39 results on '"Hui-hua Li"'
Search Results
2. The role of the immunoproteasome in cardiovascular disease
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Yifei Nie, Zhao Ma, Baoen Zhang, Meichen Sun, Dongfeng Zhang, Hui-Hua Li, and Xiantao Song
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Immunoproteasome ,Cardiovascular disease ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The ubiquitinproteasome system (UPS) is the main mechanism responsible for the intracellular degradation of misfolded or damaged proteins. Under inflammatory conditions, the immunoproteasome, an isoform of the proteasome, can be induced, enhancing the antigen-presenting function of the UPS. Furthermore, the immunoproteasome also serves nonimmune functions, such as maintaining protein homeostasis and regulating signalling pathways, and is involved in the pathophysiological processes of various cardiovascular diseases (CVDs). This review aims to provide a comprehensive summary of the current research on the involvement of the immunoproteasome in cardiovascular diseases, with the ultimate goal of identifying novel strategies for the treatment of these conditions.
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- 2024
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3. CD11b mediates hypertensive cardiac remodeling by regulating macrophage infiltration and polarization
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Yun-Long Zhang, Jie Bai, Wei-Jia Yu, Qiu-Yue Lin, and Hui-Hua Li
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Integrin CD11b ,Hypertensive stimuli ,Cardiac remodeling ,Macrophage infiltration and polarization ,Medicine (General) ,R5-920 ,Science (General) ,Q1-390 - Abstract
Introduction: Leukocyte infiltration is an early event during cardiac remodeling frequently leading to heart failure (HF). Integrins mediate leukocyte infiltration during inflammation. However, the importance of specific integrins in hypertensive cardiac remodeling is still unclear. Objectives: To elucidate the significance of CD11b in hypertensive cardiac remodeling. Methods: Angiotensin (Ang II) or deoxycorticosterone acetate (DOCA)-salt was used to induce cardiac remodeling in mice of gene knockout (KO), bone marrow (BM) chimera, and the CD11b neutralizing antibody or agonist leukadherin-1 (LA1) treatment. Results: Our microarray data showed that integrin subunits Itgam (CD11b) and Itgb2 (CD18) were the most highly upregulated in Ang II-infused hearts. CD11b expression and CD11b/CD18+ myelomonocytes were also time-dependently increased. KO or pharmacological blockade of CD11b greatly attenuated cardiac remodeling and macrophage infiltration and M1 polarization induced by Ang II or DOCA-salt. This protection was verified in wild-type mice transplanted with CD11b-deficient BM cells. Conversely, administration of CD11b agonist LA1 showed the opposite effects. Further, CD11b KO reduced Ang II-induced macrophage adhesion and M1 polarization, leading to reduction of cardiomyocyte enlargement and fibroblast differentiation in vitro. The numbers of CD14+CD11b+CD18+ monocytes and CD15+CD11b+CD18+ granulocytes were obviously higher in HF patients than in normal controls. Conclusion: Our data demonstrate an important role of CD11b+ myeloid cells in hypertensive cardiac remodeling, and suggest that HF may benefit from targeting CD11b.
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- 2024
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4. Myeloid ACE2 protects against septic hypotension and vascular dysfunction through Ang-(1–7)-Mas-mediated macrophage polarization
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Jia-Xin Li, Xue Xiao, Fei Teng, and Hui-Hua Li
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Sepsis ,ACE2 ,Macrophage polarization ,Hypotension ,Vascular dysfunction ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Angiotensin converting enzyme 2 (ACE2) is a new identified member of the renin-angiotensin-aldosterone system (RAAS) that cleaves angiotensin II (Ang II) to Ang (1–7), which exerts anti-inflammatory and antioxidative activities via binding with Mas receptor (MasR). However, the functional role of ACE2 in sepsis-related hypotension remains unknown. Our results indicated that sepsis significantly reduced blood pressure and led to disruption between ACE-Ang II and ACE2-Ang (1–7) balance. ACE2 knock-in mice exhibited improved sepsis-induced mortality, hypotension and vascular dysfunction, while ACE2 knockout mice exhibited the opposite effects. Bone marrow transplantation and in vitro experiments confirmed that myeloid ACE2 exerted a protective role by suppressing oxidative stress, NO production and macrophage polarization via the Ang (1–7)-MasR–NF–κB and STAT1 pathways. Thus, ACE2 on myeloid cells could protect against sepsis-mediated hypotension and vascular dysfunction, and upregulating ACE2 may represent a promising therapeutic option for septic patients with hypotension.
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- 2024
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5. Caffeine intake interacts with Asian gene variants in Parkinson's disease: a study in 4488 subjectsResearch in context
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Yi-Lin Ong, Xiao Deng, Hui-Hua Li, K. Narasimhalu, Ling-Ling Chan, Kumar M. Prakash, Wing-Lok Au, Pavanni Ratnagopal, Louis C.S. Tan, and Eng-King Tan
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Parkinsons disease ,LRRK2 ,Caffeine ,Gene-caffeine ,Public aspects of medicine ,RA1-1270 - Abstract
Summary: Background: Caffeine intake reduces risk of Parkinson's disease (PD), but the interaction with genes is unclear. The interaction of caffeine with genetic variants in those at high PD risk has healthcare importance. We investigate interactions of caffeine intake with risk variants found in Asians, and determine PD risk estimates in caffeine-drinkers carrying these variants. Methods: PD patients and controls without neurological disorders were included. Caffeine intake was assessed using a validated evaluation tool. Leucine rich repeat kinase 2 (LRRK2) risk variants were genotyped. Statistical analysis was conducted with logistic regression models. Gene-caffeine interactions were quantified using attributable proportion (AP) due to interaction (positive interaction defined as AP >0). Findings: 5100 subjects were screened and 4488 subjects (1790 PD, 2698 controls) with genetic data of at least one LRRK2 variant were included. Risk-variant-carriers who were non-caffeine-drinkers had increased PD odds compared to wildtype carriers who were caffeine-drinkers for G2385R [OR 8.6 (2.6–28.1) p
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- 2023
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6. Research Progress of Hippocampal Dopamine System Changes in Perioperative Neurocognitive Disorders
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Feng-Nian Jia, An-Ran Chen, Hui-Hua Li, and Cui-Cui Yu
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perioperative neurocognitive disorders ,hippocampus ,dopamine ,anesthesia ,sevoflurane ,isoflurane ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Perioperative neurocognitive disorders (PND) are a cognitive impairment that occurs after anesthesia, especially in elderly patients and significantly affects their quality of life. The hippocampus, as a critical region for cognitive function and an important location in PND research, has recently attracted increasing attention. However, in the hippocampus the impact of anesthesia and its underlying mechanisms remain unclear. This review focuses on investigation of the effects of anesthesia on the hippocampal dopamine (DA) system and explores its potential association with PND. Through comprehensive review of existing studies, it was found that anesthesia affects the hippocampus through various pathways involved in metabolism, synaptic plasticity and oxygenation. Anesthesia may also influence the DA neurotransmitter system in the brain which plays a role in emotions, rewards, learning and memory functions. Specifically, anesthesia may participate in the pathogenesis of PND by affecting the DA system within the hippocampus. Future studies should explore the molecular mechanisms of these effects through techniques such as neuroimaging to study real-time effects to improve animal models to better simulate clinical observations. For clinical application, it is recommended that physicians exercise caution when selecting and managing anesthetic drugs by adopting comprehensive cognitive assessment methods to reduce post-anesthesia cognitive risk. Overall, this review provides a better understanding of the relationship between the hippocampal DA system and perioperative neurocognitive function and provides valuable guidance for prevention and treatment strategies for PND.
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- 2024
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7. Blockage of S100A8/A9 ameliorates septic nephropathy in mice
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Wei Shi, Tian-Tian Wan, Hui-Hua Li, and Shu-Bin Guo
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acute kidney injury ,Paquinimod ,mitochondrial dynamics ,S100A8/A9 ,sepsis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Septic acute kidney injury (AKI) is the commonest cause of complication of sepsis in intensive care units, but its pathophysiology remains unclear. Calprotectin (S100A8/A9), which is a damage-associated molecular patterns (DAMPs) molecule, exerts a critical role in modulating leukocyte recruitment and inflammatory response during various diseases. However, role of S100A8/A9 in septic AKI is largely unknown. In this research, Septic AKI was triggered by cecal ligation and puncture (CLP) operation in wild-type mice, which treated with or without an S100A9 inhibitor, Paquinimod (Paq, 10 mg/kg) that prevents S100A8/A9 to bind to Toll-like receptor 4 (TLR4). Renal function, pathological changes, cell death, and oxidative stress were evaluated. Our research indicated that the mRNA and protein expression of S100A9 are time-dependently elevated in the kidney following CLP. Moreover, the administration of Paq for 24 h significantly improved CLP-induced renal dysfunction and pathological alterations compared with vehicle treatment in mice. These beneficial effects were associated with the inhibition of CLP-triggered renal tubular epithelial cell apoptosis, inflammation, superoxide production, and mitochondrial dynamic imbalance. What’s more, we further confirmed the above findings by cell co-culture experiments. Our study demonstrates that S100A9 is a prominent protein to lead to septic AKI, and the selective inhibition of S100A9 could represent a new therapeutic approach which can treat septic AKI.
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- 2023
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8. Serial deep gray nuclear DTI changes in Parkinson’s disease over twelve years
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Yao-Chia Shih, Leon Qi Rong Ooi, Hui-Hua Li, John Carson Allen, Septian Hartono, Thomas Welton, Eng-King Tan, and Ling Ling Chan
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Parkinson’s disease ,basal ganglia ,diffusion tensor imaging (DTI) ,longitudinal ,neurodegeneration ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
BackgroundDeep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson’s disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years.MethodsParticipating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time.ResultsMD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores.ConclusionPallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.
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- 2023
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9. MK-886 protects against cardiac ischaemia/reperfusion injury by activating proteasome-Keap1-NRF2 signalling
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Kai-Na Shi, Pang-Bo Li, Hui-Xiang Su, Jing Gao, and Hui-Hua Li
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MK-886 ,Myocardial ischaemia/reperfusion injury ,Immunoproteasome ,Keap1/NRF2 ,Mitochondrial dynamics ,Oxidative stress ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Oxidative stress is considered a key factor contributing to the initiation and development of cardiac injury following ischaemia‒reperfusion (I/R). Arachidonate 5-lipoxygenase (ALOX5) is a rate-limiting enzyme for leukotriene biosynthesis. MK-886 is an inhibitor of ALOX5 that exhibits anti-inflammatory and antioxidant activities. However, the significance of MK-886 in preventing I/R-mediated cardiac injury and the underlying mechanism remain unclear. Cardiac I/R model was produced by ligation/release of the left anterior descending artery. MK-886 (20 mg/kg) was administered intraperitoneally into mice at 1 and 24 h before I/R. Our results indicated that MK-886 treatment significantly attenuated I/R-mediated cardiac contractile dysfunction and decreased the infarct area, myocyte apoptosis, and oxidative stress accompanied with reduction of Kelch-like ECH-associated protein 1 (keap1) and upregulation of nuclear factor erythroid 2-related factor 2 (NRF2). Conversely, administration of the proteasome inhibitor epoxomicin and NRF2 inhibitor ML385 greatly abrogated MK-886-mediated cardioprotection after I/R injury. Mechanistically, MK-886 enhanced the expression of the immunoproteasome subunit β5i, which interacted with keap1 and enhanced its degradation, leading to activation of the NRF2-dependent antioxidant response and improvement of mitochondrial fusion-fission balance in the I/R-treated heart. In summary, our present findings indicated that MK-886 could protect the heart against I/R injury and highlight that MK-886 may represent a promising therapeutic candidate for preventing ischaemic disease.
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- 2023
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10. The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention
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Chao Ren, Peng Zhang, Xiao-Yan Yao, Hui-Hua Li, Rui Chen, Cai-Yi Zhang, and De-Qin Geng
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Cognition ,DKK1 ,Fluoride ,Drinking water ,Risk factors ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Objective To evaluate cognitive impairment and risk factors of elders in high fluoride drinking water areas and investigate whether DKK1 is involved in this disorder. Methods MoCA-B and AD-8 were used to measure the cognitive functions of 272 and 172 subjects over the age of 60 came from the high and normal fluoride drinking water areas respectively, general information and peripheral blood were collected, the level of SOD, GSH and MDA were measured, mRNA level of DKK1, the concentration of blood fluoride and the polymorphism of APOE were tested. Results The blood fluoride concentration, mRNA level of DKK1 and ratio of abnormal cognitive function of subjects in high fluorine drinking water areas were higher than those in normal areas. The level of SOD of subjects in high fluorine drinking water was low compared with those in normal areas. The level of MDA and GSH had no difference between the two crowds in different fluorine drinking water areas. There were differences in cigarette smoking, education, dental status, hypertension, hyperlipidaemia and APOE results between the two crowds in different fluorine drinking water areas. The mRNA level of DKK1 and the level of cognitive function showed a positive correlation and DKK1 was one of five risk factors involved in cognitive impairment of older people living in high fluorosis areas. Conclusions The cognitive functions could be impaired in the older people living in high fluoride drinking water areas, and DKK1 may as a potential intervention point of this brain damage process need attention.
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- 2021
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11. Cardiac-specific CGI-58 deficiency activates the ER stress pathway to promote heart failure in mice
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Xin Xie, Yi-Fan Tie, Song Lai, Yun-Long Zhang, Hui-Hua Li, and Ying Liu
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Cytology ,QH573-671 - Abstract
Abstract Excess myocardial triacylglycerol accumulation (i.e., cardiac steatosis) impairs heart function, suggesting that enzymes promoting triacylglycerol metabolism exert essential regulatory effects on heart function. Comparative gene identification 58 (CGI-58) is a key enzyme that promotes the hydrolysis of triglycerides by activating adipose triglyceride lipase and plays a protective role in maintaining heart function. In this study, the effects of CGI-58 on heart function and the underlying mechanism were investigated using cardiac-specific CGI58-knockout mice (CGI-58cko mice). Echocardiography and pathological staining were performed to detect changes in the structure and function of the heart. Proteomic profiling, immunofluorescent staining, western blotting, and real-time PCR were used to evaluate molecular changes. In CGI-58cko mice, we detected cardiac hypertrophic remodeling and heart failure associated with excessive cardiac lipid accumulation, ROS production, and decreased expression of regulators of fatty acid metabolism. These changes were markedly attenuated in CGI-58cko mice injected with rAAV9-CGI58. A quantitative proteomics analysis revealed significant increases in the expression of ER stress-related proteins and decreases in proteins related to fatty acid and amino acid metabolism in the hearts of CGI-58cko mice. Furthermore, the inhibition of ER stress by the inhibitor 4-PBA improved mitochondrial dysfunction, reduced oxidative stress, and reversed cardiac remodeling and dysfunction in cultured cardiomyocytes or in CGI-58cko mice. Our results suggested that CGI-58 is essential for the maintenance of heart function by reducing lipid accumulation and ER stress in cardiomyocytes, providing a new therapeutic target for cardiac steatosis and dysfunction.
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- 2021
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12. Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice
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Yu-Hui Gu, Kai-Wen Ren, Yu Wang, Shi-Hao Wang, Xiao-Hong Yu, Li-Wen Xu, Hui-Hua Li, and Hai-Lian Bi
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cardiac remodeling ,USP7 inhibitor ,P22077 ,inflammation ,oxidase stress ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Hypertension is one of the common causes of pathological cardiac hypertrophy and a major risk for morbidity and mortality of cardiovascular diseases worldwide. Ubiquitin-Specific Protease 7 (USP7), the first identified deubiquitinating enzymes, participated in a variety of biological processes, such as cell proliferation, DNA damage response, tumourigenesis, and apoptosis. However, its role and mechanism in cardiac remodeling remain unclear. Here, our data indicated that USP7 expression was increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure, while the administration of its inhibitor p22077 attenuated cardiac hypertrophy, cardiac fibrosis, inflammation, and oxidase stress. Mechanistically, the administration of p22077 inhibited the multiple signaling pathways, including AKT/ERK, TGF-β/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). Taken together, these findings demonstrate that USP7 may be a new therapeutic target for hypertrophic remodeling and HF.
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- 2022
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13. Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice
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Kai-Wen Ren, Xiao-Hong Yu, Yu-Hui Gu, Xin Xie, Yu Wang, Shi-hao Wang, Hui-Hua Li, and Hai-Lian Bi
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atrial fibrillation ,atrial inflammation ,atrial fibrosis ,Bhlhe40 ,NLRP3 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Atrial fibrosis and atrial inflammation are associated with the pathogenesis of atrial fibrillation (AF). Basic helix–loop–helix family member E40 (Bhlhe40) is an important transcription factor, which is involved in tumors, inflammation, apoptosis, viral infection, and hypoxia. However, its role and molecular mechanism in AF remain unclear. In this study, a mouse model of AF was induced by Ang II infusion. The atrial diameter was evaluated using echocardiography. Induction and duration of AF were measured by programmed electrical stimulation. Atrial structural remodeling was detected using routine histologic examinations. Our results showed that Bhlhe40 was significantly upregulated in angiotensin II (Ang II)-stimulated atrial cardiomyocytes and atrial tissues and in tissues from patients with AF. Cardiac-specific knockdown of Bhlhe40 in mice by a type 9 recombinant adeno-associated virus (rAAV9)-shBhlhe40 significantly ameliorated Ang II-induced atrial dilatation, atrial fibrosis, and atrial inflammation, as well as the inducibility and duration of AF. Mechanistically, cardiac-specific knockdown of Bhlhe40 attenuated Ang II-induced activation of NF-κB/NLRP3, TGF-1β/Smad2 signals, the increased expression of CX43, and the decreased expression of Kv4.3 in the atria. This is the first study to suggest that Bhlhe40 is a novel regulator of AF progression, and identifying Bhlhe40 may be a new therapeutic target for hypertrophic remodeling and heart failure.
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- 2022
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14. CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration
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Shuai Wang, Jie Bai, Yun-Long Zhang, Qiu-Yue Lin, Xiao Han, Wei-Kun Qu, Peng-Fei Zhang, Yu-Song Ge, Qi Zhao, and Hui-Hua Li
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Hypertensive retinopathy ,CXCL1 ,CXCR2 ,Macrophages ,Inflammation ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Inflammation plays an important role in hypertensive retinal vascular injury and subsequent retinopathy. Monocyte chemotaxis via CXCL1-CXCR2 binding has been implicated in various cardiovascular diseases, but the function of CXCL1-CXCR2 signalling involved in retinopathy, which was investigated as angiotensin II (Ang II)-induced retinopathy, is unclear. In our study, we established a hypertensive retinopathy (HR) model by Ang II infusion (3000 ng/min/kg) for 3 weeks. To determine the involvement of CXCR2 signalling, we used CXCR2 knockout (KO) mice or C57BL/6J wild-type (WT) mice as experimental subjects. The mice were treated with a CXCL1 neutralizing antibody or SB225002 (the specific CXCR2 inhibitor). Our results showed that after Ang II treatment, the mRNA levels of CXCL1 and CXCR2 and the number of CXCR2+ inflammatory cells were significantly elevated. Conversely, unlike in the IgG control group, the CXCL1 neutralizing antibody greatly reduced the increase in central retinal thickness induced by Ang II infusion, arteriolar remodelling, superoxide production, and retinal dysfunction in WT mice. Furthermore, Ang II infusion induced arteriolar remodelling, infiltration of Iba1+ macrophages, the production of oxidative stress, and retinal dysfunction, but the symptoms were ameliorated in CXCR2 KO mice and SB225002-treated mice. These protective effects were related to the reduction in the number of CXCR2+ immune cells, particularly macrophages, and the decrease in proinflammatory cytokine (IL-1β, IL-6, TNF-ɑ, and MCP-1) expression in Ang II-treated retinas. Notably, serum CXCL1 levels and the number of CXCR2+ monocytes/neutrophils were higher in HR patients than in healthy controls. In conclusion, this study provides new evidence that the CXCL1-CXCR2 axis plays a vital role in the pathogenesis of hypertensive retinopathy, and selective blockade of CXCL1-CXCR2 activation may be a potential treatment for HR.
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- 2022
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15. Effects of chronic fluorosis on the brain
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Chao Ren, Hui-Hua Li, Cai-Yi Zhang, and Xi-Cheng Song
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Environmental toxins ,Public health ,Drinking water ,Fluorosis ,Brain damage ,Environmental pollution ,TD172-193.5 ,Environmental sciences ,GE1-350 - Abstract
This article reviews the effects of chronic fluorosis on the brain and possible mechanisms. We used PubMed, Medline and Cochraine databases to collect data on fluorosis, brain injury, and pathogenesis. A large number of in vivo and in vitro studies and epidemiological investigations have found that chronic fluorosis can cause brain damage, resulting in abnormal brain structure and brain function.Chronic fluorosis not only causes a decline in concentration, learning, and memory, but also has mental symptoms such as anxiety, tension, and depression. Several possible mechanisms that have been proposed: the oxidative stress and inflammation theory, neural cell apoptosis theory, neurotransmitter imbalance theory, as well as the doctrine of the interaction of fluorine with other elements. However, the specific mechanism of chronic fluorosis on brain damage is still unclear. Thus, a better understanding of the mechanisms via which chronic fluorosis causes brain damage is of great significance to protect the physical and mental health of people in developing countries, especially those living in the endemic areas of fluorosis. In brief, further investigation concerning the influence of fluoride on the brain should be conducted as the neural damage induced by it may bring about a huge problem in public health, especially considering growing environmental pollution.
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- 2022
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16. Time Series Transcriptomic Analysis by RNA Sequencing Reveals a Key Role of PI3K in Sepsis-Induced Myocardial Injury in Mice
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Xiao Yan, Yun-Long Zhang, Xiao Han, Pang-Bo Li, Shu-Bin Guo, and Hui-Hua Li
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cecal ligation and puncture ,septic cardiomyopathy ,RNA sequencing ,time series gene expression profiling ,PIK3R5 ,Physiology ,QP1-981 - Abstract
Septic cardiomyopathy is the main complication and cause of death of severe sepsis with limited therapeutic strategy. However, the molecular mechanism of sepsis-induced cardiac injury remains unclear. The present study was designed to investigate differentially expressed genes (DEGs) involved in the pathogenesis of septic cardiomyopathy induced by cecal ligation and puncture (CLP) in mice. Male C57BL/6J mice (8–10 weeks old) were subjected to CLP with 21-gauge needles for 24, 48, and 72 h. Myocardial function was assessed by echocardiography. The pathological changes of the heart were evaluated by hematoxylin and eosin as well as immunohistochemical staining. Time series RNA sequencing was utilized to investigate the gene expression profiles. CLP surgery resulted in a significant decrease of animal survival rate and left ventricle contractile function, and an increase in cardiac dilation and infiltration of proinflammatory cells including Mac-2+ macrophages in a time-dependent manner. RNA sequencing identified 5,607 DEGs in septic myocardium at 24, 48, and 72 h after CLP operation. Moreover, gene ontology analysis revealed that these DEGs were mainly associated with the biological processes, including cell adhesion, immune system process, inflammatory response, and positive regulation of cell migration. KEGG pathway enrichment analysis indicated that Staphylococcus aureus infection, osteoclast differentiation, leishmaniasis, and ECM-receptor interaction were significantly altered in septic hearts. Notably, Pik3r1 and Pik3r5 were localized in the center of the gene co-expression network, and were markedly upregulated in CLP-induced septic myocardium. Further, blocking PI3Kγ by the specific inhibitor CZC24832 significantly protected against sepsis-induced cardiac impairment. The present study uncovers the gene expression signatures of CLP-induced myocardial injury and sheds light on the role of Pik3r5 in septic cardiomyopathy.
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- 2022
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17. Ursolic Acid Ameliorates Myocardial Ischaemia/Reperfusion Injury by Improving Mitochondrial Function via Immunoproteasome-PP2A-AMPK Signalling
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Luo-Luo Xu, Hui-Xiang Su, Pang-Bo Li, and Hui-Hua Li
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myocardial ischaemia/reperfusion ,ursolic acid ,immunoproteasome ,mitochondrial function ,PP2A ,AMPK ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Cardiac ischaemia/reperfusion (I/R) injury causes cardiomyocyte apoptosis and mitochondrial dysfunction. Ursolic acid (UA), as a pentacyclic triterpenoid carboxylic acid, exerts several bioactivities in animal models of different diseases, but the preventive role of UA in I/R-induced myocardial dysfunction remains largely unknown. Male wild-type mice were pre-administered with UA at a dosage of 80 mg/kg i.p. and then subjected to cardiac I/R injury for 24 h. Cardiac function and pathological changes were examined by echocardiography and histological staining. The protein and mRNA levels of the genes were determined using qPCR and immunoblotting analysis. Our results revealed that UA administration in mice significantly attenuated the I/R-induced decline in cardiac function, infarct size, myocyte apoptosis, and oxidative stress. Mechanistically, UA increased three immunoproteasome catalytic subunit expressions and activities, which promoted ubiquitinated PP2A degradation and activated AMPK-PGC1α signalling, leading to improved mitochondrial biosynthesis and dynamic balance. In vitro experiments confirmed that UA treatment prevented hypoxia/reperfusion (H/R)-induced cardiomyocyte apoptosis and mitochondrial dysfunction through activation of AMPK signalling. In summary, our findings identify UA as a new activator of the immunoproteasome that exerts a protective role in I/R-induced myocardial dysfunction and suggest that UA supplementation could be beneficial for the prevention of cardiac ischaemic disease.
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- 2023
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18. Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice
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Liangqingqing Yin, Jie Bai, Wei-Jia Yu, Ying Liu, Hui-Hua Li, and Qiu-Yue Lin
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VCAM-1 ,hypertension ,macrophage adhesion ,inflammation ,oxidative stress ,vascular dysfunction ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Adhesion of monocytes to the vascular endothelium frequently leads to an inflammatory response, which contributes to hypertension and vascular remodeling. Vascular cellular adhesion molecule-1 (VCAM-1) plays an important role in leukocyte adhesion and migration during inflammatory diseases. However, its role in angiotensin (Ang) II -induced hypertension and vascular dysfunction remains largely unknown. Wild-type (WT) mice were administered a VCAM-1 neutralizing antibody (0.1 or 0.2 mg/mouse/day) or IgG control and then infused with Ang II (490 ng kg−1 min−1) or saline continuously for 14 days. Systolic blood pressure (SBP) was measured with a tail-cuff system, pathological changes in the aorta were assessed by histological staining, and vascular relaxation was analyzed an aortic ring assay. Our results indicated that compared with saline infusion, Ang II infusion significantly upregulated VCAM-1 expression in the mouse aorta and serum. Moreover, Ang II infusion markedly increased arterial hypertension, wall thickness, fibrosis, infiltration of Mac-2+ macrophages, reactive oxygen species (ROS) production and vascular relaxation dysfunction. Conversely, blockade of VCAM-1 with a neutralizing antibody substantially alleviated these effects. In vitro experiments further confirmed that the VCAM-1 neutralizing antibody inhibited Ang II-induced macrophage adhesion and migration and DNA damage and oxidative stress in endothelial cells (ECs). In conclusion, these results indicate that blockade of VCAM-1 exerts a protective effect against Ang II-induced arterial hypertension and dysfunction by regulating monocytes adhesion and infiltration into the endothelium and represents a novel therapeutic approach for hypertension.
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- 2022
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19. Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins
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Hui-Hua Li, Monte S. Willis, Pamela Lockyer, Nathaniel Miller, Holly McDonough, David J. Glass, and Cam Patterson
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Medicine - Published
- 2022
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20. Correction: Transcriptional Effects of E3 Ligase Atrogin-1/MAFbx on Apoptosis, Hypertrophy and Inflammation in Neonatal Rat Cardiomyocytes.
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Yong Zeng, Hong-Xia Wang, Shu-Bin Guo, Hui Yang, Xiang-Jun Zeng, Quan Fang, Chao-Shu Tang, Jie Du, and Hui-Hua Li
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0053831.].
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- 2022
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21. Corrigendum to: ‘Rituximab prevents and reverses cardiac remodeling by depressing B cell function in mice’ [Biomed. Pharmacother. 114 (2019) 108804]
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Xiao-Lei Ma, Qiu-Yue Lin, Lei Wang, Xin Xie, Yun-Long Zhang, and Hui-Hua Li
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Therapeutics. Pharmacology ,RM1-950 - Published
- 2021
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22. Integrin CD11b Contributes to Hypertension and Vascular Dysfunction Through Mediating Macrophage Adhesion and Migration
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Qiu-Yue Lin, Jie Bai, Yun-Long Zhang, and Hui-Hua Li
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Mice ,Integrins ,Angiotensin II ,Macrophages ,Hypertension ,Internal Medicine ,Animals - Abstract
Background: Leukocyte adhesion to endothelium is an early inflammatory response and is mainly controlled by the β2-integrins. However, the role of integrin CD11b/CD18 in the pathogenesis of hypertension and vascular dysfunction is unclear. Methods: Hypertension was established by angiotensin II (490 ng/kg·per min) or deoxycorticosterone acetate salt. Hypertensive responses were studied in CD11b-deficient (CD11b -/- ) mice, bone marrow transplanted and wild-type (WT) mice that were administered anti-CD11b neutralizing antibody or agonist leukadherin-1. Blood pressure was monitored with tail-cuff method and radiotelemetry. Blood and vascular inflammatory cells were assessed by flow cytometry. Aortic remodeling and function were examined using histology and aortic ring analysis. Cell adhesion and migration were evaluated in vitro. The relationship between circulating CD11b + immune cells and hypertension was analyzed in patients with hypertension. Results: We found that CD11b and CD18 expression as well as the CD45 + CD11b + CD18 + myeloid cells were highly increased in the aorta of angiotensin II-infused mice. Ablation or pharmacological inhibition of CD11b in mice significantly alleviated hypertension, aortic remodeling, superoxide generation, vascular dysfunction, and the infiltration of CD11b + macrophages through reducing macrophage adhesion and migration. These effects were confirmed in WT mice reconstituted with CD11b-deficient bone marrow cells. Conversely, angiotensin II-induced hypertensive response was exacerbated by CD11b agonist leukadherin-1. Notably, circulating CD45 + CD11b + CD18 + myeloid cells and the ligand levels in hypertensive patients were significantly higher than in normotensive controls. Conclusions: We demonstrated a critical significance of CD11b + myeloid cells in hypertension and vascular dysfunction. Targeting CD11b may represent a novel therapeutic option for hypertension.
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- 2023
23. Cardiac-specific Knockdown of DEC1 Regulated Pressure Overload-induced Cardiac Hypertrophy and Remodeling by Directly Inhibiting the Expression of PTEN
- Author
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Hai-Lian Bi, Xin Xie, Kai-Wen Ren, Xiao-Lei Yang, Qing-Xia Jia, Shi-Hao Wang, Hui-Hua Li, and Xiao-Hong Yu
- Abstract
Sustained cardiac hypertrophy is the onset of maladaptive myocardial remodeling and is a major cause of heart failure and sudden death. Recent studies have revealed that differentiated embryonic chondrocyte gene 1 (DEC1), a key transcription factor, is implicated in inflammation, hypoxia, viral infection, and tumors. However, its role and the molecular mechanism in cardiac hypertrophy and remodeling have not been fully elucidated. Here, our results showed that DEC1 was significantly upregulated in agonist-stimulated primary cardiomyocytes, in hypertrophic mice hearts and in human failure hearts. Cardiac specific knockdown of DEC1 using rAAV9 significantly attenuated TAC-induced cardiac hypertrophy and remodeling. Mechanistically, DEC1 bound directedly to the promoter region of PTEN, inhibited the transcriptional expression of PTEN, which subsequently increased the activation of AKT and its relative signaling pathway (including mTOR, NF-κB, and SMAD2), thereby causing cardiac hypertrophy, fibrosis, and inflammation. Furthermore, administration of the PTEN inhibitor VO-OHpic markedly reversed DEC1 knockdown-mediated attenuation of cardiomyocyte hypertrophy and cardiac remodeling. This is the first study to suggest that DEC1 regulates cardiac hypertrophy and remodeling by suppressing the expression of PTEN, and DEC1 may be a new therapeutic target for hypertrophic heart diseases.
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- 2023
24. CD11b mediates hypertensive cardiac remodeling by regulating macrophage infiltration and polarization
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Yun-Long Zhang, Jie Bai, Wei-Jia Yu, Qiu-Yue Lin, and Hui-Hua Li
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Multidisciplinary - Published
- 2023
25. Angiotensin II Induces Cardiac Edema and Hypertrophic Remodeling through Lymphatic-Dependent Mechanisms
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Jie Bai, Liangqingqing Yin, Wei-Jia Yu, Yun-Long Zhang, Qiu-Yue Lin, and Hui-Hua Li
- Subjects
Mice, Knockout ,Edema, Cardiac ,Proteasome Endopeptidase Complex ,Aging ,Article Subject ,Angiotensin II ,Myocardium ,Endothelial Cells ,Cardiomegaly ,Cell Biology ,General Medicine ,Vascular Endothelial Growth Factor Receptor-3 ,Biochemistry ,Permeability ,Mice ,cardiovascular system ,Animals ,Lymphangiogenesis ,Proteasome Inhibitors ,Lymphatic Vessels - Abstract
Cardiac lymphatic vessel growth (lymphangiogenesis) and integrity play an essential role in maintaining tissue fluid balance. Inhibition of lymphatic lymphangiogenesis is involved in cardiac edema and cardiac remodeling after ischemic injury or pressure overload. However, whether lymphatic vessel integrity is disrupted during angiotensin II- (Ang II-) induced cardiac remodeling remains to be investigated. In this study, cardiac remodeling models were established by Ang II (1000 ng/kg/min) in VEGFR-3 knockdown (Lyve-1Cre VEGFR-3f/−) and wild-type (VEGFR-3f/f) littermates. Our results indicated that Ang II infusion not only induced cardiac lymphangiogenesis and upregulation of VEGF-C and VEGFR-3 expression in the time-dependent manner but also enhanced proteasome activity, MKP5 and VE-cadherin degradation, p38 MAPK activation, and lymphatic vessel hyperpermeability. Moreover, VEGFR-3 knockdown significantly inhibited cardiac lymphangiogenesis in mice, resulting in exacerbation of tissue edema, hypertrophy, fibrosis superoxide production, inflammation, and heart failure (HF). Conversely, administration of epoxomicin (a selective proteasome inhibitor) markedly mitigated Ang II-induced cardiac edema, remodeling, and dysfunction; upregulated MKP5 and VE-cadherin expression; inactivated p38 MAPK; and reduced lymphatic vessel hyperpermeability in WT mice, indicating that inhibition of proteasome activity is required to maintain lymphatic endothelial cell (LEC) integrity. Our results show that both cardiac lymphangiogenesis and lymphatic barrier hyperpermeability are implicated in Ang II-induced adaptive hypertrophic remodeling and dysfunction. Proteasome-mediated hyperpermeability of LEC junctions plays a predominant role in the development of cardiac remodeling. Selective stimulation of lymphangiogenesis or inhibition of proteasome activity may be a potential therapeutic option for treating hypertension-induced cardiac remodeling.
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- 2022
26. Should mild OSA be treated? - A systematic review from the standpoint of disease progression
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Pei Yuan, Fong, Ze Yun, Tay, Rui Ya, Soh, Stephanie Man Chung, Fook, Hui Hua, Li, and Chu Qin, Phua
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- 2022
27. Time series proteome profile analysis reveals a protective role of citrate synthase in angiotensin II-induced atrial fibrillation
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Fei, Teng, Xiao, Han, Peng, Yu, Pang-Bo, Li, Hui-Hua, Li, and Yun-Long, Zhang
- Subjects
Male ,Mice, Inbred C57BL ,Mice ,Time Factors ,Proteome ,Physiology ,Angiotensin II ,Atrial Fibrillation ,Internal Medicine ,Animals ,Humans ,Citrate (si)-Synthase ,Cardiology and Cardiovascular Medicine - Abstract
Angiotensin (Ang) II and elevated blood pressure are considered to be the main risk factors for atrial fibrillation. However, the proteome profiles and key mediators/signaling pathways involved in the development of Ang II-induced atrial fibrillation remain unclear.Male wild-type C57BL/6 mice (10-week old) were infused with Ang II (2000 ng/kg per min) for 1, 2, or 3 weeks, respectively. Time series proteome profiling of atrial tissues was performed using isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry.We identified a total of 1566 differentially expressed proteins (DEPs) in the atrial tissues at weeks 1, 2, and 3 after Ang II infusion. These DEPs were predominantly involved in mitochondrial oxidation-reduction and tricarboxylic acid cycle in Ang II-infused atria. Moreover, coexpression network analysis revealed that citrate synthase, a rate-limiting enzyme in the tricarboxylic acid cycle, was localized at the center of the mitochondrial oxidation-reduction process, and its expression was significantly downreguated in Ang II-infused atria at different time points. Cardiomyocyte-specific overexpresion of citrate synthase markedly reduced atrial fibrillation susceptibility and atrial remodeling in mice. These beneficial effects were associated with increased ATP production and mitochondrial oxidative phosphorylation system complexes I-V expression and inhibition of oxidative stress.The current study defines the dynamic changes of the DEPs involved in Ang II-induced atrial fibrillation, and identifies that citrate synthase plays a protective role in regulating atrial fibrillation development, and increased citrate synthase expression may represent a potential therapeutic option for atrial fibrillation treatment.
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- 2022
28. MicroRNA-451a attenuates angiotensin II–induced cardiac fibrosis and inflammation by directly targeting T-box1
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Yun-Long Zhang, Xiao Han, Hao-Yuan Deng, Ze-Yin He, Hui-Hua Li, and Zhi-Chao Dong
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Cardiac function curve ,Physiology ,Cardiac fibrosis ,Inflammation ,Pharmacology ,Biochemistry ,Proinflammatory cytokine ,Mice ,Fibrosis ,medicine ,Animals ,Myocyte ,Myocytes, Cardiac ,business.industry ,Angiotensin II ,Myocardium ,General Medicine ,medicine.disease ,Mice, Inbred C57BL ,MicroRNAs ,cardiovascular system ,medicine.symptom ,business ,Myofibroblast - Abstract
Hypertension or angiotensin II (Ang II) induces cardiac inflammation and fibrosis, thus contributing to cardiac remodeling. MicroRNAs (miRNAs) are considered crucial regulators of cardiac homeostasis and remodeling in response to various types of stress. It has been reported that miR-451a is involved in regulating ischemic heart injury. However, its role in Ang II-induced cardiac fibrosis remains unknown. Cardiac remodeling was induced in mice by infusion of low-dose Ang II (490 ng/kg/min) with a minipump for 2 weeks. Echocardiography and histological examinations were performed to evaluate cardiac function and pathological changes. We observed that miR-451a expression was the most significantly downregulated in the hearts of Ang II-infused mice and in both primary cardiac myocytes and fibroblasts. Overexpression of miR-451a in mice significantly attenuated Ang II-induced cardiac fibrosis and inflammation. Conversely, knockdown of miR-451a in mice aggravated this effect. Bioinformatics analysis and a luciferase reporter assay revealed that TBX1 was a direct target of miR-451a. Mechanistically, miR-451a directly targeted TBX1 expression, which inhibited TGF-β1 production in both cardiac myocytes and fibroblasts, inactivating of TGF-β1/SMAD2/3 signaling, inhibiting myofibroblast differentiation and proinflammatory cytokine expression, and leading to attenuation of cardiac fibrosis and inflammation. In conclusion, these results indicate that miR-451a acts as a novel regulator of Ang II-induced cardiac fibrosis and inflammation by directly targeting TBX1, and may be a promising therapeutic target for treating hypertensive cardiac diseases.
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- 2021
29. Correction to: AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis
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Qiu-Yue Han, Nan Li, Lina Song, Cui Tian, Yu Liu, Hui-Hua Li, Yunlong Xia, Erhe Gao, Jie Du, and Hui Yang
- Subjects
Pharmacology ,Cancer Research ,medicine.medical_specialty ,Myocardial ischemia ,business.industry ,Myocardial apoptosis ,Angiogenesis ,Biochemistry (medical) ,Clinical Biochemistry ,Pharmaceutical Science ,Cell Biology ,medicine.disease ,Text mining ,Apoptosis ,Internal medicine ,medicine ,Cardiology ,business ,Reperfusion injury - Published
- 2021
30. S100a8/a9 contributes to sepsis-induced cardiomyopathy by activating ERK1/2-Drp1-mediated mitochondrial fission and respiratory dysfunction
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Feng Wu, Yan-Ting Zhang, Fei Teng, Hui-Hua Li, and Shu-Bin Guo
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Pharmacology ,Immunology ,Immunology and Allergy - Published
- 2023
31. Adipose Triglyceride Lipase Deficiency Aggravates Angiotensin II–Induced Atrial Fibrillation by Reducing Peroxisome Proliferator–Activated Receptor α Activation in Mice
- Author
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Xiao Han, Yun-Long Zhang, Yan-Xu Zhao, Shu-Bin Guo, Wen-Peng Yin, and Hui-Hua Li
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Cell Biology ,Molecular Biology ,Pathology and Forensic Medicine - Published
- 2023
32. Integrin CD11b Mediates Angiotensin Ii-Induced Hypertension and Vascular Injury by Regulating Macrophage Adhesion
- Author
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Qiu-Yue Lin, Jie Bai, Yun-Long Zhang, and Hui-Hua Li
- Published
- 2022
33. Blockage of Fibronectin 1 Ameliorates Myocardial Ischemia/Reperfusion Injury in Association with Activation of AMP-LKB1-AMPK Signaling Pathway
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Yun-Long Zhang, Pang-Bo Li, Xiao Han, Bo Zhang, and Hui-Hua Li
- Subjects
Inflammation ,Aging ,Article Subject ,Myocardial Infarction ,Myocardial Reperfusion Injury ,Cell Biology ,General Medicine ,AMP-Activated Protein Kinases ,Biochemistry ,Fibrosis ,Adenosine Monophosphate ,Fibronectins ,Mice ,Glucose ,Animals ,Signal Transduction - Abstract
Myocardial ischemia/reperfusion injury (I/RI) is closely associated with energy substrate metabolism. Fibronectin 1 (Fn1) was markedly elevated in the heart of I/R pigs and ischemic patients, but its role in myocardial I/RI is controversial and the precise mechanism involved remains elusive. Herein, we tested whether blockage of Fn1 with its inhibitor (fibronectin tetrapeptide, RGDS) would alleviate myocardial I/RI. Wild-type (WT) mice were administered with RGDS once 3 h before I/R operation and once at 24 or 48 h postreperfusion, and sacrificed at 24 or 72 h post-I/R, respectively. Cardiac function was evaluated by echocardiography. Myocardial infarction size, apoptosis, fibrosis, and inflammation were examined via histological staining. Uptake of glucose and fatty acids were detected by positron emission tomography (PET) and computer tomography (CT) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) and [18F]-fluoro-6-thia-heptadecanoic acid (FTHA), respectively. Our results showed that administration of RGDS to mice remarkably limited the I/R-induced myocardial infarct size, myocyte apoptosis, inflammation, oxidative stress, and fibrosis and improved cardiac contractile dysfunction. These protective effects were associated with upregulation of the AMP/ATP ratio and the activation of LKB1-AMPK signaling, which subsequently increased AS160-GLUT4-mediated glucose and fatty acid uptake, improved mitochondrial dynamic imbalance, and inactivated TGF-β and NF-κB signals in the I/R heart. In conclusion, the current study identified that blocking Fn1 protects against myocardial I/RI likely through activating the LKB1-AMPK-dependent signals and highlights that inhibition of Fn1 may be a novel therapeutic option for treating ischemic heart diseases.
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- 2022
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- View/download PDF
34. Development and Validation of an Immunoglobulin Glycosylation Risk Algorithm to Predict Mortality in Patients with Influenza Pneumonia
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Fei Teng, Jia-Hui Zhang, Xiao-Mei Zhang, Wen-Xin Liu, Hong-Ye Wang, Yu-Dan Cao, Hui-Hua Li, Xiaobo Yu, and Shu-Bin Guo
- Published
- 2022
35. Corrigendum to 'NADPH oxidase-derived H2O2 mediates the regulatory effects of microglia on astrogliosis in experimental models of Parkinson's disease' [Redox Biol. 2017, 12: 162–170]
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Fuqiang Sun, Cong Zhang, Xueying Zhou, Ke Wang, Qingshan Wang, Dan Zhang, Xiaofang Liu, Jau-Shyong Hong, Hui-Hua Li, Yuning Che, and Liyan Hou
- Subjects
Medicine (General) ,NADPH oxidase ,Parkinson's disease ,biology ,Microglia ,Chemistry ,QH301-705.5 ,Organic Chemistry ,Clinical Biochemistry ,medicine.disease ,Biochemistry ,Redox ,Astrogliosis ,Cell biology ,medicine.anatomical_structure ,R5-920 ,medicine ,biology.protein ,Biology (General) - Published
- 2021
36. The impact of preoperative glycated hemoglobin (HbA1c) on postoperative complications after elective major abdominal surgery: a meta-analysis
- Author
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Yuhe Ke, Ting Hway Wong, Yi Jing Ong, Hui Hua Li, Hairil Rizal Abdullah, and Joanna K. L. Wong
- Subjects
medicine.medical_specialty ,general surgery ,Population ,law.invention ,chemistry.chemical_compound ,operative surgical procedures ,Postoperative Complications ,Randomized controlled trial ,law ,Anesthesiology ,glycated hemoglobin a ,Abdomen ,Diabetes Mellitus ,Medicine ,Humans ,RD78.3-87.3 ,Risk factor ,Elective surgery ,education ,Glycated Hemoglobin ,education.field_of_study ,business.industry ,Surgery ,Anesthesiology and Pain Medicine ,chemistry ,Elective Surgical Procedures ,Meta-analysis ,Glycated hemoglobin ,Elective Surgical Procedure ,business ,Abdominal surgery - Abstract
Background: Diabetes is a risk factor for postoperative complications. Previous meta-analyses have shown that elevated glycated hemoglobin (HbA1c) levels are associated with postoperative complications in various surgical populations. However, this is the first meta-analysis to investigate the association between preoperative HbA1c levels and postoperative complications in patients undergoing elective major abdominal surgery.Methods: PRISMA guidelines were adhered to for this study. Six databases were searched up to April 1, 2020. Primary studies investigating the effect of HbA1c levels on postoperative complications after elective major abdominal surgery were included. Risk of bias and quality of evidence assessments were performed. Data were pooled using a random effects model. Meta-regression was performed to evaluate different HbA1c cut-off values. Results: Twelve observational studies (25,036 patients) were included. Most studies received a ‘good’ and ‘moderate quality’ score using the NOS and GRADE, respectively. Patients with a high HbA1c had a greater risk of anastomotic leaks (odds ratio [OR]: 2.80, 95% CI [1.63, 4.83], P < 0.001), wound infections (OR: 1.21, 95% CI [1.08, 1.36], P = 0.001), major complications defined as Clavien-Dindo [CD] 3–5 (OR: 2.16, 95% CI [1.54, 3.01], P < 0.001), and overall complications defined as CD 1–5 (OR: 2.12, 95% CI [1.48, 3.04], P < 0.001).Conclusions: An HbA1c between 6% and 7% is associated with higher risks of anastomotic leaks, wound infections, major complications, and overall postoperative complications. Therefore, guidelines with an HbA1c threshold > 7% may be putting pre-optimized patients at risk. Future randomized controlled trials are needed to explore causation before policy changes are made.
- Published
- 2021
37. Correction: Overexpression of Nrdp1 in the Heart Exacerbates Doxorubicin-Induced Cardiac Dysfunction in Mice
- Author
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Yuan Zhang, Yu-Ming Kang, Cui Tian, Yong Zeng, Li-Xin Jia, Xu Ma, Jie Du, and Hui-Hua Li
- Subjects
Multidisciplinary - Published
- 2022
38. Deficiency of peroxisome proliferator-activated receptor α attenuates apoptosis and promotes migration of vascular smooth muscle cells
- Author
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Ye Liu, Yong-Fen Qi, Aijuan Qu, Qingbo Xu, Dan Qi, Jie Du, Yanting Song, Frank J. Gonzalez, Yan Duan, Xia Wang, Shiyu Jiao, and Hui-Hua Li
- Subjects
Vascular smooth muscle ,QH301-705.5 ,Biophysics ,SM22α, smooth muscle 22α ,Peroxisome proliferator-activated receptor ,PPAR, peroxisome proliferator-activated receptor ,QD415-436 ,PPARα ,TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling ,Biochemistry ,VSMC, vascular smooth muscle cell ,PCR, polymerase chain reaction ,ERK, extracellular signal-regulated kinase ,Renin–angiotensin system ,Vascular remodeling ,Biology (General) ,Receptor ,chemistry.chemical_classification ,Ang II, angiotensin II ,TGF, tumor growth factor ,EC, endothelial cell ,Chemistry ,Angiotensin II ,MCP-1, monocyte chemoattractant protein-1 ,Peroxisome ,musculoskeletal system ,Pathophysiology ,ECM, extracellular matrix ,Cell biology ,Apoptosis ,Vascular smooth muscle cell ,cardiovascular system ,MAPK, mitogen-activated protein kinase ,Research Article - Abstract
Peroxisome proliferator-activated receptor (PPAR) α is widely expressed in the vasculature and has pleiotropic and lipid-lowering independent effects, but its role in the growth and function of vascular smooth muscle cells (VSMCs) during vascular pathophysiology is still unclear. Herein, VSMC-specific PPARα-deficient mice (PparaΔSMC) were generated by Cre-LoxP site-specific recombinase technology and VSMCs were isolated from mice aorta. PPARα deficiency attenuated VSMC apoptosis induced by angiotensin (Ang) II and hydrogen peroxide, and increased the migration of Ang II-challenged cells., Highlights • PPARα deficiency has both excitatory and inhibitory effects on VSMC function. • PPARα deficiency inhibits VSMC apoptosis but induces Ang II-induced migration. • The dual role of PPARα may lie behind the mixed clinical effects of fibrates.
- Published
- 2021
39. Long-Term Motor Cortical Electrical Stimulation Ameliorates 6-Hydroxydopamine-Induced Motor Dysfunctions and Exerts Neuroprotective Effects in a Rat Model of Parkinson’s Disease
- Author
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Chi-Wei Kuo, Ming-Yuan Chang, Ming-Yi Chou, Chien-Yuan Pan, Chih-Wei Peng, Hui-Chiun Tseng, Tsu-Yi Jen, Xiao-Kuo He, Hui-Hua Liu, Thi Xuan Dieu Nguyen, Pi-Kai Chang, and Tsung-Hsun Hsieh
- Subjects
cortical electrical stimulation ,Parkinson’s disease ,gait ,locomotor function ,neuroprotection ,6-OHDA ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
ObjectiveCortical electrical stimulation (CES) can modulate cortical excitability through a plasticity-like mechanism and is considered to have therapeutic potentials in Parkinson’s disease (PD). However, the precise therapeutic value of such approach for PD remains unclear. Accordingly, we adopted a PD rat model to determine the therapeutic effects of CES. The current study was thus designed to identify the therapeutic potential of CES in PD rats.MethodsA hemiparkinsonian rat model, in which lesions were induced using unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, was applied to identify the therapeutic effects of long-term (4-week) CES with intermittent theta-burst stimulation (iTBS) protocol (starting 24 h after PD lesion observation, 1 session/day, 5 days/week) on motor function and neuroprotection. After the CES intervention, detailed functional behavioral tests including gait analysis, akinesia, open-field locomotor activity, apomorphine-induced rotation as well as degeneration level of dopaminergic neurons were performed weekly up to postlesion week 4.ResultsAfter the CES treatment, we found that the 4-week CES intervention ameliorated the motor deficits in gait pattern, akinesia, locomotor activity, and apomorphine-induced rotation. Immunohistochemistry and tyrosine hydroxylase staining analysis demonstrated that the number of dopamine neurons was significantly greater in the CES intervention group than in the sham treatment group.ConclusionThis study suggests that early and long-term CES intervention could reduce the aggravation of motor dysfunction and exert neuroprotective effects in a rat model of PD. Further, this preclinical model of CES may increase the scope for the potential use of CES and serve as a link between animal and PD human studies to further identify the therapeutic mechanism of CES for PD or other neurological disorders.
- Published
- 2022
- Full Text
- View/download PDF
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