1.A prediction model for high-risk cardiovascular disease among residents aged 35 to 75 years
ZHOU Guoying ; XING Lili ; SU Ying ; LIU Hongjie ; LIU He ; WANG Di ; XUE Jinfeng ; DAI Wei ; WANG Jing ; YANG Xinghua
Journal of Preventive Medicine 2025;37(1):12-16
Objective:
To establish a prediction model for high-risk cardiovascular disease (CVD) among residents aged 35 to 75 years, so as to provide the basis for improving CVD prevention and control measures.
Methods:
Permanent residents aged 35 to 75 years were selected from Dongcheng District, Beijing Municipality using the stratified random sampling method from 2018 to 2023. Demographic information, lifestyle, waist circumference and blood biochemical indicators were collected through questionnaire surveys, physical examinations and laboratory tests. Influencing factors for high-risk CVD among residents aged 35 to 75 years were identified using a multivariable logistic regression model, and a prediction model for high-risk CVD was established. The predictive effect was evaluated using the receiver operating characteristic (ROC) curve.
Results:
A total of 6 968 individuals were surveyed, including 2 821 males (40.49%) and 4 147 females (59.51%), and had a mean age of (59.92±9.33) years. There were 1 155 high-risk CVD population, with a detection rate of 16.58%. Multivariable logistic regression analysis showed that gender, age, smoking, central obesity, systolic blood pressure, fasting blood glucose, triglyceride and low-density lipoprotein cholesterol were influencing factors for high-risk CVD among residents aged 35 to 75 years (all P<0.05). The area under the ROC curve of the established prediction model was 0.849 (95%CI: 0.834-0.863), with a sensitivity of 0.693 and a specificity of 0.863, indicating good discrimination.
Conclusion
The model constructed by eight factors including demographic characteristics, lifestyle and blood biochemical indicators has good predictive value for high-risk CVD among residents aged 35 to 75 years.
2.Exploring Academic Characteristics of Contemporary Experts and Schools in Traditional Chinese Medicine Gynecology in Treating Endometriosis Diseases Based on SrTO
Zhiran LI ; Xiaojun BU ; Xiaodan WANG ; Le ZHANG ; Ruixue LIU ; Jingyu REN ; Xing LIAO ; Weiwei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):249-259
ObjectiveStarting from the etiology, pathogenesis, and treatment strategies of endometriosis and adenomyosis, to integrate and sort out the academic characteristics of contemporary renowned experts and schools in the field of traditional Chinese medicine gynecology. MethodsAccording to the systematic review of text and opinion (SrTO) process developed by the Joanna Briggs Institute (JBI) in Australia, this paper determined literature screening criteria by searching China National Knowledge Infrastructure (CNKI), VIP, Wanfang, and China Biomedical Literature Database. Information was extracted after literature screening, and quality evaluation was conducted using the JBI Narrative, Text, and Opinion Systematic Review Strict Evaluation Checklist. The JBI Narrative, Opinion, Text Evaluation, and Review Tool Summary Table was used for information synthesis, and data analysis and display were conducted in the form of text and charts. ResultsThe 146 articles related to 39 renowned experts and 19 articles related to 10 schools of thought were included. Research has found that contemporary experts and schools in traditional Chinese medicine gynecology consider blood stasis as the core pathogenesis in understanding the etiology and pathogenesis of two diseases and related infertility. Their viewpoints varied from multiple aspects such as clinical symptom characteristics, meridian circulation location, pathological product evolution, disease duration, emotional psychology, lifestyle habits, preference for food and drink, innate endowment, and acquired injury. In terms of treatment, it was advocated to divide the stage, treat according to different types, adapt to the times, integrate nature and humans, and combine multiple methods to treat comprehensively when necessary. It was also recommended to skillfully use insects, make good use of classic formulas and small prescriptions, pay attention to protecting the spleen and stomach and regulating emotions, and make good use of self-formulated empirical formulas for internal or external use. Besides, individualized long-term management of patients was also advocated. ConclusionThis study applies the SrTO process to systematically summarize the academic ideas of contemporary renowned experts and schools in traditional Chinese medicine gynecology regarding the causes, mechanisms, diagnosis, and treatments of endometriosis, providing a scientific and standardized reference for future theoretical exploration.
3.Enzyme-directed Immobilization Strategies for Biosensor Applications
Xing-Bao WANG ; Yao-Hong MA ; Yun-Long XUE ; Xiao-Zhen HUANG ; Yue SHAO ; Yi YU ; Bing-Lian WANG ; Qing-Ai LIU ; Li-He ZHANG ; Wei-Li GONG
Progress in Biochemistry and Biophysics 2025;52(2):374-394
Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.
4.PTPRD demethylation regulates the proliferation, migration, and chemoresistance of gastric cancer cells through the PI3K/Akt/mTOR pathway
LIU Yanhuia,b ; GAO Ziyua ; REN Pengb ; DU Yuxinb ; LIU Caixiaa ; XING Zhiweia
Chinese Journal of Cancer Biotherapy 2025;32(1):48-55
[摘 要] 目的:探究蛋白酪氨酸磷酸酶D(PTPRD)去甲基化通过PI3K/Akt/mTOR通路对胃癌细胞增殖、迁移及化疗耐药性的影响。方法:体外培养胃癌细胞MKN-74、MKN-45和人胃黏膜上皮细胞GES-1并检测PTPRD表达。常规培养MKN-45细胞及耐药MKN-45/5-FU细胞,分别转染PTPRD空载体(NC组、NC/5-FU组)、PTPRD过表达腺病毒(PTPRD组、PTPRD/5-FU组)、shRNA空载体(sh-NC组、sh-NC/5-FU组)、shRNA-PTPRD慢病毒(sh-PTPRD组、sh-PTPRD/5-FU组)和PTPRD过表达腺病毒 + 10 μmol/L 740Y-P处理(PTPRD + 740Y-P组、PTPRD + 740Y-P/5-FU组)。MTT法、划痕愈合实验检测各组细胞的增殖活力和迁移能力,细胞自噬实验检测细胞的自噬水平,WB法检测细胞中EMT和PI3K/Akt/mTOR通路相关蛋白的表达。采用0、2.5、5、10、20、40 μmol/L的5-aza处理MKN-45细胞,qPCR法、MTT法检测细胞中PTPRD mRNA表达和细胞增殖活力。结果:PTPRD mRNA和蛋白在胃癌细胞中均呈低表达(P < 0.05)。与MKN-45组相比,PTPRD组自噬体与自噬溶酶体数量、PTPRD、上皮钙黏素(E-cadherin)、BAX蛋白表达均增加(均P < 0.05),细胞增殖活力、细胞迁移率、p-PI3K、波形蛋白(vimentin)、p-Akt、p-mTOR蛋白表达均降低(均P < 0.05),sh-PTPRD组细胞增殖活力、细胞迁移率、p-PI3K、vimentin、p-Akt、p-mTOR蛋白表达均增加(均P < 0.05),自噬体与自噬溶酶体数量、PTPRD、E-cadherin、BAX蛋白表达均减少(均P < 0.05);与PTPRD组相比,PTPRD + 740Y-P组细胞增殖活力、细胞迁移率、p-PI3K、vimentin、p-Akt、p-mTOR蛋白表达均增加(均P < 0.05),自噬体与自噬溶酶体数量、PTPRD、E-cadherin、BAX蛋白表达减少(均P < 0.05)。随着5-aza浓度的增加,MKN-45细胞中PTPRD mRNA表达增加、细胞增殖活力均降低(均P < 0.05)。与MKN-45/5-FU组相比,PTPRD/5-FU组细胞迁移率、细胞增殖活力均降低(均P < 0.05),sh-PTPRD/5-FU组细胞迁移率、细胞增殖活力均增加(均P < 0.05);与PTPRD/5-FU组相比,PTPRD + 740Y-P/5-FU组细胞迁移率、细胞增殖活力均增加(均P < 0.05)。结论:PTPRD在胃癌细胞中呈低表达状态,PTPRD去甲基化可能通过抑制PI3K/Akt/mTOR信号通路抑制胃癌细胞增殖、迁移并增强其对化疗的敏感性。
5.Constructing a model of degenerative scoliosis using finite element method:biomechanical analysis in etiology and treatment
Kai HE ; Wenhua XING ; Shengxiang LIU ; Xianming BAI ; Chen ZHOU ; Xu GAO ; Yu QIAO ; Qiang HE ; Zhiyu GAO ; Zhen GUO ; Aruhan BAO ; Chade LI
Chinese Journal of Tissue Engineering Research 2025;29(3):572-578
BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.
6.A network meta-analysis on therapeutic effect of different types of exercise on knee osteoarthritis patients
Jia LI ; Qianru LIU ; Mengnan XING ; Bo CHEN ; Wei JIAO ; Zhaoxiang MENG
Chinese Journal of Tissue Engineering Research 2025;29(3):608-616
OBJECTIVE:The main clinical manifestations of knee osteoarthritis are pain,swelling,stiffness,and limited activity,which have a serious impact on the life of patients.Exercise therapy can effectively improve the related symptoms of patients with knee osteoarthritis.This paper uses the method of network meta-analysis to compare the efficacy of different exercise types in the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Embase,Cochrane Library,Web of Science,Scopus,Ebsco,SinoMed,and UpToDate were searched with Chinese search terms"knee osteoarthritis,exercise therapy"and English search terms"knee osteoarthritis,exercise".Randomized controlled trials on the application of different exercise types in patients with knee osteoarthritis from October 2013 to October 2023 were collected.The outcome measures included visual analog scale,Western Ontario and McMaster Universities Osteoarthritis Index score,Timed Up and Go test,and 36-item short form health survey.Literature quality analysis was performed using the Cochrane Manual recommended tool for risk assessment of bias in randomized controlled trials.Two researchers independently completed the data collection,collation,extraction and analysis.RevMan 5.4 and Stata 18.0 software were used to analyze and plot the obtained data. RESULTS:A total of 29 articles with acceptable quality were included,involving 1 633 patients with knee osteoarthritis.The studies involved four types of exercise:aerobic training,strength training,flexibility/skill training,and mindfulness relaxation training.(1)The results of network meta-analysis showed that compared with routine care/health education,aerobic training could significantly improve pain symptoms(SMD=-3.26,95%CI:-6.33 to-0.19,P<0.05);strength training(SMD=-0.79,95%CI:-1.34 to-0.23,P<0.05)and mindfulness relaxation training(SMD=-0.79,95%CI:-1.23 to-0.34,P<0.05)could significantly improve the function of patients.Aerobic training(SMD=-1.37,95%CI:-2.24 to-0.51,P<0.05)and mindfulness relaxation training(SMD=-0.41,95%CI:-0.80 to-0.02,P<0.05)could significantly improve the functional mobility of patients.Mindfulness relaxation training(SMD=0.70,95%CI:0.21-1.18,P<0.05)and strength training(SMD=0.42,95%CI:0.03-0.81,P<0.05)could significantly improve the quality of life of patients.(2)The cumulative probability ranking results were as follows:pain:aerobic training(86.6%)>flexibility/skill training(60.1%)>strength training(56.8%)>mindfulness relaxation training(34.7%)>routine care/health education(11.7%);Knee function:strength training(73.7%)>mindfulness relaxation training(73.1%)>flexibility/skill training(56.1%)>aerobic training(39.9%)>usual care/health education(7.6%);Functional mobility:aerobic training(94.7%)>mindfulness relaxation training(65.5%)>strength training(45.1%)>flexibility/skill training(41.6%)>routine care/health education(3.2%);Quality of life:mindfulness relaxation training(91.3%)>strength training(68.0%)>flexibility/skill training(44.3%)>aerobic training(34.0%)>usual care/health education(12.3%). CONCLUSION:(1)Exercise therapy is effective in the treatment of knee osteoarthritis,among which aerobic training has the best effect on relieving pain and improving functional mobility.Strength training and mindfulness relaxation training has the best effect on improving patients'function.Mindfulness relaxation training has the best effect on improving the quality of life of patients.(2)Limited by the quality and quantity of the included literature,more high-quality studies are needed to verify it.
7.Different exercise modalities promote functional recovery after peripheral nerve injury
Xiaoxuan ZHAO ; Shuaiyi LIU ; Qi LI ; Zheng XING ; Qingwen LI ; Xiaolei CHU
Chinese Journal of Tissue Engineering Research 2025;29(6):1248-1256
BACKGROUND:Exercise as a form of active rehabilitation can improve the dysfunction caused by peripheral nerve injury,and different exercise modalities target different lesion sites and recovery mechanisms. OBJECTIVE:To comprehensively analyze the application and mechanisms of different exercise modalities in functional recovery from peripheral nerve injury. METHODS:A computerized search was conducted in PubMed and CNKI databases for relevant literature published before January 2024.The search terms used were"peripheral nerve injury,spinal cord,exercise,cerebral cortex,muscle atrophy,mirror therapy,blood flow restriction training"in both English and Chinese.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Peripheral nerve injury can cause systemic pathological changes such as skeletal muscle atrophy,corresponding spinal cord segmental lesions,and sensorimotor cortex remodeling.Aerobic exercise can improve dysfunction by enhancing the immune response,promoting glial cell polarization,and promoting the release of nerve growth factor.Blood flow restriction exercise can regulate the secretion of muscle growth factor,promote muscle growth and enhance muscle strength.Mirror movement has a good effect in activating the cerebral cortex and reducing cortical remodeling.Different exercise modalities have potential benefits in functional recovery after peripheral nerve injury;however,there are still some problems and challenges,such as the choice of exercise modalities,the control of exercise intensity and frequency,and the detailed analysis of mechanisms.
8.Development and application of a three-dimensional digital visualization system for children's neck acupoints
Xiaojing AO ; Kun LI ; Yuhang LIU ; Xiaoxuan YANG ; Xing WANG ; Zhijun LI ; Xiaoyan REN ; Shaojie ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1834-1840
BACKGROUND:Currently,there have been studies on three-dimensional digitalization and visualization systems for adult acupoints,but there are not many reports on the visualization of pediatric acupoints based on real pediatric digital sectional anatomical datasets. OBJECTIVE:To design and develop a digital three-dimensional visualization system for children's neck acupoints,to provide a basis for acupuncture and moxibustion,meridian and acupoint science teaching,clinical practice,acupuncture manipulation practice,and acupuncture safety research,and to provide a basis for the development of children's acupoint simulation system. METHODS:Based on a real cross-sectional anatomical dataset of pre-school boys,a three-dimensional digital virtual anatomical model of the neck region of children and internal multi-organ three-dimensional reconstruction were completed using PhotoShop 2021 and Digihuman Reconstruction System software.A database of 11 acupoints was compiled,including Fengfu and Fengchi,using the Unity database language.A three-dimensional model of children's neck anatomy,acupoint database,and writing acupuncture operation codes were integrated in Unity3D software.A three-dimensional digital visualization system for children's neck acupoints was successfully created,which integrated simulation acupoint positioning,three-dimensional acupoint anatomy,acupuncture training,clinical teaching,and acupuncture safety research. RESULTS AND CONCLUSION:(1)This study was based on real child specimens.Manual layer by layer segmentation of cross-sectional images was used to ensure the accuracy of the three-dimensional model to the greatest extent possible.The 3D software Digihuman Reconstruction System was utilized to extract and save independent segmentation data.PhotoShop 2021 software was collaborated with to complete dozens of three-dimensional reconstruction anatomical models of the outer skin of the neck and its internal bone structure,cervical spinal cord,blood vessels and nerves,muscles,and ligaments in children.The basic morphology and overall contour integrity verification of each independent structure were completed in MeshLab software.The 3-material research 13.0 software was applied for final fine tuning and anatomical position confirmation,successfully simulating and restoring the true anatomical morphology of the neck of preschool children.(2)Based on and referring to the national standards of the People's Republic of China,a database of commonly used acupoints in children's neck region was collected and organized,including their names,meridians,positioning,local anatomy,needle insertion levels,acupuncture methods,acupuncture accidents and prevention,acupoint indications,and two-dimensional anatomical sectional images.(3)Unity3D software was employed to integrate the three-dimensional model of children's neck,acupuncture simulation operation,and acupoint database,and a three-dimensional digital children's neck acupoint acupuncture visualization system was successfully constructed.The system displayed information on children's neck acupoints,two-dimensional and three-dimensional anatomical structures,and achieved two-dimensional and three-dimensional acupuncture simulation functions and acupuncture safety research functions for children's neck acupoints.Based on the ultra-thin sectional anatomical dataset of real child specimens,the first three-dimensional digital and visualization system for acupoints in the neck region of children had been constructed.Compared with previous acupoint acupuncture systems,it is more in line with the anatomical and morphological development characteristics of Asian children and has high application value in the fields of acupuncture safety research,clinical teaching,and acupuncture simulation training.
9.Effect of Tongmai Kaiqiao Pills on Mitochondrial Biogenesis of Hippocampal Neurons in Rats with Vascular Cognitive Impairment Based on AMPK/PGC-1α Signaling Pathway
Luyao MA ; Yanjie LI ; Haoyuan LIU ; Yanjie BAI ; Ruoxing XING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):125-134
ObjectiveTo observe the effects of Tongmai Kaiqiao pills on AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) signaling pathway and mitochondrial biogenesis in hippocampal tissue of rats with vascular cognitive impairment (VCI) and to investigate the potential mechanism of Tongmai Kaiqiao pills in improving cognitive impairment in rats with VCI. MethodsTwelve of 72 male SD rats were selected as the sham operation group, and the remaining rats were modelled using the modified 2VO method. The rats that were successfully modelled were divided into the model group, the high-dose group of Tongmai Kaiqiao pills (27.6 g·kg-1), the low-dose group of Tongmai Kaiqiao pills (13.8 g·kg-1), the combination group (27.6 g·kg-1 Tongmai Kaiqiao pills + 25 mg·kg-1 dorsomorphin), and the donepezil hydrochloride group (0.45 g·kg-1) according to the random number table method. After four weeks of continuous intraperitoneal injection of the corresponding drugs, the Morris water maze test was used to test the learning and memory ability of rats. Hematoxylin-eosin (HE) staining and Nissl staining were used to detect pathological changes in the hippocampus of the rats. The content of mitochondrial adenosine triphosphate (ATP) in the brain hippocampus was detected by colorimetry, and reactive oxygen species (ROS) level was detected in rat mitochondria by MitoSOX Red assay. Mitochondrial DNA copy number was detected by real-time fluorescent quantitative PCR (Real-time PCR). Pathological changes in mitochondria were observed by transmission electron microscopy (TEM), and AMPK, PGC-1α, phosphorylated AMP-activated protein kinase (p-AMPK), nuclear respiratory factor 1 (Nrf1), and mitochondrial transcription factor A (TFAM) protein expression in the hippocampus of the rats were detected by Western blot. ResultsCompared with those in the sham operation group, rats in the model group had a reduced number of platform crossings (P<0.01), significantly prolonged evasion latency (P<0.01), disorganized neuronal arrangement in the hippocampal region, widened gaps, and blurred nucleus membrane and nucleolus boundaries. The emergence of necrotic cells was visible. The color of the nissl bodies was light, and the number was reduced with severe loss. Mitochondria were atrophied, and cristae were lost. Severe damage was observed. The content of ROS was increased, and the level of ATP was decreased. mtDNA copy number decreased significantly (P<0.01), and the protein expression of p-AMPK, PGC-1α, Nrf1, and TFAM decreased (P<0.05, P<0.01). Compared with those in the model group, rats in the high-dose group of Tongmai Kaiqiao pills and donepezil hydrochloride group showed a shorter time to find the platform (P<0.01), increased number of platform crossings (P<0.01), restored mitochondrial morphology and structure of the hippocampal neurons, alleviated neuronal death, increased number of nissl bodies, weaken degree of injury, lower content of ROS, and significantly increased levels of ATP and number of copies of mtDNA (P<0.05, P<0.01). In addition, there was increased protein expression of p-AMPK, PGC-1α, Nrf1, and TFAM (P<0.05, P<0.01). Compared with the model group, the evasion latency was shortened in the low-dose group of Tongmai Kaiqiao pills (P<0.01), and the number of platform crossings was increased, but the difference was not statistically significant. The mitochondria were swollen and deformed, and the cristae became shorter and partially disappeared. The degree of damage did not improve significantly, and the number of nissl bodies was increased but not statistically significant. The ROS content decreased (P<0.01), but there was no significant difference in ATP level and mtDNA copy number. The protein expression of PGC-1α was increased (P<0.05), but there was no significant difference in the protein expression of p-AMPK, Nrf1, and TFAM, and the results were not statistically significant. Compared with the donepezil hydrochloride group, there was no significant change in the results of each assay in the high-dose group of Tongmai Kaiqiao pills, and the difference was not statistically significant. Compared with the high-dose group of Tongmai Kaiqiao pills, rats in the combination group had a significantly lower number of platform crossings (P<0.01), a significantly longer evasion latency (P<0.01), a reduced number of neuronal cells, disorganized tissue structure, swollen and blurred cell outlines, a significant reduction in the number of nissl bodies. Moreover, there was an increase in the content of ROS, a decrease in the level of ATP and the number of mtDNA copies (P<0.01), and a decrease in the expression of p-AMPK, PGC-1α, Nrf1, and TFAM (P<0.05). ConclusionTongmai Kaiqiao pills is able to improve cognitive function in rats by activating the AMPK/PGC-1α signaling pathway, promoting mitochondrial biogenesis, and attenuating pathological damage to neurons in the hippocampal region, thereby demonstrating its therapeutic potential.
10.NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
Yumin QIU ; Xi CHEN ; Jianning ZHANG ; Zhangchi LIU ; Qiuxia ZHU ; Meixin ZHANG ; Jun TAO ; Xing WU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):70-80
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group (Saline) and hypertension group (Ang Ⅱ, which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps), and supplemented daily with nicotinamide mononucleotide (300 mg/kg), a precursor of NAD+. Blood pressure, endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA, SIRT3 and isocitrate dehydrogenase 2 (IDH2). 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS, eNOS, SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure (P<0.001) and improved endothelial function and arterial stiffness (P<0.001) in hypertensive mice. In vitro, NMN improved endothelial function in AngII-stimulated endothelial cells (P<0.05) and attenuated mitochondrial oxidative stress levels (P<0.001). Mechanistically, NMN elevated SIRT3 activity (P<0.001), which subsequently enhanced IDH activity (P<0.001) and reduced oxidative stress levels in endothelial cells. Conversely, knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function (P<0.001). ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.


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