1.Relationship between Alzheimer's disease and sarcopenia and body mass index:analysis of GWAS datasets for European populations
Qiwang HE ; Bo CHEN ; Fuchao LIANG ; Zewei KANG ; Yuan ZHOU ; Anxu JI ; Xialin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1036-1046
BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95%confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95%Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95%Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95%Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95%Cl,0.969-0.980;P<0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25%and 32.11%,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.
2.Relationship between Alzheimer's disease and sarcopenia and body mass index:analysis of GWAS datasets for European populations
Qiwang HE ; Bo CHEN ; Fuchao LIANG ; Zewei KANG ; Yuan ZHOU ; Anxu JI ; Xialin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1036-1046
BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95%confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95%Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95%Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95%Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95%Cl,0.969-0.980;P<0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25%and 32.11%,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.
3.Exploring Mechanism of Xiaojinwan-containing Serum in Inhibiting Breast Cancer Cells Based on Wnt/β-catenin Signaling Pathway
Hongdi TANG ; Xiaobo JIN ; Chen GAO ; Hongkai LI ; Zhiming LI ; Lu YAO ; Fengli SONG ; Ning KANG ; Wenwen WANG ; Ying SUN ; Zhibin WANG ; Tong LI ; Yingli ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):13-22
ObjectiveTo investigate the role and underlying mechanism of the Wnt/β-catenin signaling pathway in the process of Xiaojinwan (XJW)-containing serum interfering with endothelial-mesenchymal transition (EMT) in human breast cancer MDA-MB-231 cells. MethodsXJW-containing serum was prepared by intragastric administration of XJW (4 g·kg-1) to SD rats. MDA-MB-231 cells were cultured in vitro. β-Catenin overexpression and knockdown plasmids were constructed and transfected into MDA-MB-231 cells. The optimal XJW-containing serum (4 g·kg-1) according to previous studies was used for β-catenin intervention and overexpression experiments. The groups for intervention/overexpression experiments included intervention/overexpression blank group, β-catenin intervention/overexpression group, intervention/overexpression blank + XJW group, and β-catenin intervention/overexpression + XJW group. Cell morphology was observed under a microscope. Flow cytometry was used to detect and record apoptosis rates. Western blot was performed to measure apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and active-Caspase-3] and EMT-related proteins (E-cadherin, N-cadherin, and vimentin). Real-time polymerase chain reaction (Real-time PCR) was used to detect β-catenin mRNA expression levels in different groups. ResultsIntervention experiment results showed that compared with the intervention blank group, the β-catenin intervention group and the intervention blank + XJW group showed increased apoptosis rates (P<0.05, P<0.01), elevated protein levels of Bax, active Caspase-3, and E-cadherin (P<0.05, P<0.01), and decreased protein levels of Bcl-2 and Vimentin (P<0.05, P<0.01). β-catenin mRNA expression was reduced in the β-catenin intervention group (P<0.05, 0.63 ± 0.15) and the intervention blank + XJW group (P<0.05, 0.79 ± 0.33). Compared with the β-catenin intervention group, the β-catenin intervention + XJW group exhibited an increased apoptosis rate (P<0.01), elevated Bax and active Caspase-3 protein levels (P<0.05, P<0.01), and decreased Bcl-2, N-cadherin, and Vimentin protein levels (P<0.05). β-catenin mRNA expression was further reduced in the β-catenin intervention + XJW group (P<0.01, 0.22 ± 0.08). Compared with the intervention blank + XJW group, the β-catenin intervention + XJW group showed an increased apoptosis rate (P<0.01), elevated Bax, active Caspase-3, and E-cadherin protein levels (P<0.05, P<0.01), and decreased Bcl-2, N-cadherin, and vimentin protein levels (P<0.05, P<0.01). β-catenin mRNA expression was also reduced (P<0.05). Overexpression experiment results showed that compared with the overexpression blank group, the β-catenin overexpression group exhibited a reduced apoptosis rate (P<0.01), while the overexpression blank + XJW group showed an increased apoptosis rate (P<0.05). In the β-catenin overexpression and β-catenin overexpression + XJW groups, Bax and E-cadherin protein levels decreased (P<0.05, P<0.01), while Bcl-2, N-cadherin, and vimentin levels increased (P<0.05). In the overexpression blank + XJW group, Bax and E-cadherin levels increased (P<0.05, P<0.01), while Bcl-2, N-cadherin, and vimentin levels decreased (P<0.05, P<0.01). β-catenin mRNA expression increased in the β-catenin overexpression group (P<0.01, 7.26 ± 1.03) but decreased in the overexpression blank + XJW group (P<0.05, 0.73 ± 0.14). Compared with the β-catenin overexpression group, the β-catenin overexpression + XJW group showed an increased apoptosis rate (P<0.01), elevated Bax and E-cadherin levels (P<0.05), and decreased N-cadherin and vimentin levels (P<0.05). β-catenin mRNA expression was reduced (P<0.05, 4.65 ± 1.02). Compared with the overexpression blank + XJW group, the β-catenin overexpression + XJW group exhibited a reduced apoptosis rate (P<0.01), decreased Bax and E-cadherin levels (P<0.01), and increased Bcl-2, N-cadherin, and Vimentin levels (P<0.05). β-catenin mRNA expression increased (P<0.01). ConclusionXJW-containing serum inhibits breast cancer cell proliferation by suppressing EMT, which is associated with the regulation of the Wnt/β-catenin pathway.
4.4-Octyl itaconate inhibits synovitis in the mouse model of post-traumatic osteoarthritis and alleviates pain.
Yu-Zhen TANG ; Wan CHEN ; Bao-Yun XU ; Gang HE ; Xiu-Cheng FAN ; Kang-Lai TANG
Chinese Journal of Traumatology 2025;28(1):50-61
PURPOSE:
To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis (PTOA) treated with 4-octyl itaconate (4-OI) and evaluate the therapeutic effects of 4-OI.
METHODS:
In the phenotypic validation experiment, the mice were randomly divided into 3 groups: wild-type (WT) group, sham group, and destabilization of the medial meniscus (DMM) group. Through MRI, micro-CT, and histological analysis, it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis. At 12 weeks post-DMM surgery, synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis. In the 4-OI treatment experiment, mice were randomly divided into the sham group, DMM group, DMM + 4-OI (50 mg/kg) group, and DMM + 4-OI (100 mg/kg) group. Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery. After 12 weeks of surgery, the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI, micro-CT, histological analysis, and quantitative real-time polymerase chain reaction. Finally, we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation. Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test. Difference was considered statistically significant at p < 0.05.
RESULTS:
The DMM surgery effectively induced a PTOA mouse model, which displayed significant symptoms of synovitis. These symptoms included a notable increase in both the number of calcified tissues and osteophytes (p < 0.001), an enlargement of the calcified meniscus and synovial tissue volume (p < 0.001), and thickening of the synovial lining layer attributable to M1 macrophage accumulation (p = 0.035). Additionally, we observed elevated histological scores for synovitis (p < 0.001). Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice (p < 0.001) and reduced fibrosis in the synovial stroma (p = 0.004). Furthermore, it reduced the histological scores of knee synovitis in PTOA mice (p = 0.006) and improved the inflammatory microenvironment associated with synovitis. Consequently, this treatment alleviated pain in PTOA mice (p < 0.001) and reduced spontaneous activity (p = 0.003). Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells. Specifically, compared to the lipopolysaccharide stimulation group, 4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation (IL-1: p < 0.001, IL-6: p < 0.001), key effector molecules (IL-17A: p < 0.001, IL-17F: p = 0.004), and downstream effector molecules in the IL-17 signaling pathway (CCL2: p < 0.001, MMP13: p < 0.001).
CONCLUSION
4-OI is effective in inhibiting synovitis in PTOA, thereby alleviating the associated painful symptoms.
Animals
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Synovitis/etiology*
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Mice
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Osteoarthritis/etiology*
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Disease Models, Animal
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Male
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Succinates/pharmacology*
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Mice, Inbred C57BL
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X-Ray Microtomography
5.Comparative analysis of the safety and efficacy of fenestrated pedicle screw with cement and conventional pedicle screw with cement in the treatment of osteoporotic vertebral fractures: A meta-analysis.
Li CAO ; Hong-Jie XU ; Yi-Kang YU ; Huan-Huan TANG ; Bo-Hao FANG ; Ke CHEN
Chinese Journal of Traumatology 2025;28(2):101-112
PURPOSE:
Bone cement-reinforced fenestrated pedicle screws (FPSs) have been widely used in the internal fixation and repair of the spine with osteoporosis in recent years and show significant improvement in fixation strength and stability. However, compared with conventional reinforcement methods, the advantages of bone cement-reinforced FPSs remain undetermined. This article compares the effects of fenestrated and conventional pedicle screws (CPSs) combined with bone cement in the treatment of osteoporosis.
METHODS:
A clinical control study of FPSs and CPSs combined with bone cement reinforcement in osteoporotic vertebral internal fixation was performed using the database PubMed, Embase, Cochrane Library, CNKI, the Wanfang, and the China Biomedical Literature Service System. Two evaluators screened the relevant literature in strict accordance with the inclusion criteria (diagnosis of participants, type of clinical study, treatment with FPS and CPS, and outcome indicators) and exclusion criteria (duplicate literature and missing or incorrect data) and independently conducted data extraction and quality evaluation. Clinical control studies of direct comparison between FPS and CPS combined with bone cement reinforcement in patients who were definitively diagnosed with thoracolumbar fractures or spinal degenerative diseases were included. Quality evaluation was conducted using the Cochrane risk bias evaluation tool for randomized controlled studies and using the Newcastle-Ottawa scale for retrospective case-control studies. RevMan software (version 5.3) was used for the meta-analysis to compare the clinical efficacy, radiological results, and related complications of the 2 methods.
RESULTS:
A total of 13 articles were included, including 7 randomized controlled studies and 6 retrospective case-control studies. There were 909 patients in these studies, 451 in the FPS and polymethyl methacrylate (FPS & PMMA) group and 458 in the CPS and polymethyl methacrylate (CPS & PMMA) group. The results of the meta-analysis showed that there was no significant difference between the 2 groups in operation time, hospital stay, visual analogue score, Japanese orthopaedic association score, Oswestry disability index score, Cobb angle, vertebral body deformation index and fusion rate (p > 0.05). The mean difference of intraoperative bleeding volume was -10.45, (95% confidence intervals (CI) (-16.92, -3.98), p = 0.002), the mean difference of loss height of the anterior edge of the vertebral body after surgery was -0.69 (95% CI (-0.93, -0.44), p < 0.001), and the relative risk (RR) of overall complication rate was 0.43 (95% CI (0.27, 0.68), p < 0.001), including the RR of bone cement leakage rate was 0.57 (95% CI (0.39, 0.85), p = 0.005). The screw loosening rate (RR = 0.26, 95% CI (0.13, 0.54), p < 0.001) of the FPS group was significantly lower than that of the CPS group.
CONCLUSION
The existing clinical evidence shows that compared with the CPS combined with bone cement, the use of FPS repair in the internal fixation of an osteoporotic vertebral body can reduce the amount of intraoperative bleeding, be more conducive to maintaining the height of the vertebral body, and significantly reduce the incidence of postoperative complications such as bone cement leakage and screw loosening.
Humans
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Pedicle Screws
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Bone Cements
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Spinal Fractures/surgery*
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Osteoporotic Fractures/surgery*
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Fracture Fixation, Internal/instrumentation*
6.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
7.Specific extraction and analysis of synthesized proteins from mesenchymal stem cells transplanted into the ischemic heart
Wan-Er LU ; Ying DAI ; Mu-Han TANG ; Kang WEI ; Shu-Jia CHEN ; Huai HUANG ; Jing LIN ; Hao-Rong PENG ; Li-Xuan ZHOU ; Dun-Zheng HAN
Medical Journal of Chinese People's Liberation Army 2025;50(8):991-998
Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P<0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P<0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P<0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P<0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P<0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.
8.Quercetin ameliorates myocardial injury in diabetic rats by regulating L-type calcium channels.
Hongyan SUN ; Guoqing LU ; Chengwen FU ; Mengwen XU ; Xiaoyi ZHU ; Guoquan XING ; Leqiang LIU ; Yufei KE ; Lemei CUI ; Ruiyang CHEN ; Lei WANG ; Pinfang KANG ; Bi TANG
Journal of Southern Medical University 2025;45(3):531-541
OBJECTIVES:
To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats.
METHODS:
Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique.
RESULTS:
The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin.
CONCLUSIONS
Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals
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Quercetin/pharmacology*
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Calcium Channels, L-Type/metabolism*
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Diabetes Mellitus, Experimental/metabolism*
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Rats, Sprague-Dawley
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Rats
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Myocytes, Cardiac/drug effects*
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Myocardium/pathology*
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Male
9.Genome-wide investigation of transcription factor footprints and dynamics using cFOOT-seq.
Heng WANG ; Ang WU ; Meng-Chen YANG ; Di ZHOU ; Xiyang CHEN ; Zhifei SHI ; Yiqun ZHANG ; Yu-Xin LIU ; Kai CHEN ; Xiaosong WANG ; Xiao-Fang CHENG ; Baodan HE ; Yutao FU ; Lan KANG ; Yujun HOU ; Kun CHEN ; Shan BIAN ; Juan TANG ; Jianhuang XUE ; Chenfei WANG ; Xiaoyu LIU ; Jiejun SHI ; Shaorong GAO ; Jia-Min ZHANG
Protein & Cell 2025;16(11):932-952
Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics*
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Humans
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Chromatin/genetics*
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Animals
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Binding Sites
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Mice
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DNA Footprinting/methods*
10.Safety and effectiveness of lecanemab in Chinese patients with early Alzheimer's disease: Evidence from a multidimensional real-world study.
Wenyan KANG ; Chao GAO ; Xiaoyan LI ; Xiaoxue WANG ; Huizhu ZHONG ; Qiao WEI ; Yonghua TANG ; Peijian HUANG ; Ruinan SHEN ; Lingyun CHEN ; Jing ZHANG ; Rong FANG ; Wei WEI ; Fengjuan ZHANG ; Gaiyan ZHOU ; Weihong YUAN ; Xi CHEN ; Zhao YANG ; Ying WU ; Wenli XU ; Shuo ZHU ; Liwen ZHANG ; Naying HE ; Weihuan FANG ; Miao ZHANG ; Yu ZHANG ; Huijun JU ; Yaya BAI ; Jun LIU
Chinese Medical Journal 2025;138(22):2907-2916
INTRODUCTION:
Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD.
METHODS:
In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging.
RESULTS:
A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline.
CONCLUSIONS:
Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies.
REGISTRATION
ClinicalTrials.gov , NCT07034222.
Humans
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Alzheimer Disease/drug therapy*
;
Male
;
Female
;
Aged
;
Middle Aged
;
Cognitive Dysfunction/drug therapy*
;
Aged, 80 and over
;
Amyloid beta-Peptides/metabolism*
;
Biomarkers
;
East Asian People

Result Analysis
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