaceutica Sinica 2024;59(2):482-488
The gene
5.Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors
Yue LI ; Guo-qing LI ; Yuan-yuan TIAN ; Cong-ran LI ; Xin-yi YANG ; Kai-hu YAO ; Xue-fu YOU
Acta Pharmaceutica Sinica 2024;59(2):279-288
The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non
6.Exploration of the Acupoint Selection Rules of Acupuncture for the Treatment of Tic Disorders in Children Based on Data Mining Techniques
Shan-Hong WU ; Zi-Han GONG ; Yan WANG ; Yang GAO ; Yi-Ming YUAN ; Ming-Yue ZHAO ; Zi-Wei ZHANG ; Tian-Yi LI ; Fei PEI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):1083-1090
Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.
7.Mechanism of BMAL1 attenuating H2O2-induced cardiomyocyte injury
Na YI ; Wen XIAO ; Yuan TIAN ; Lili YUAN
Tianjin Medical Journal 2024;52(2):119-123
Objective To investigate the effect of BMAL1 on H2O2-induced cardiomyocyte injury through NRF2-regulated ROS/NLRP3 inflammasome pathway.Methods H9c2 cells and H9c2 cells with stable over-expressed BMAL1 were cultured and divided into the control group,the H2O2 group,the BMAL1-OE group,the BMAL1-OE+H2O2 group,the BMAL1-OE+ML385 group and the BMAL1-OE+ML385+H2O2 group.All groups were pre-intervened with corresponding inhibitors,and then treated with 0.2 mmol/L H2O2,except for the control group and the BMAL1-OE group.After the intervention,CCK-8 assay was used to measure cell viability,fluorescent probe DCFH-DA was used to measure ROS generation and Western blot assay was used to detect BMAL1,NRF2 and NLRP3 protein expressions.ELISA was used to determine IL-1β release.Results Compared with the control group,the cell viability was decreased,ROS generation was increased,BMAL1 and NRF2 protein expressions were decreased,NLRP3 expression and IL-1β release were increased in the H2O2 group(P<0.05).Compared with the H2O2 group,the cell viability was increased,ROS generation was decreased,BMAL1-OE and NRF2 protein expressions were increased,NLRP3 expression and IL-1β release were decreased in the BMAL1-OE+H2O2 group(P<0.05).Compared with the BMAL1-OE+H2O2 group,the cell viability was decreased,ROS generation was increased,NLRP3 expression and IL-1β release were increased in the BMAL1-OE+ML385+H2O2 group(P<0.05).Conclusion BMAL1 attenuates H2O2-induced H9c2 cardiomyocyte injury,and its mechanism may be related to the regulation of ROS/NLRP3 inflammasome pathway through NRF2.
8.Correlation between age of menarche/first spermatozoa and obesity in urban and rural primary and secondary school students in Inner Mongolia
YANG Tian, SONG Yi, DONG Yanhui, YUAN Wen, ZHANG Xiuhong, FAN Yaochun, LI Huan, YUE Xuanzhi
Chinese Journal of School Health 2024;45(5):719-722
Objective:
To understand the pubertal development of primary and secondary school students in urban and rural areas of the Inner Mongolia Autonomous Region in 2021, so as to provide clues for further clarification of the health hazards of early pubertal initiation.
Methods:
From October to November 2021, primary and secondary school students in 12 provinces and cities of Inner Mongolia were selected by stratified cluster random sampling, including 21 662 girls who had reached menarche and 10 600 boys who had their first seminal emission, as well as 46 183 girls who had not reached menarche and 78 995 boys who had not experienced their first seminal emission. The height and weight of the primary and secondary school students were measured, and the time of first seminal emission or menarche was recorded. The study used the Mann-Whitney U test to analyze the differences between urban and rural students, Spearmans rank correlation to analyze the correlation between overweight and obesity and the age of pubertal initiation, and the Logistic regression model to analyze the correlation between pubertal initiation and age of pubertal initiation.
Results:
The age of menarche for urban girls [(12.31±1.29) years old] was earlier than that of suburban girls [(12.43±1.24) years old], and the age of first spermatozoa for urban boys [(13.85±1.20) years old] was statistically significant compared with that of suburban boys [(13.79±1.36) years old] (t=12.76, 10.58, P<0.05). There was a negative correlation between the age of menarche and overweight/obesity among girls aged 10-14 years (r=-0.169, P<0.05), and there was no statistically significant correlation between the age of spermarche and overweight/obesity in boys aged 5-9, 10-14, and 15-20 years (r=0.122, -0.022, -0.004, P>0.05). The occurrence of menarche in overweight girls was 1.06(95%CI=1.01-1.11) times higher than that in the normal group, and 1.13(95%CI=1.06-1.20) times higher among obese girls than normalweight girls. Compared to urban areas, primary and secondary school students in suburban counties observed the onset of puberty later [OR=0.88(95%CI=0.85-0.91) for menarche, OR=0.94(95%CI=0.89-0.99) for first spermatozoa] (P<0.05).
Conclusions
Obesity during childhood and adolescence is associated with earlier onset of puberty among female students in Inner Mongolia, and later onset of puberty among primary and secondary school students in suburban counties compared with those in urban areas.
9.Role of Guiqi Yiyuan ointment combined with cisplatin in the treatment of Lewis lung cancer based on PI3K/Akt/mTOR signal pathway
Chao YUAN ; Si-Qi KONG ; Jian-Qing LIANG ; Yi ZHANG ; Rong HU ; Yue ZHANG ; Yu LIU ; Jin-Tian LI
The Chinese Journal of Clinical Pharmacology 2024;40(10):1424-1428
Objective To observe the inhibitory effect of Guiqi Yiyuan ointment on tumor growth in mice with Lewis lung cancer,and to explore the molecular mechanism of Guiqi Yiyuan ointment combined with cisplatin through phosphoinositide 3-kinase/protein kinase B/mammalian rapamycin target protein(PI3K/Akt/mTOR)signal pathway.Methods Sixty C57BL/6 mice were randomly divided into 6 groups with 10 mice in each group.Except for the blank group(0.9%NaCl),Lewis lung cancer-bearing mice were randomly divided into model group(0.9%NaCl),control group(0.9%NaCl,cisplatin 5 mg·kg-1)and low,medium,high dose experimental groups(Guiqi Yiyuan ointment 1.6,3.3,6.6 g·kg-1,cisplatin 5 mg·kg-1).Flow cytometry was used to detect bone marrow-derived suppressor cells(MDSCs);the expression of related proteins in tumor tissues was detected by Western blot.Results The tumor inhibition rates in control group and low,medium,high dose experimental groups were(39.87±4.45)%,(45.74±14.97)%,(57.78±4.70)%and(69.82±11.05)%.The proportion of MDSCs in bone marrow of in blank group,model group,control group and low,medium,high dose experimental groups were(36.13±1.08)%,(68.63±2.94)%,(58.93±2.02)%,(58.00±1.50)%,(50.93±5.06)%and(43.07±2.41)%.The protein expressions of p-PI3K/PI3K in model group,control group and low,medium and high experimental groups were 0.97±0.03,0.77±0.02,0.72±0.01,0.68±0.03 and 0.53±0.02;PTEN were 0.21±0.07,0.65±0.07,0.74±0.06,0.99±0.13,1.11±0.13;p-Akt/Akt were 1.01±0.02,0.82±0.02,0.77±0.00,0.72±0.03 and 0.52±0.04;p-mTOR/mTOR were 1.01±0.01,0.76±0.05,0.69±0.07,0.59±0.06 and 0.47±0.06.There were significant differences between low,medium,high experimental groups and control group(all P<0.05).Conclusion Guiqi Yiyuan ointment combined with cisplatin can significantly improve the quality of life and inhibit tumor growth in mice.The mechanism may be the inhibition of PI3K/Akt/mTOR signal pathway and the enhancement of tumor cell apoptosis and autophagy.
10.Effects of Platycodon grandiflorum Bai powder in the treatment non-small cell lung cancer rats
Chao YUAN ; Jin-Tian LI ; Jian-Qing LIANG ; Yi ZHANG ; Si-Qi KONG ; Rong HU ; Yue ZHANG ; Yu LIU
The Chinese Journal of Clinical Pharmacology 2024;40(11):1608-1612
Objective To observe the effects of traditional Chinese medicine compound Platycodon grandiflorum Bai powder on the growth of subcutaneously implanted tumor and the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cysteinyl aspartate specific proteinase(caspase)-3 and caspase-9 in subcutaneously implanted tumor of Lewis lung cancer mice.Methods The model of transplanted tumor of Lewis lung cancer in mice was established.Seventy SPF male C57BL/6 mice were randomly divided into blank group,model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combined group.Blank group and model group were given 0.9%NaCl 0.2 mL by gavage;control group was given 0.9%NaCl by gavage and 25 mg·kg-1cisplatin intraperitoneally;high,medium,low dose experimental groups were given 193,96,48 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,respectively;combined group was given 96 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,and 25 mg·kg-1 cisplatin intraperitoneally,once every other day.The myelogenous suppressor cells(MDSCs)of mouse bone marrow were detected by flow cytometry,and the expressions of Bel-2,Bax,caspase-3 and caspase-9 in tumor cells were detected by immunofluorescence.Results The percentage of MDSCs in bone marrow of mice in blank group,model group,low dose experimental,medium,high dose experimental group,control group and combination group were(32.50±2.76)%,(63.13±3.14)%,(48.43±2.23)%,(42.53±1.28)%,(32.93±3.56)%,(51.30±4.25)%and(19.90±6.21)%,respectively.The fluorescence intensities of Bax in model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combination group were 10.42±0.68,12.40±1.23,15.14±0.65,22.95±1.76,27.18±1.62 and 31.61±1.28;Bel-2 were 36.85±0.80,33.92±4.20,28.88±1.01,20.04±2.21,15.69±2.36 and 6.05±0.73;caspase-3 were 5.28±0.44,7.63±0.55,9.66±0.85,14.73±1.18,17.95±1.29 and 22.92±1.95;caspase-9 were 9.48±0.90,11.57±0.72,13.45±0.93,15.73±1.44,19.20±0.96 and 23.21±1.51.There were significant differences between medium,high dose experimental groups and model group(all P<0.05),and there were significant differences between combined group and control group(all P<0.05).Conclusion Platycodon grandiflorum Bai powder can up-regulating the expression of Bax,caspase-3 and caspase-9,down-regulating the expression of Bel-2,inhibiting MDSCs,promoting tumor cell apoptosis and inhibiting tumor growth.


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