1.Advancement of functional peptides: Promising candidates for antituberculosis therapeutics
Bojie LIN ; Siqi LIN ; Jiayi YANG ; Xuanyu YANG ; Shuhui WANG ; Yuting LIU ; Qianqian ZHANG ; Junfa XU ; Jiang PI ; Fen YANG
Science of Traditional Chinese Medicine 2026;4(1):24-32
Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, is primarily airborne and remains a global health problem, especially in resource-limited countries and regions. The emergence of drug resistance in M. tuberculosis has rendered the existing means ineffective in the treatment of TB. Therefore, research in new therapeutic directions has become imperative. In this review, we outline functional peptides in terms of the mechanisms of action, anti-TB attempts, advantages and disadvantages, and latest advances, aiming to analyze the research progress in anti-TB peptides. Furthermore, we investigate the potential applications of bioactive compounds found in traditional Chinese Medicine within the context of peptides.
2.Logistics regression analysis of plastic bronchitis in children with mycoplasma pneumoniae infection
Fen OU ; Taoyi YANG ; Guanglei CHEN ; Hongxia LI ; Pingping LI
Journal of Public Health and Preventive Medicine 2025;36(1):160-163
Objective To analyze the influencing factors of plastic bronchitis in children with Mycoplasma pneumoniae infection and put forward targeted prevention suggestions. Methods The clinical data of children with Mycoplasma pneumoniae infection who were admitted to Chengdu Third People's Hospital from September 2022 to February 2024 were retrospectively analyzed . According to whether plastic bronchitis occurred, they were divided into plastic group (n=118) and non-plastic group (n=184), and the differences between the two groups were compared and analyzed. Univariate and multivariate logistics regression analysis equations were used to analyze the independent influencing factors of plastic bronchitis in children with mycoplasma pneumoniae infection. Results Among the 302 children with Mycoplasma pneumoniae infection , 118 cases were diagnosed with plastic bronchitis. Analysis showed that the children’s age, duration of fever, hospital stay, pleural effusion rate, number of bronchoscopic lavage, allergy history, endoscopic mucosal erosion rate, WBC, NE%, LY%, CRP, LDH, PCT and D-D were the single factors influencing the occurrence of plastic bronchitis in children with mycoplasma pneumoniae infection. Binary logistics regression analysis revealed that age (OR=2.137, P=0.033, 95% CI: 1.132-16.603), allergy history (OR=3.028, P=0.014, 95% CI: 1.261-864), NE% (OR=2.395, P=0.031, 95% CI: 1.087-5.274), CRP (OR=3.864, P=0.004, 95% CI: 1.563-3.864), PCT (OR=4.125, P=0.001, 95% CI: 1.793-3.864), and D-D (OR=3.920, P=0.002, 95% CI: 1.632-3.864) were independent risk factors for plastic bronchitis in children with mycoplasma pneumoniae infection (P<0.05). Conclusion Age, allergy history, NE%, CRP, PCT and D-D are independent risk factors for plastic bronchitis in children with mycoplasma pneumoniae infection . It is necessary to take clinical intervention measures to reduce the occurrence risk.
3.Nusinersen combined with risdiplam for the treatment of spinal muscular atrophy: a case series of 10 patients and literature review.
Hao-Lin DUAN ; Ci-Liu ZHANG ; Li-Fen YANG ; Fang HE ; Lei-Lei MAO ; Jing PENG
Chinese Journal of Contemporary Pediatrics 2025;27(4):458-464
OBJECTIVES:
To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA).
METHODS:
A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University.
RESULTS:
Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention.
CONCLUSIONS
Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans
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Oligonucleotides/adverse effects*
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Male
;
Female
;
Child, Preschool
;
Retrospective Studies
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Infant
;
Muscular Atrophy, Spinal/drug therapy*
;
Drug Therapy, Combination
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Child
;
Azo Compounds
;
Pyrimidines
4.Febrile infection-related epilepsy syndrome caused by hemophagocytic lymphohistiocytosis: a case report.
Xiao-Lu DENG ; Li-Fen YANG ; Xia WANG ; Hui ZHANG ; Jian HE ; Jing PENG
Chinese Journal of Contemporary Pediatrics 2025;27(7):864-869
The patient was a girl, aged 10 years, who was admitted due to fever for 5 days and pancytopenia in peripheral blood for 2 days. Bone marrow examination showed the presence of phagocytic activity, and peripheral blood tests showed pancytopenia, an increase in ferritin, a reduction in fibrinogen, increases in triglyceride and sCD25, and a reduction in natural killer cell activity, which led to the diagnosis of hemophagocytic lymphohistiocytosis (HLH). On the day of admission, the child developed convulsions and rapidly progressed to refractory status epilepticus, which was consistent with the manifestations of febrile infection-related epilepsy syndrome. HLH was controlled after active immunotherapy, with the sequela of refractory epilepsy, and her cognitive function was essentially within normal limits. This article reports the condition of febrile infection-related epilepsy syndrome caused by HLH for the first time in China, in order to improve the awareness of this disease among clinicians.
Humans
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Lymphohistiocytosis, Hemophagocytic/complications*
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Female
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Child
;
Epilepsy/etiology*
;
Fever/etiology*
;
Epileptic Syndromes/etiology*
5.Clinical Characteristics and Prognosis of Primary Pulmonary Lymphoma.
You-Fan FENG ; Yuan-Yuan ZHANG ; Xiao Fang WEI ; Qi-Ke ZHANG ; Li ZHAO ; Xiao-Qin LIANG ; Yuan FU ; Fei LIU ; Yang-Yang ZHAO ; Xiu-Juan HUANG ; Qing-Fen LI
Journal of Experimental Hematology 2025;33(2):387-392
OBJECTIVE:
To investigate the clinical characteristics and prognosis of primary pulmonary lymphoma (PPL).
METHODS:
The clinical data of 17 patients with PPL admitted to Gansu Provincial Hospital from January 2013 to June 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized.
RESULTS:
The median age of the 17 patients was 56 (29-73) years old. There were 8 males and 9 females. According to Ann Arbor staging system, there were 9 patients with stage I-II and 8 patients with stage III-IV. There were 14 patients with IPI score of 0-2 and 3 patients with IPI score of 3-4. All 17 patients had symptoms at the initial diagnosis, most of the first symptoms were cough, and 6 patients had B symptoms.Among the 17 patients, there were 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, 1 case of gray zone lymphoma (GZL), and 3 cases of Hodgkin's lymphoma (HL). 15 patients received chemotherapy, of which 3 cases received autologous hematopoietic stem cell transplantation(ASCT) and 3 cases received radiotherapy; 2 patients did not receive treatment. The median number of chemotherapy courses was 6(2-8). The short-term efficacy was evaluated, 12 patients achieved complete remission (CR) and 3 patients achieved partial remission (PR). The age, pathological subtype, sex, Ann Arbor stage, β2-microglobulin(β2-MG) level, lactate dehydrogenase(LDH) level were not correlated with CR rate (P >0.05), while IPI score was correlated with recent CR rate (P < 0.05 ). The median follow-up time was 31(2-102) months. One of the 12 CR patients died of COVID-19, and the rest survived. Among the 3 patients who did not reach CR, 1 died after disease progression, while the other 2 survived. One of the 2 untreated patients died one year after diagnosis. Both the median progression-free survival (PFS) time and overall survival (OS) time of the 17 patients were both 31 (2-102) months.
CONCLUSION
The incidence of PPL is low, and the disease has no specific clinical manifestations, which is easily missed and misdiagnosed. The pathological subtypes are mainly MALT lymphoma and DLBCL, and the treatment is mainly combined chemotherapy. The IPI score is related to the treatment efficacy.
Humans
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Middle Aged
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Male
;
Female
;
Adult
;
Prognosis
;
Aged
;
Lung Neoplasms/therapy*
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Retrospective Studies
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Neoplasm Staging
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Lymphoma/therapy*
;
Lymphoma, Large B-Cell, Diffuse
6.Tongmai Hypoglycemic Capsule Attenuates Myocardial Oxidative Stress and Fibrosis in the Development of Diabetic Cardiomyopathy in Rats.
Jie-Qiong ZENG ; Hui-Fen ZHOU ; Hai-Xia DU ; Yu-Jia WU ; Qian-Ping MAO ; Jun-Jun YIN ; Hai-Tong WAN ; Jie-Hong YANG
Chinese journal of integrative medicine 2025;31(3):251-260
OBJECTIVE:
To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats.
METHODS:
A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively.
RESULTS:
Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01).
CONCLUSION
THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals
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Diabetic Cardiomyopathies/physiopathology*
;
Oxidative Stress/drug effects*
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Drugs, Chinese Herbal/therapeutic use*
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Rats, Sprague-Dawley
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Myocardium/metabolism*
;
Fibrosis
;
Male
;
Capsules
;
Hypoglycemic Agents/therapeutic use*
;
NF-E2-Related Factor 2/metabolism*
;
Rats
;
Diabetes Mellitus, Experimental/drug therapy*
7.Effect of Modified Chaihu Shugansan on CaMKⅡ/CREB Signaling Pathway in Rats with Myocardial Ischemia and Depression
Fen WAN ; Xiaohong LI ; Ying CHEN ; Yangyu PAN ; Yanna LUO ; Fangge LU ; Chuncheng ZHENG ; Pengyun KONG ; Chengxiang WANG ; Liqiang YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):1-11
ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/cAMP-response element binding protein (CREB) signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet, intraperitoneal injection of isoproterenol (ISO), and chronic unpredictable mild stress (CUMS). A total of 108 SD male rats were randomly divided into normal group, model group, high (23.4 g·kg-1), medium (11.7 g·kg-1), and low (5.85 g·kg-1) dose groups of modified Chaihu Shugansan, CaMKⅡ inhibitor (KN93) group, and KN93 + high, medium, and low dose groups of modified Chaihu Shugansan, with 12 rats in each group. From the first day of modeling to the end of modeling, drugs were administered once a day. In the seventh and eighth weeks, the KN93 group and the KN93 + high, medium, and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week, behavioral tests including sucrose preference, open field, and elevated plus maze were conducted. Electrocardiogram (ECG) lead Ⅱ changes were observed in each group of rats, and hematoxylin-eosin (HE) staining was performed to observe changes in heart tissue. Serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lactate dehydrogenase (LDH) were measured by using an enzyme-labeled instrument. Creatine kinase (CK) and creatine kinase-MB (CK-MB) were detected by ultraviolet spectrophotometry, while serum monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue, and Western blot was performed to assess protein expression of CaMKⅡ, phosphorylated (p)-CaMKⅡ, CREB, and p-CREB. ResultsCompared to the normal group, the model group showed significant reductions in sucrose preference rate, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01). The ECG showed ST-segment elevation, and HE staining showed serious degeneration of myocardial fibers, disordered arrangement, and infiltration of a large number of inflammatory cells. In addition, serum TC and LDL levels increased (P<0.01), and HDL level decreased (P<0.01). CK, CK-MB, LDH, and MCP-1 levels significantly increased (P<0.05, P<0.01). The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue (P<0.05, P<0.01), but those increased in the heart tissue (P<0.01). Compared to the model group, the high, medium, and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference, total activity distance in the open field, number of entries into the center area of the open field, and percentage of entries into the open arms of the elevated plus maze (P<0.01), as well as decreased serum CK, CK-MB, LDH, and MCP-1 levels (P<0.05, P<0.01). KN93 also reduced ST-segment elevation, alleviated the degeneration degree of myocardial fibrosis, and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced (P<0.05, P<0.01). The KN93 + high, medium, and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression, possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway, with the high-dose modified Chaihu Shugansan showing the best effects.
8.Association of NLRP3 genetic variant rs10754555 with early-onset coronary artery disease.
Lingfeng ZHA ; Chengqi XU ; Mengqi WANG ; Shaofang NIE ; Miao YU ; Jiangtao DONG ; Qianwen CHEN ; Tian XIE ; Meilin LIU ; Fen YANG ; Zhengfeng ZHU ; Xin TU ; Qing K WANG ; Zhilei SHAN ; Xiang CHENG
Chinese Medical Journal 2025;138(21):2844-2846
9.Metabolomics and pharmacokinetics of Corni Fructus in ameliorating myocardial ischemic injury.
Xiang-Feng LIU ; Yu WU ; Chao-Yan YANG ; Hua-Wei LIAO ; Yan-Fen CHEN ; Xin HE ; Ying-Fang WANG ; Jin-Ru LIANG
China Journal of Chinese Materia Medica 2025;50(5):1363-1376
This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals
;
Cornus/chemistry*
;
Mice
;
Metabolomics
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Myocardial Ischemia/metabolism*
;
Humans
;
Troponin I/metabolism*
;
Myocardium/pathology*
;
Disease Models, Animal
;
Biomarkers/metabolism*
;
Creatine Kinase, MB Form/metabolism*
10.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.


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