1.Exploring Mechanism of Yiqi Huoxue Jiedu Formula in Alleviating Immune Cell Exhaustion in Sepsis Based on Transcriptomics and Metabolomics
Rui CHEN ; Qiusha PAN ; Kaiqiang ZHONG ; Shuqi MA ; Wei HUANG ; Jiahua LAI ; Ruifeng ZENG ; Xiaotu XI ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):109-118
ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula(YHJF) on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated, model, low-dose YHJF(4.1 g·kg-1), and high-dose YHJF(8.2 g·kg-1) groups. Except for the sham-operated group, a cecal ligation and puncture(CLP) procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses, while the sham-operated and model groups received an equal volume of physiological saline. After the intervention, the 7-day survival rate of each group was recorded, and spleen samples were collected 72 h post-intervention, and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL) staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the levels of interleukin(IL)-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes(DEGs) and differential metabolites in the spleen, followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction(Real-time PCR), flow cytometry, and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice(P0.05). Compared with the sham-operated group, the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling, with markedly elevated peripheral serum IL-4 and IL-10 levels(P0.01). Compared with the model group, the high-dose YHJF group showed a reduction in apoptosis of spleen cells, an increase in the spleen index, and a significant decrease in peripheral serum IL-4 and IL-10 levels(P0.05). Spleen transcriptomics identified 255 DEGs between groups, potentially serving as intervention targets for YHJF. Gene Ontology(GO) enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer(NK) cell-mediated positive immune regulation, cell killing, cytokine production, positive regulation of innate immune cells, and interferon production. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear transcription factor-κB(NF-κB) signaling pathway. Protein-protein interaction(PPI) network analysis identified CD160, granzyme B(GZMB), and chemokine ligand 4(CCL4) as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention, and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism, arachidonic acid metabolism, glycosylphosphatidylinositol(GPI) anchor biosynthesis, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Verification results showed that, compared with the sham-operated group, the model group exhibited significantly elevated CD160 mRNA expression level in the spleen, along with markedly decreased CCL4 and GZMB mRNA expression, and had a significant increase in CD160 expression on the surface of natural killer T(NKT) cells in the spleen(P0.01). Compared with the model group, the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen, a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group, CD160 expression on the surface of splenic NKT cells in the model group was significantly increased(P0.01), while high-dose YHJF intervention significantly reduced CD160 expression(P0.01). ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160, and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.
2.Exploring Mechanism of Yiqi Huoxue Jiedu Formula in Alleviating Immune Cell Exhaustion in Sepsis Based on Transcriptomics and Metabolomics
Rui CHEN ; Qiusha PAN ; Kaiqiang ZHONG ; Shuqi MA ; Wei HUANG ; Jiahua LAI ; Ruifeng ZENG ; Xiaotu XI ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):109-118
ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula(YHJF) on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated, model, low-dose YHJF(4.1 g·kg-1), and high-dose YHJF(8.2 g·kg-1) groups. Except for the sham-operated group, a cecal ligation and puncture(CLP) procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses, while the sham-operated and model groups received an equal volume of physiological saline. After the intervention, the 7-day survival rate of each group was recorded, and spleen samples were collected 72 h post-intervention, and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL) staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the levels of interleukin(IL)-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes(DEGs) and differential metabolites in the spleen, followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction(Real-time PCR), flow cytometry, and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice(P0.05). Compared with the sham-operated group, the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling, with markedly elevated peripheral serum IL-4 and IL-10 levels(P0.01). Compared with the model group, the high-dose YHJF group showed a reduction in apoptosis of spleen cells, an increase in the spleen index, and a significant decrease in peripheral serum IL-4 and IL-10 levels(P0.05). Spleen transcriptomics identified 255 DEGs between groups, potentially serving as intervention targets for YHJF. Gene Ontology(GO) enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer(NK) cell-mediated positive immune regulation, cell killing, cytokine production, positive regulation of innate immune cells, and interferon production. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear transcription factor-κB(NF-κB) signaling pathway. Protein-protein interaction(PPI) network analysis identified CD160, granzyme B(GZMB), and chemokine ligand 4(CCL4) as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention, and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism, arachidonic acid metabolism, glycosylphosphatidylinositol(GPI) anchor biosynthesis, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Verification results showed that, compared with the sham-operated group, the model group exhibited significantly elevated CD160 mRNA expression level in the spleen, along with markedly decreased CCL4 and GZMB mRNA expression, and had a significant increase in CD160 expression on the surface of natural killer T(NKT) cells in the spleen(P0.01). Compared with the model group, the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen, a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group, CD160 expression on the surface of splenic NKT cells in the model group was significantly increased(P0.01), while high-dose YHJF intervention significantly reduced CD160 expression(P0.01). ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160, and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.
3.A bibliometric and visual analysis of the literature published in the journal of Organ Transplantation since its inception
Xi CAO ; Tao HUANG ; Qiwei YANG ; Lin YU ; Xiaowen WANG ; Wenfeng ZHU ; Haoqi CHEN ; Ning FAN ; Genshu WANG
Organ Transplantation 2026;17(1):133-142
Objective To systematically analyze the literature characteristics of Journal of Organ Transplantation since its inception. Methods Using the China National Knowledge Infrastructure (CNKI) academic journal full-text database as the data source, all articles published in the Journal of Organ Transplantation from January 2010 to August 2025 were retrieved. After excluding non-academic papers, a total of 1 568 research papers were included. R language 4.3.0, Bibliometrix package 3.2.1, and Citespace software were used to analyze the number of publications, publishing institutions, authors, keywords and other aspects. Results The number of publications in Journal of Organ Transplantation increased from an average of 82 articles per year in the early years after its inception to 113 articles per year in recent years, a growth of 37.8%. The geographical distribution of publishing institutions covers 32 provinces, cities and autonomous regions nationwide, mainly concentrated in the South China, East China and North China regions, and has now basically covered the central and western regions in recent years. The author collaboration network includes 45 authors distributed across 7 major collaboration clusters, forming a stable multi-level national research system centered on key university-affiliated hospitals. The high-frequency keywords are dominated by "liver transplantation" (425 times) and "kidney transplantation" (396 times). The theme evolution shows a clear three-stage characteristic: initially focusing on clinical technology application, deepening to immune mechanism exploration in the middle stage, and recently (since 2022) focusing on cutting-edge research areas such as xenotransplantation. Conclusions Journal of Organ Transplantation has witnessed the rapid development of China's organ transplantation cause, fully reflecting the research status and trends in China's organ transplantation field, and has provided an important platform for the future development and international cooperation in China's organ transplantation field.
4.Space-time analysis of poor vision among primary and secondary school students in Chengdu from 2021 to 2023
XIE Yuhuan, WANG Zitong, CHEN Xi, YUE Lin, PAN Jie
Chinese Journal of School Health 2025;46(1):29-33
Objective:
To analyze the space time characteristics of poor vision among primary and secondary school students in Chengdu, in order to provide the reference for formulating myopia prevention and control policies for students.
Methods:
The data relating to poor vision among primary and secondary school students in Chengdu from 2021 to 2023 were sourced from the Sichuan Students Physical Health Big Data Center. The districts and counties of Chengdu were divided into three circles, including the main urban area, suburban districts and counties, and suburban districts and counties. The Chi square test was used for inter group comparison, and the Cochran-Armitage test was used to analyze the trend of changes. Global and local Moran s I were used to analyze spatial clustering.
Results:
The detection rates of poor vision among primary and secondary school students in Chengdu from 2021 to 2023 were 62.47%, 61.61% and 60.78%, respectively, showing a decreasing trend ( Z=-32.01, P <0.01). For each year, the higher detection rate of poor vision among students was detected in the higher level of education, and differences were statistically significant ( χ 2=161 549.47, 173 471.87, 233 459.09, P <0.01). The rate of poor vision among primary and secondary school students gradually decreased from the central districts and counties of Chengdu to the surrounding districts and counties for each year, and the differences were statistically significant ( χ 2=299.20, 776.22, 633.16, P <0.01). The spatial autocorrelation analysis showed that the first circle of Chengdu City was mainly characterized by high-high agglomeration ( P <0.01), with the rate of poor vision among primary school students in Wuhou District in 2023 exhibiting a low-high anomaly. The third circle was mainly characterized by low-low aggregation ( P <0.01), while the spatial clusterings of the second circle was not significant ( P >0.05).
Conclusions
The myopia prevention and control work in Chengdu has achieved preliminary results. It should continue to consolidate existing achievements and implement targeted myopia prevention and control measures based on regional characteristics.
5.Characterization of postural stability in elderly patients with idiopathic normal pressure hydrocephalus
Xiaoxiao LIANG ; Jiejiao ZHENG ; Linru DUAN ; Xi CHEN ; Tingyu ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(6):1208-1213
BACKGROUND:Impaired postural control is an important risk factor for falls and secondary damage in patients with idiopathic normal pressure hydrocephalus.Most of the existing studies have analyzed the gait parameters of patients during straight-line walking,but few have analyzed the postural stability characteristics of patients during static and dynamic activities. OBJECTIVE:To analyze the characteristics of postural stability in elderly patients with idiopathic normal pressure hydrocephalus. METHODS:Twenty-two patients clinically diagnosed with idiopathic normal pressure hydrocephalus at the Department of Neurosurgery,Huadong Hospital Affiliated to Fudan University,Shanghai,China,from September 2022 to February 2023 were selected as the patient group,and 18 healthy accompanying family members were selected as the healthy control group.The postural stability characteristics of the subjects were assessed using the Timed Up-and-Go Test,Multi-Directional Reach Test,Berg Balance Scale,and Static Balance Function Test(reaction time,speed of movement,directional control,maximum offset distance,and endpoint travel). RESULTS AND CONCLUSION:The time required to complete the Timed Up-and-Go Test was significantly longer in the patient group than in the healthy control group(P<0.05).The results of the stretching test in the four directions of anterior,posterior,leftand right were significantly lower in the patient group than in the healthy control group(P<0.05).The Berg Balance Scale scores in the patient group were lower than those in the healthy control group(P<0.05).In the Static Balance Function Test,the results of reaction,movement speed,directional control,maximum offset distance and endpoint travel index were smaller in the patient group than the healthy control group(P<0.05).To conclude,patients with idiopathic normal pressure hydrocephalus exhibit overall postural control deficits,and impaired reaction and execution abilities make these patients unable to make timely and accurate motor responses in the face of disturbances from internal or external sources,resulting in postural instability and increasing the risk of falls.
6.Mechanical stability of intertrochanteric fracture of femur with different internal fixation systems
Xi CHEN ; Tao TANG ; Tongbing CHEN ; Qing LI ; Wen ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1783-1788
BACKGROUND:Intertrochanteric fracture of femur has various fracture types and fixation methods,and the mechanical stability of each fixation system is quite different.It is of scientific clinical significance to use finite element analysis method to carry out biomechanical research on various fixation systems. OBJECTIVE:To compare and analyze the mechanical stability of various internal fixations applied to femoral intertrochanteric fracture A031-A2.1 by finite element method. METHODS:Based on the validated finite element model of femur(Intact),the model was cut and made into A031-A2.1 intertrochanteric fracture of femur.Different internal fixation systems were implanted by simulating clinical operation methods,and fixation models of proximal femoral nail antirotation,dynamic hip screw,percutaneous compression plate and proximal femoral locking plate were established respectively.All nodes under the distal femur of the four groups of models were constrained,and compression loads of 700,1 400 and 2 100 N were applied to the femoral head.Von Mises stress distribution and compression stiffness of each group of models were observed through calculation and analysis,and mechanical stability of each group was compared. RESULTS AND CONCLUSION:(1)Through calculation and analysis,after calculating the compression stiffness by comparing the deformation of each model,the compression stiffness of each model under various loads showed the trend:physiological group>proximal femoral nail antirotation group>proximal femoral locking plate group>percutaneous compression plate group>dynamic hip screw group.The compressive stiffness of the complete physiological group model was significantly higher than that of all surgical group models.(2)The stress index was observed.Due to the stress shielding effect,the stress peak value of each fixed group was higher than that of physiological group,and the maximum peak value was concentrated on each internal fixation.Proximal femoral nail antirotation group had the smallest stress peak,while dynamic hip screw group had the highest stress.The stress distribution trend showed physiological group
7.Combination of effective ingredients of traditional Chinese medicine and bone tissue engineering materials for bone repair
Yaokun WU ; Chenglin LIU ; Jiahao FU ; Wei SONG ; Hao CHEN ; Hongzhong XI ; Xin LIU ; Bin DU ; Guangquan SUN
Chinese Journal of Tissue Engineering Research 2025;29(10):2141-2150
BACKGROUND:How to repair bone defect has been a clinical problem for a long time.The effective ingredients of traditional Chinese medicine have good biological activity and therapeutic effect,and the combination of effective ingredients of traditional Chinese medicine and tissue engineering materials has a broad prospect in the field of bone repair.The combination of different effective ingredients of traditional Chinese medicine and scaffolds has similarities in their functional relationships. OBJECTIVE:To collect the cases of the combinations of effective ingredients of traditional Chinese medicine and scaffolds,then analogize tissue engineering scaffolds and effective ingredients of traditional Chinese medicine into two types of traditional Chinese medicine that generate compatibility relationships based on the inspiration of the compatibility of seven emotions and summarize the relationship between the two based on their functional relationships. METHODS:Relevant articles from January 1998 to January 2024 were searched in PubMed and China National Knowledge Infrastructure(CNKI),using English search terms"traditional Chinese medicine,Chinese medicine,traditional Chinese medicine monomers,bone defect,bone repair,bone tissue engineering,tissue engineering,scaffold"and Chinese search terms"traditional Chinese medicine,effective ingredients of traditional Chinese medicine,traditional Chinese medicine monomers,bone tissue engineering,bone tissue engineering scaffold,scaffold,tissue engineering,bone defect,bone repair."A total of 88 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)Both tissue engineering scaffold materials and active ingredients of traditional Chinese medicine have been widely used in the field of bone repair.Although they have obvious advantages in osteogenesis,there are still many shortcomings.Many studies are dedicated to preparing composite materials from the two,hoping to exert a detoxification and synergism through the interaction between the two.(2)Some drugs and materials can promote each other in osteogenesis,antibacterial,and promoting angiogenesis,enhancing their original effects.Inspired by the traditional concept of prescription compatibility,this article summarized it as a"Mutual promotion"relationship and provided examples to support it.(3)Some drugs can enhance the strength of materials,while some materials can achieve sustained release and controlled release effects,increase drug loading and stability,or achieve targeted delivery of drugs loaded on them.The article summarized this unilateral enhancement effect as a"Mutual assistance"relationship.(4)The combination of some traditional Chinese medicine and materials can reduce the toxic side effects of the other party.The article summarizes this detoxification relationship as"Mutual restraint and detoxification."(5)The article provided a new perspective on traditional Chinese medicine composite scaffolds,inspired by the seven emotions compatibility relationship and based on the classification of action relationships.It introduced traditional Chinese medicine concepts into the field of tissue engineering,providing new research ideas for subsequent researchers of composite scaffolds,and providing certain convenience in material selection and matching.
8.Regulatory mechanism of urolithin B in osteoclastic differentiation of bone marrow-derived macrophages
Chinese Journal of Tissue Engineering Research 2025;29(11):2201-2209
BACKGROUND:Urolithin B plays an important role in regulating the body's immune response and has antioxidant,anti-cancer and anti-inflammatory properties.Notably,urolithin B has been reported to have inhibitory effects on osteoclast differentiation of Raw 264.7 cells.However,a more comprehensive understanding of its specific mechanism of action in the context of osteoclast differentiation in bone is worth exploring.Systematic research on the regulatory mechanisms of osteoclast overactivation can help to explore new therapeutic targets,screen and develop safer and more effective therapeutic drugs,and provide new ideas to block the overactivation of osteoclasts. OBJECTIVE:By establishing an in vitro osteoclast differentiation model using bone marrow-derived macrophages,to investigate the effect of urolithin B on nuclear factor-κB receptor-activating factor ligand-mediated osteoclast differentiation and to systematically analyze its mechanism of action. METHODS:(1)The safe working concentration of urolithin B was screened by cell counting kit-8 method.(2)Different concentrations of urolithin B(0,12.5,25,and 50 μmol/L)were used to intervene with the osteoclast differentiation of bone marrow-derived macrophages,and the number of osteoclasts and the size of osteocytes were observed using tartrate-resistant acid phosphatase staining.(3)Different concentrations of urolithin B(0,12.5,25,and 50 μmol/L)were used to intervene with the osteoclast differentiation of bone marrow-derived macrophages,and the relative expression levels of osteoclast-specific genes were detected using real-time fluorescence quantitative PCR.(4)The effect of urolithin B on the P65 and ERK signaling pathways of bone marrow-derived macrophages was observed by western blot.(5)The effect of urolithin B on the key transcription factors nuclear factor of activated T cells 1 and c-Fos in the osteoclastic differentiation of bone marrow-derived macrophages was detected by western blot. RESULTS AND CONCLUSION:50 μmol/L or lower concentration of urolithin B had no effect on the proliferation of bone marrow-derived macrophages but significantly inhibited osteoclastic differentiation of bone marrow-derived macrophages.Urolithin B mainly inhibited osteoclastic differentiation of bone marrow-derived macrophages in pre-medium term.Urolithin B down-regulated the relative expression levels of osteoclast specific genes in bone marrow-derived macrophages.50 μmol/L urolithin B inhibited the phosphorylation levels of P65 and ERK in bone marrow-derived macrophages,which led to the inhibition of osteoclast formation.50 μmol/L urolithin B inhibited the expression of key transcription factors nuclear factor of activated T cells 1 and c-Fos in bone marrow-derived macrophages into osteoclasts.To conclude,urolithin B inhibits bone marrow-derived macrophages from differentiating into osteoclasts by suppressing the expression of downstream osteoclastogenic-related signature genes and downregulating the expression of the important osteoclastogenic transcription factors,nuclear factor of activated T cells 1 and c-Fos,via the P65/ERK signaling axis.
9.Mechanism of HIF-1α in Diabetic Nephropathy and Improvement Effect of Traditional Chinese Medicine: A Review
Jiarun XIE ; Haoyu LIN ; Xi CHEN ; Jia SUN ; Ming WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):287-293
In recent years, diabetic nephropathy (DN) has become an increasingly serious health challenge worldwide, and its morbidity and mortality rates are rapidly increasing. The patients suffering from the disease tend to be younger. DN is not only accompanied by a wide range of renal pathological changes, such as renal hypertrophy, inflammatory cell infiltration, expansion of the tethered membrane stroma, and thickening of the basement membrane but is also the main cause of end-stage renal disease and death in patients with diabetes mellitus. Therefore, it is particularly urgent to explore new strategies for the prevention and treatment of DN. The pathogenesis of DN is intricate and complex, with current research focusing on multifactorial interactions between metabolic and hemodynamic factors, such as hypoxia, inflammatory responses, and fibrotic processes. Notably, hypoxia plays a pivotal role in the initiation and progression of DN. Hypoxia-inducible factor (HIF-1α), as a key regulatory protein commonly found in hypoxic cells, has a profound impact on various physiological and pathological processes, such as cell metabolism, vascular neogenesis, oxidative stress, and apoptosis. With its unique theoretical system and therapeutic approach, traditional Chinese medicine has demonstrated significant advantages in coping with hypoxic diseases and can slow down the progression of DN by regulating the expression level of HIF-1α and its downstream signaling molecules and exerting anti-inflammatory, antioxidant, and antifibrotic effects, which has positive clinical significance for drug development and early prevention and treatment of DN.
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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