1.Protective effects of p53/GLUT4 regulation on cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation
Aheniyazi ALIYANMU ; Fen LIU ; Haoyan JIANG ; Yunze WANG ; Rong ZHANG ; Yajing QIU ; Runxuan HU ; Yining YANG
International Journal of Biomedical Engineering 2025;48(2):124-136
Objective:To investigate the protective effects of p53/glucose transporter 4 (GLUT4) regulation on cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.Methods:Human myocardial AC16 cells were treated with 33 mmol/L glucose and a hypoxic chamber to establish an in vitro model of high glucose combined with hypoxia/reoxygenation. Based on the glucose concentration in the medium and hypoxia/reoxygenation conditions, AC16 cells were divided into control group, high glucose group, hypoxia/reoxygenation group and high glucose combined with hypoxia/reoxygenation group. On the basis of high glucose combined with hypoxia/reoxygenation group, cells were transfected with empty vector, p53 small interfering RNA (siRNA), and co-transfected with p53 and GLUT4 siRNA to establish negative control group, sip53 transfection group, and sip53+siGLUT4 transfection group, respectively. Western blotting was used to detect the levels of hypoxia-inducible factor-1α (HIF-1α), p53, GLUT4, dynamin-related protein 1 (Drp1), mitofusin 2 (Mfn2), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartic acid specific protease-3 (Caspase-3). The levels of reactive oxygen species were detected using the 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Mitochondria were labeled with the Mito-Tracker Deep Red FM fluorescent probe to assess mitochondrial morphology and their related parameters. Mitochondrial membrance potential was meausred using the JC-1 detection kit. Adenosine triphosphate (ATP) content was determined using an ATP assay kit. Glucose uptake ability was evaluated by measuring the fluorescence intensity of 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy- D-glucose (2-NBDG) using a multifunctional microplate reader. Apoptosis was assessed by TUNEL assay. Results:The relative expression of HIF-1α protein in the high glucose combined with hypoxia/reoxygenation group was 1.189±0.185, higher than that in the control group (0.086±0.071) ( P<0.05). The relative expression of p53 protein in the high glucose combined with hypoxia/reoxygenation group was 1.248±0.194, higher than those in the control group (0.730±0.184), high glucose group (0.932±0.161) and hypoxia/reoxygenation group (1.109±0.151) (all P<0.05). The relative expression of GLUT4 protein in the high glucose combined with hypoxia/reoxygenation group was 0.407±0.140, lower than those in the control group (1.061±0.060) and hypoxia/reoxygenation group (0.781±0.092) (both P<0.05). The fluorescence intensity of reactive oxygen species in the high glucose combined with hypoxia/reoxygenation group was 38.31±1.66, higher than that in the control group (11.59±1.02) ( P<0.05). The number of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (62.00±15.26), lower than those in the control group (136.20±23.55) and high glucose group (96.55±13.72) (both P<0.05). The average mitochondrial area in the high glucose combined with hypoxia/reoxygenation group was (7.02±1.38) μm 2, lower than those in the control group [(13.74±0.67) μm 2], high glucose group [(9.27±1.99) μm 2] and hypoxia/reoxygenation group [(9.64±2.36) μm 2] (all P<0.05). The average perimeter of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (9.10±1.14) μm, lower than those in the control group [(13.35±0.69) μm] and the hypoxia/reoxygenation group [(10.83±1.58) μm] (all P<0.05). The number of mitochondrial branches was 53.73±9.49, lower than those in the control group (147.10±25.99), high glucose group (97.08±13.65) and hypoxia/reoxygenation group (104.80±24.92) (all P<0.05). The average branch length of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (1.45±0.26) μm, lower than that in the control group [(2.29±0.52) μm] ( P<0.05). The red-green fluorescence intensity ratio in the high glucose combined with hypoxia/reoxygenation group was 0.580±0.133, lower than those in the control group (2.379±0.242), high glucose group (1.200±0.112) and hypoxia/reoxygenation group (0.883±0.076) (all P<0.05). The ATP content of the high glucose combined with hypoxia/ reoxygenation group was (0.025±0.003) μmol/10 5 cells, lower than those of the control group [(0.137±0.012) μmol/10 5 cells], high glucose group [(0.078±0.003) μmol/10 5 cells] and hypoxia/reoxygenation group [(0.073±0.010) μmol/10 5 cells] (all P<0.05). The fluorescence intensity of 2-NBDG in the high glucose combined with hypoxia/reoxygenation group was 257 315±7 951, lower than those in the control group (339 597±10 165), high glucose group (317 293±8 876) and hypoxia/reoxygenation group (314 611±12 228) (all P<0.05). The relative expression of Drp1 protein in high glucose combined with hypoxia/reoxygenation group was 1.203±0.090, higher than those in the control group (0.705±0.170), high glucose group (0.910±0.106) and hypoxia/reoxygenation group (1.002±0.112) (all P<0.05). The relative expression of Mfn2 protein in the high glucose combined with hypoxia/reoxygenation group was 0.706±0.285, lower than those in the control group (1.988±0.139), high glucose group (1.305±0.076) and hypoxia/reoxygenation group (1.131±0.236) (all P<0.05). The relative expression levels of Bax/Bcl-2 and Caspase-3 proteins in the high glucose combined with hypoxia/reoxygenation group were 2.318±0.216 and 1.076±0.076, respectively, higher than those in the control group (0.281±0.046 and 0.442±0.084), high glucose group (0.673±0.043 and 0.662±0.159) and hypoxia/reoxygenation group (0.807±0.293 and 0.835±0.058), respectively (all P<0.05). The TUNEL fluorescence intensity of the high glucose combined with hypoxia/reoxygenation group was 70.55±7.22, higher than those of the control group (14.10±5.93), high glucose group (36.59±2.56) and hypoxia/reoxygenation group (39.04±6.016) (all P<0.05). The relative expression levels of p53 protein in the sip53 transfection group and sip53+siGLUT4 transfection group were 0.322±0.147 and 0.391±0.149, respectively, lower than that in the high glucose combined with negative control group (1.002±0.035) (both P<0.05). The relative expression of GLUT4 protein in the sip53 transfection group was 1.871±0.123, higher than that in the negative control group (1.281±0.232) ( P<0.05). The relative expression of GLUT4 protein in the sip53+siGLUT4 transfection group (0.951±0.193) was lower than that in the sip53 transfection group ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53 transfection group (27.73±0.74) was lower than that in the negative control group (38.83±0.83) ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53+siGLUT4 transfection group (43.12±5.08) was higher than that in the sip53 transfection group ( P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53 transfection group were (92.27±10.10), (9.25±0.42) μm 2, (10.86±0.58) μm, (83.27±13.57), and (1.81±0.21) μm, respectively. They were higher than (52.36±16.87), (7.44±1.49) μm 2, (9.22±1.11) μm, (52.36±16.87), and (1.22±0.26) μm in the negative control group (all P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53+siGLUT4 transfection group were (53.73±9.49), (6.89±0.61) μm 2, (8.88±0.47) μm, (53.73±9.49), and (1.22±0.17) μm, respectively, lower than those in the sip53 transfection group (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53 transfection group were 1.27±0.23, (0.048±0.021) μmol/10 5 cells, 275 923±10 447 and 2.608±0.581, respectively, higher than those in the negative control group [0.53±0.21, (0.020±0.007) μmol/10 5 cells, 254 875±8 078, and 0.687±0.146, respectively] (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53+siGLUT4 transfection group were 0.40±0.08, (0.011±0.012) μmol/10 5 cells, 199 511±6 855, and 0.649±0.070, respectively, lower than those in the sip53 transfection group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53 transfection group were 0.759±0.063, 0.446±0.161, 1.048±0.300, and 48.93±1.48 respectively, lower than those (1.065±0.149, 1.197±0.133, 1.847±0.201, and 67.61±9.99) in the negative control group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53+siGLUT4 transfection group were 0.958±0.166, 2.660±0.135, 1.587±0.220, and 63.39±12.84, respectively, higher than those in the sip53 transfection group (all P<0.05). Conclusions:Under the condition of high glucose combined with hypoxia/reoxygenation, p53 induces cardiomyocyte injury by down-regulating GLUT4. Inhibition of p53 can increase the expression of GLUT4, thereby reducing cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.
2.Determination of malononitrile in workplace air by solvent desorption- gas chromatography
Jiaheng HE ; Guangkeng HU ; Jiawen HU ; Jing YUAN ; Jinging QIU ; Weifeng RONG ; Banghua WU
China Occupational Medicine 2025;52(6):677-681
Objective To develop a solvent desorption-gas chromatography method for quantifying malononitrile in workplace air. Methods Malononitrile in workplace air was collected using a silica gel tube and desorbed with methanol. Separation was performed using DB-FFAP capillary column, and detection was performed by hydrogen flame ionization detector. Results The linear ranges of malononitrile were 4.00-600.00 mg/L, with the correlation coefficient of 0.999 92. The detection limit was 0.54
3.Traditional Chinese medicine understanding and treatment strategies for hypertension com plicated by chronic low back pain from perspective of kidney deficiency syndrome.
Zheng-Rong LUO ; Yin-Qiu GAO ; Xing-Jiang XIONG ; Pin LYU ; Xiao-Chen YANG
China Journal of Chinese Materia Medica 2025;50(4):1121-1131
In China, the number of chronic pain patients has exceeded 300 million, making chronic pain the third major health problem after tumors and cardiovascular diseases. Particularly concerning is the gradual emergence of hypertension and chronic low back pain as public health problems that threaten public health and increase the global economic burden. Modern research shows that the incidence of coexisting hypertension is higher among patients with chronic low back pain. Additionally, evidence indicates that the use of NSAIDs for pain relief can have adverse effects on blood pressure, and some antihypertensive medications may trigger symptoms of low back pain. Thus, addressing chronic pain in hypertensive patients while stabilizing blood pressure is one of the important research questions in the modern treatment of hypertension among middle-aged and elderly individuals. From ancient to modern traditional Chinese medicine(TCM) theory, kidney deficiency has been regarded as the core pathogenesis of low back pain. Recent clinical practices and literature indicate that kidney deficiency plays a crucial role in the modern pathogenesis of hypertension. Both hypertension and chronic low back pain are closely associated with kidney deficiency in TCM theory, revealing a potential mechanism linking the two conditions. Combining the theories of " kidney-essence-marrow" and " nourishing water to moisten wood", a therapeutic strategy centered on tobifying kidney was proposed, including selecting single drugs with kidney-tonifying effects as well as compound formulations and elaborating modern research evidence. The aim is to achieve stable blood pressure control in hypertension patients with chronic low back pain while providing a new treatment perspective for chronic low back pain. This article systematically elaborates on the understanding of hypertension combined with chronic low back pain from both TCM and modern medicine, as well as the therapeutic strategy involving kidney-tonifying drugs, to offer useful references for clinical practice.
Humans
;
Hypertension/complications*
;
Low Back Pain/complications*
;
Drugs, Chinese Herbal/therapeutic use*
;
Kidney/drug effects*
;
Medicine, Chinese Traditional
;
Chronic Pain/drug therapy*
4.Chemical constituents of Sophorae Flavescentis Radix and its residue based on UPLC-Q-TOF-MS.
Qian-Wen LIU ; Rong-Qing ZHU ; Qian-Nan HU ; Xiang LI ; Guang YANG ; Zi-Dong QIU ; Zhi-Lai ZHAN ; Tie-Gui NAN ; Mei-Lan CHEN ; Li-Ping KANG
China Journal of Chinese Materia Medica 2025;50(3):708-718
Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry*
;
Chromatography, High Pressure Liquid/methods*
;
Mass Spectrometry/methods*
;
Sophora/chemistry*
;
Flavonoids/chemistry*
;
Alkaloids/chemistry*
5.Mechanism of action of ginsenoside Rg_2 on diabetic retinopathy and angiogenesis based on YAP/TLRs pathway.
Zhuo-Rong LIU ; Yong-Li SONG ; Shang-Qiu NING ; Yue-Ying YUAN ; Yu-Ting ZHANG ; Gai-Mei HAO ; Jing HAN
China Journal of Chinese Materia Medica 2025;50(6):1659-1669
Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals
;
Ginsenosides/pharmacology*
;
Diabetic Retinopathy/physiopathology*
;
Mice
;
YAP-Signaling Proteins
;
Humans
;
Male
;
Signal Transduction/drug effects*
;
Cell Movement/drug effects*
;
Adaptor Proteins, Signal Transducing/genetics*
;
Mice, Inbred C57BL
;
Neovascularization, Pathologic/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
Panax notoginseng/chemistry*
;
Endothelial Cells/metabolism*
;
Transcription Factors/genetics*
;
Angiogenesis
6.Short- to medium-term safety and efficacy of the implantable Corheart 6 left ventricular assist system in patients with end-stage heart failure
Zhibing QIU ; Xiaochun SONG ; Liangpeng LI ; Hongwei SHI ; Liqiong XIAO ; Yunzhang WU ; Xiaosong RONG ; Jidan FAN ; Liang WEI ; Xin CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):639-645
Objective To investigate the efficacy and safety of the Corheart 6 left ventricular assist system in patients with end-stage heart failure. Methods A retrospective study was conducted on patients with end-stage heart failure who were treated with Corheart 6 left ventricular assist system from March 2022 to June 2024 in 4 hospitals in Jiangsu Province. The efficacy of the device was evaluated by comparing changes in clinical indicators at preoperative, discharge, 3-month postoperative, and 6-month postoperative timepoints, including the New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic diameter (LVEDD). The safety of the device was assessed by analyzing the intraoperative position and orientation of the blood pump inlet cannula, as well as the incidence of adverse events. Results In this study, 39 patients were collected, including 34 males and 5 females with a mean age of (56.4±12.5) years, ranging from 20 to 75 years. There was no operative death. There was no death in postoperative 3 months with a survival rate of 100.0%. There were 3 deaths in 6 months postoperatively, with a survival rate of 92.3%. All patients had a preoperative NYHA cardiac function classification of class Ⅳ. The NYHA cardiac function class of the patients improved (P<0.05) at discharge, 3 and 6 months after surgery when compared to the preoperative period. LVEF was significantly higher at 3 months after surgery than that during the preoperative period (P<0.05). LVEDD was significantly smaller at discharge, 3 and 6 months after surgery than that during the preoperative period (P<0.05). The safety evaluation's findings demonstrated that all 39 patients' intraoperative blood pump inlet tubes were oriented correctly, the artificial blood vessel suture sites were appropriate, there were no instances of device malfunction or pump thrombosis, or instances of bleeding or hemolysis, and the rate of the remaining adverse events was low. Conclusion With a low rate of adverse events and an excellent safety profile, the Corheart 6 left ventricular assist system can efficiently enhance cardiac function in patients with end-stage heart failure. It also has considerable clinical uses.
7.Novel araucarene diterpenes from Agathis dammara exert hypoglycemic activity by promoting pancreatic β cell regeneration and glucose uptake.
Zhewei YU ; Yi ZHANG ; Wenhui WANG ; XinYi WU ; Shunzhi LIU ; Yanlin BIN ; Hongsheng LI ; Bangping CAI ; Zheng WANG ; Meijuan FANG ; Rong QI ; Mingyu LI ; Yingkun QIU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(4):492-503
In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish
;
Animals
;
Diterpenes/isolation & purification*
;
Insulin-Secreting Cells/cytology*
;
Glucose/metabolism*
;
Hypoglycemic Agents/isolation & purification*
;
Molecular Structure
;
Structure-Activity Relationship
;
Plant Extracts/pharmacology*
;
Regeneration/drug effects*
8.Inflammatory Bowel Disease and Dementia: Evidence Triangulation from a Meta-Analysis of Observational Studies and Mendelian Randomization Study.
Di LIU ; Mei Ling CAO ; Shan Shan WU ; Bing Li LI ; Yi Wen JIANG ; Teng Fei LIN ; Fu Xiao LI ; Wei Jie CAO ; Jin Qiu YUAN ; Feng SHA ; Zhi Rong YANG ; Jin Ling TANG
Biomedical and Environmental Sciences 2025;38(1):56-66
OBJECTIVE:
Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal.
METHODS:
We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence.
RESULTS:
Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I 2 = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I 2 = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.
CONCLUSION
Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans
;
Mendelian Randomization Analysis
;
Inflammatory Bowel Diseases/complications*
;
Dementia/etiology*
;
Observational Studies as Topic
;
Genome-Wide Association Study
9.Construction of a Disulfidptosis-Related Prediction Model for Acute Myocardial Infarction Based on Transcriptome Data.
Qiu-Rong TANG ; Yang FENG ; Yao ZHAO ; Yun-Fei BIAN
Acta Academiae Medicinae Sinicae 2025;47(3):354-365
Objective To identify disulfidptosis-related gene(DRG)in acute myocardial infarction(AMI)by bioinformatics,analyze the molecular pattern of DRGs in AMI,and construct a DRGs-related prediction model.Methods AMI-related datasets were downloaded from the Gene Expression Omnibus database,and DRGs with differential expression were screened in AMI.CIBERSORT method was used to analyze the immune infiltration.Based on the differentially expressed DRGs,the AMI patients were classified into distinct subtypes via consensus clustering,followed by immune infiltration analysis,differential expression analysis,gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis,and gene set variation analysis.Weighted gene co-expression network analysis(WGCNA)was then performed to construct subtype-associated modules and identify hub genes.Finally,least absolute shrinkage and selection operator,random forest,and support vector machine-recursive feature elimination were used to screen feature genes to construct a DRGs-related prediction model.The model's diagnostic efficacy was evaluated by nomogram and receiver operating characteristic(ROC)curve analysis,followed by external validation.Results Nine differentially expressed DRGs were identified between AMI patients and controls.Based on the expression levels of these nine DRGs,AMI patients were divided into two DRGs subtypes,C1 and C2.Increased infiltration of monocytes,M0 macrophages,and neutrophils was observed in AMI patients and C1 subtype(all P<0.05),indicating a close correlation between DRGs and immune cells.There were 257 differentially expressed genes between the C1 and C2 subtypes,which were related to biological processes such as myeloid leukocyte activation and positive regulation of cytokines.Fcγ receptor-mediated phagocytosis and NOD-like receptor signaling pathway activity were enhanced in C1 subtype.WGCNA analysis suggested that the brown module exhibited the strongest correlation with DRG subtypes(r=0.67),from which 23 differentially expressed genes were identified.The feature genes screened by three machine learning methods were interpolated to obtain a DRGs-related prediction model consisting of three genes(AQP9,F5 and PYGL).Nomogram and ROC curves(AUCtrain=0.891,AUCtest=0.840)showed good diagnostic efficacy.Conclusions DRGs were closely related to the occurrence and progression of AMI.The DRGs-related prediction model consisting of AQP9,F5 and PYGL may provide targets for the diagnosis and personalized treatment of AMI.
Humans
;
Myocardial Infarction/diagnosis*
;
Transcriptome
;
Computational Biology
;
Gene Expression Profiling
;
ROC Curve
;
Gene Regulatory Networks
;
Nomograms
;
Disulfidptosis
10.Pien Tze Huang Attenuates Cell Proliferation and Stemness Promoted by miR-483-5p in Hepatocellular Carcinoma Cells.
Li-Hui WEI ; Xi CHEN ; A-Ling SHEN ; Yi FANG ; Qiu-Rong XIE ; Zhi GUO ; Thomas J SFERRA ; You-Qin CHEN ; Jun PENG
Chinese journal of integrative medicine 2025;31(9):782-791
OBJECTIVE:
To investigate the effect of miR-483-5p on hepatocellular carcinoma (HCC) cells proliferation and stemness, as well as the attenuating effect of Pien Tze Huang (PZH).
METHODS:
Differentially expressed miRNA between HepG2 cells and hepatic cancer stem-like cells (HCSCs) were identified by a miRNA microarray assay. miR-483-5p mimics were transfected into HepG2 cells to explore the effects of miR-483-5p on cell proliferation and stemness. HepG2 cells and HCSCs were treated with PZH (0, 0.25, 0.50 and 0.75 mg/mL) to explore the effects of PZH on the proliferation and stemness, both in non-induced state and the state induced by miR-483-5p mimics.
RESULTS:
miR-483-5p was significantly up-regulated in HCSCs and its overexpression increased cell proliferation and stemness in HepG2 cells (P<0.05). PZH not only significantly inhibited proliferation in HepG2 cells, but also significantly suppressed the cell proliferation and self-renewal of HCSCs (P<0.05). The effects of miR-483-5p mimics on proliferation and stemness of HepG2 cells were partially abolished by PZH.
CONCLUSIONS
miR-483-5p promotes proliferation and enhances stemness of HepG2 cells, which were attenuated by PZH, demonstrating that miR-483-5p is a potential molecular target for the treatment of HCC and provide experimental evidence to support clinical use of PZH for patients with HCC.
Humans
;
MicroRNAs/metabolism*
;
Cell Proliferation/drug effects*
;
Liver Neoplasms/drug therapy*
;
Carcinoma, Hepatocellular/drug therapy*
;
Hep G2 Cells
;
Neoplastic Stem Cells/metabolism*
;
Drugs, Chinese Herbal/therapeutic use*
;
Gene Expression Regulation, Neoplastic/drug effects*

Result Analysis
Print
Save
E-mail