1.ATF3 regulates inflammatory response in atherosclerotic plaques in mice through the NF-κB signaling pathway.
Bing XIA ; Jin PENG ; Jiuyang DING ; Jie WANG ; Guowei TANG ; Guojie LIU ; Yun WANG ; Changwu WAN ; Cuiyun LE
Journal of Southern Medical University 2025;45(6):1131-1142
OBJECTIVES:
To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression.
METHODS:
Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling.
RESULTS:
In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway.
CONCLUSIONS
AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals
;
Activating Transcription Factor 3/metabolism*
;
Signal Transduction
;
NF-kappa B/metabolism*
;
Humans
;
Mice
;
Plaque, Atherosclerotic/metabolism*
;
Inflammation/metabolism*
;
Apolipoproteins E
;
Atherosclerosis/metabolism*
;
Diet, High-Fat
2.Age-Related Changes of Biomechanical Properties for Limb Bones in Male Rats
Lin YANG ; Man LI ; Jiang HUANG ; Jie WANG ; Bing XIA ; Jiuyang DING ; Cuiyun LE ; Mingjie LI ; Zhengdong LI ; Jiawen WANG
Journal of Medical Biomechanics 2023;38(1):E170-E175
Objective To investigate the age-related changes of biomechanical properties for humerus, femur and tibia in male rats and their application values in age estimation. Methods According to different weeks of age, 90 healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52, 78 and 104-week groups with 10 rats in eachgroup. After the rats were executed by excessive anesthesia, humerus, femur, and tibia were separated and the attached soft tissues were removed. The length of the above-mentioned bones and the diameter of the middle section (compression site) were measured with vernier caliper, and the three-point bending test was conducted with electronic universal material testing machine to detect the ultimate load and displacement under ultimate load. Results There were significant differences in the ultimate load of humerus, femur and tibia among male rats in different age groups (P<0. 05). With the increase of week age, the ultimate loads of the humerus, femur and tibia increased first and then decreased, and reached the peak value in 52-week age group, showing a strong positive correlation with week age before 52 weeks ( r = 0. 884,0. 933,0. 929, P<0. 05). There was no significant difference in humerus and tibia. The displacement of femur under ultimate load was weakly positively correlated with week age (R= 0. 406,P<0. 05). The age prediction accuracy for automatic linear modeling of ultimate load for humerus, femur, tibia and three above-mentioned bones in rats before 52-week age was 78. 2% , 86. 8% , 84. 1% and 88. 3% , respectively. There was a strong positive correlation between the length of humerus, femur and tibia and the ultimate load (R= 0. 904, 0. 897, 0. 814, P<0. 05). The diameters of humerus, femur and tibia were strongly positively correlated with the ultimate load (R = 0. 759, 0. 814 and 0. 745, P<0. 05). Conclusions The ultimate loads of humerus, femur and tibia in male rats increased first and then decreased with age, and were positively correlated with age before 52 weeks, which could be used for age inference. The highest accuracy of age estimation was ultimate loads of three bones, followed by femur. The length/ middle diameter of humerus, femur and tibia were strongly positively correlated with the ultimate load.
3.Exploration and practice of holistic medicine and integrated medicine in the teaching of forensic pathological cause analysis of deaths
Jiawen WANG ; Jiang HUANG ; Jie WANG ; Bing XIA ; Dian WANG ; Changwu WAN ; Cuiyun LE ; Wenxin WU ; Xiaojun YU
Chinese Journal of Medical Education Research 2022;21(10):1329-1332
Based on the characteristics of forensic pathology, this paper explains the concept, connotation and advantages of holistic medicine and integrated medicine in the teaching of forensic pathology. Then, through the introduction of the specific teaching process design and effect analysis of the death cause analysis practical cases, it clarifies the necessity and effectiveness of integrated medicine and holistic medicine in the teaching of forensic pathology, and provides new ideas for the reform of the overall teaching of forensic pathology.
4.Curriculum design and lesson plan compilation of PBL teaching in forensic pathology
Cuiyun LE ; Bing XIA ; Jiawen WANG ; Zhu LI ; Jie WANG ; Changwu WAN
Chinese Journal of Medical Education Research 2021;20(11):1287-1291
Causes analysis of death is the most common work in forensic pathology practice. When designing problem-based learning (PBL) teaching objectives, we should take cause analysis of death as the main line and give consideration to other related issues. The selected cases should be typical ones that solve the target problems, which can fully reflect the basic theoretical knowledge of forensic pathology, and have moderate difficulty, delights and clear conclusions. The PBL course is divided into three steps. The first step focuses on providing students with case information to guide them to find out the problems that need to be solved. The second step focuses on discussing the problems and making pathological diagnoses. The third step focuses on answering the question raised at the beginning of the course. Each lesson can also be divided into several sections by which the lesson plans should be prepared. In the teaching process, performing active interaction with students, controlling the direction of classroom development, balancing student opportunities should be done well in order to make the curriculum smoothly and achieve the purpose of teaching.

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