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1.
Medicine (Baltimore) ; 103(19): e37965, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728489

ABSTRACT

BACKGROUND: Heart failure is a common and severe condition, often complicated by diastolic dysfunction. Current standard therapies such as ACEIs and ARBs have limited efficacy in managing diastolic function. Sacubitril/Valsartan, an emerging therapy, warrants rigorous investigation to elucidate its impact on diastolic function in heart failure patients. METHODS: This systematic review and meta-analysis were conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and utilized the PICO schema. Searches were performed on 4 databases-PubMed, Embase, Web of Science, and Cochrane Library-without temporal restrictions. Inclusion and exclusion criteria were strictly defined, and quality assessments were conducted using the Cochrane Collaboration Risk of Bias tool. Both fixed-effects and random-effects models were used for statistical analysis, depending on inter-study heterogeneity assessed by I2 statistics and Chi-square tests. RESULTS: Out of 1129 identified publications, 8 studies met the criteria and were included in the meta-analysis. These studies consisted of both randomized controlled trials and cohort studies and featured diverse global populations. Significant reductions were found in the echocardiographic parameter E/e' ratio and LAVi upon treatment with Sacubitril/Valsartan compared to standard therapies, with mean differences of -1.38 and -4.62, respectively, both with P values < .01. CONCLUSIONS: This meta-analysis demonstrates that Sacubitril/Valsartan significantly improves diastolic function parameters in heart failure patients compared to standard treatments. These findings underscore the potential benefits of Sacubitril/Valsartan in the management of heart failure, particularly for patients with diastolic dysfunction.


Subject(s)
Aminobutyrates , Angiotensin Receptor Antagonists , Biphenyl Compounds , Drug Combinations , Heart Failure , Valsartan , Humans , Valsartan/therapeutic use , Aminobutyrates/therapeutic use , Biphenyl Compounds/therapeutic use , Heart Failure/drug therapy , Heart Failure/physiopathology , Angiotensin Receptor Antagonists/therapeutic use , Tetrazoles/therapeutic use , Diastole/drug effects
2.
J Adv Res ; 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38653371

ABSTRACT

INTRODUCTION: Myocardial ischemia-reperfusion (IR) injury is a common medical issue contributing to the onset and progression of ischemic heart diseases (IHD). Growth arrest-specific gene 6 (GAS6), a vitamin K-dependent secretory protein, promotes cell proliferation and inhibits inflammation and apoptosis through binding with Tyro3, Axl, and Mertk (TAM) receptors. OBJECTIVES: Our study aimed to examine the effect of GAS6 pathways activation as a potential new treatment in myocardial IR injury. METHODS: Gain- and loss-of-function experiments were utilized to determine the roles of GAS6 in the pathological processes of myocardial IR injury. RESULTS: Our results revealed down-regulated levels of GAS6, Axl, and SIRT1 in murine hearts subjected to IR injury, and cardiomyocytes challenged with hypoxia reoxygenation (HR) injury. GAS6 overexpression significantly improved cardiac dysfunction in mice subjected to myocardial IR injury, accompanied by reconciled mitochondrial dysfunction, oxidative stress, and apoptosis. In vitro experiments also observed a protective effect of GAS6 in cardiomyocytes. SIRT1 was found to function as a downstream regulator for GAS6/Axl signaling axis. Through screening a natural product library, a polyphenol natural compound catechin was identified to exhibit a protective effect by turning on GAS6/Axl-SIRT1 cascade. CONCLUSIONS: Together, our findings indicate that GAS6 emerges as a potential novel target in the management of myocardial IR injury and other related anomalies.

3.
J Agric Food Chem ; 72(18): 10640-10654, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38661066

ABSTRACT

Coronaviruses have consistently posed a major global concern in the field of livestock industry and public health. However, there is currently a lack of efficient drugs with broad-spectrum antiviral activity to address the challenges presented by emerging mutated strains or drug resistance. Additionally, the method for identifying multitarget drugs is also insufficient. Aminopeptidase N (APN) and 3C-like proteinase (3CLpro) represent promising targets for host-directed and virus-directed strategies, respectively, in the development of effective drugs against various coronaviruses. In this study, maduramycin ammonium demonstrated a broad-spectrum antiviral effect by targeting both of the proteins. The binding domains 4 Å from the ligand of both target proteins shared a structural similarity, suggesting that screening and designing drugs based on these domains might exhibit broad-spectrum and highly effective antiviral activity. Furthermore, it was identified that the polyether ionophores' ability to carry zinc ion might be one of the reasons why they were able to target APN and exhibit antiviral effect. The findings of this experiment provide novel perspectives for future drug screening and design, while also offering valuable references for the utilization of polyether ionophores in the management of livestock health.


Subject(s)
Antiviral Agents , CD13 Antigens , Ionophores , Livestock , Animals , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Ionophores/pharmacology , Ionophores/chemistry , CD13 Antigens/metabolism , CD13 Antigens/chemistry , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Coronavirus 3C Proteases/antagonists & inhibitors , Veterinary Drugs/pharmacology , Veterinary Drugs/chemistry , Coronavirus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyether Polyketides
4.
J Med Virol ; 96(3): e29512, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38483056

ABSTRACT

Coronaviruses (CoVs) have continuously posed a threat to human and animal health. However, existing antiviral drugs are still insufficient in overcoming the challenges caused by multiple strains of CoVs. And methods for developing multi-target drugs are limited in terms of exploring drug targets with similar functions or structures. In this study, four rounds of structural design and modification on salinomycin were performed for novel antiviral compounds. It was based on the strategy of similar topological structure binding properties of protein targets (STSBPT), resulting in the high-efficient synthesis of the optimal compound M1, which could bind to aminopeptidase N and 3C-like protease from hosts and viruses, respectively, and exhibit a broad-spectrum antiviral effect against severe acute respiratory syndrome CoV 2 pseudovirus, porcine epidemic diarrhea virus, transmissible gastroenteritis virus, feline infectious peritonitis virus and mouse hepatitis virus. Furthermore, the drug-binding domains of these proteins were found to be structurally similar based on the STSBPT strategy. The compounds screened and designed based on this region were expected to have broad-spectrum and strong antiviral activities. The STSBPT strategy is expected to be a fundamental tool in accelerating the discovery of multiple targets with similar effects and drugs.


Subject(s)
Coronavirus Infections , Coronavirus , Animals , Cats , Mice , Swine , Humans , Antiviral Agents/chemistry , Coronavirus Infections/drug therapy , Protease Inhibitors/pharmacology , Protease Inhibitors/chemistry
5.
BMC Cardiovasc Disord ; 24(1): 95, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331757

ABSTRACT

BACKGROUND: Red cell distribution width to albumin ratio (RAR) has been demonstrated to be associated with the risk of cardiovascular diseases. However, it is still unknown whether the RAR affects atrial fibrillation (AF). Therefore, this study aimed to investigate the association between RAR and AF in subjects hospitalized with coronary angiography. METHODS: A total of 2436 participants were retrospectively included. Red cell distribution width, albumin and other data were collected. AF was confirmed using 12-lead electrocardiogram (ECG) or 24-h Holter. All participants were divided into four groups according to the RAR values by quartile (Q1, Q2, Q3, Q4). Univariate and multivariate logistic regression were performed to examine the correlation between RAR and AF. RESULTS: Among the 2436 participants, 227 (9.3%) AF cases were observed. The RDW and RAR were significantly higher in AF group than in non-AF group (all P < 0.001). Univariate logistic regression showed an positive association between RAR and AF (P < 0.001). In multivariate logistic regression, RAR was found to be an independent risk factor of AF after adjusting for confounding factors (OR:2.015, 95%CI:1.315-3.089, P = 0.001). CONCLUSIONS: The present study indicated that elevated RAR level was independently correlated with increased risk of AF in subjects hospitalized with coronary angiography.


Subject(s)
Atrial Fibrillation , Erythrocyte Indices , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/etiology , Retrospective Studies , Coronary Angiography/adverse effects , Risk Factors
6.
Inflammation ; 46(6): 2416-2432, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37676465

ABSTRACT

Cardiac insufficiency is a common complication of sepsis with high mortality. Inflammatory programmed cell death (pyroptosis) executed by NLRP3/gasdermin D (GSDMD) is intrinsically correlated with septic myocardial injury. However, it remains unclear whether PIK3CG, a classical target of septic myocardial injury, can affect pyroptosis by regulating NLRP3/GSDMD signaling. In this study, a series of experimental methods were used to observe the effect of PIK3CG on NLRP3/GSDMD-mediated pyroptosis in Cecal ligation and puncture (CLP)-injured BALB/c mice and lipopolysaccharide (LPS)-injured HL-1 cardiomyocytes. Transcriptome analysis of CLP-injured myocardium revealed a regulatory relationship between PIK3CG and NLRP3/GSDMD signaling, which was further verified in clinical myocardium samples from GEO database. Both in vitro and in vivo experiments showed that the protein and mRNA levels of PIK3CG, GSDMD, NLRP3, IL-1ß, Caspase-1, and IL-18 were significantly increased. Importantly, PIK3CG siRNA was found to improve these changes, while PIK3CG overexpression worsened them. Notably, pyroptosis induced by CLP in the myocardium was reversed by the PIK3CG inhibitor (AS-604850). In conclusion, PIK3CG activates NLRP3 inflammasomes, thus promoting pyroptosis in septic myocardial injury.


Subject(s)
NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Animals , Mice , Caspase 1/metabolism , Inflammasomes/metabolism , Myocytes, Cardiac/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Signal Transduction
7.
BMC Geriatr ; 23(1): 348, 2023 06 03.
Article in English | MEDLINE | ID: mdl-37270473

ABSTRACT

BACKGROUND: Distal transradial access (dTRA) has been suggested to have great advantages over cTRA. However, there is a lack of preliminary data on dTRA in patients undergoing emergency coronary angiography (CAG) or percutaneous coronary intervention (PCI). To explore the feasibility and safety of distal transradial access in patients with acute chest pain. METHODS: A total of 1269 patients complaining of acute chest pain in our emergency department from January 2020 to February 2022 were retrospectively included. The patients who met the inclusion criteria were divided into the conventional transradial access (cTRA) group (n = 238) and the dTRA group (n = 158). Propensity score matching was used to minimize the baseline differences. RESULTS: The cannulation success rate in the dTRA group was significantly lower than that in the cTRA group (87.41% vs. 94.81%, p < 0.05). No significant differences in the puncture time and total procedure time were noted between the two groups (p > 0.05). Compared with the cTRA group, the hemostasis duration was significantly shorter [4(4, 4) h vs. 10(8, 10) h, p < 0.001) and the incidence of minor bleeding (BARC Type I and II) was significantly lower in the dTRA group than that in the cTRA group (0.85% vs. 5.48%, p = 0.045). Asymptomatic radial artery occlusion was observed in six patients (5.83%) in the cTRA group and one patient (1.14%) in the dTRA group (p = 0.126). The subgroup analysis of ST-elevation myocardial infarction (STEMI) showed no significant differences in the puncture time, D-to-B time or total procedure time between the two groups. CONCLUSIONS: The dTRA for emergency CAG or PCI has an acceptable success rate and puncture time, a shorter hemostasis time, and a downward trend in RAO rate compared to the cTRA. The dTRA did not increase the D-to-B time in emergency coronary interventions in STEMI patients. On the contrary, a low incidence of RAO by the dTRA created an opportunity for future coronary interventions in non-culprit vessels in the same access. TRIAL REGISTRATION: Retrospectively registered in Chinese Clinical Trial Registry (registry number: ChiCTR2200061104, date of registration: June 15, 2022).


Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Cohort Studies , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Propensity Score , Feasibility Studies , Chest Pain/diagnostic imaging , Chest Pain/epidemiology , Radial Artery/diagnostic imaging , Radial Artery/surgery , Treatment Outcome
8.
Ageing Res Rev ; 88: 101963, 2023 07.
Article in English | MEDLINE | ID: mdl-37245633

ABSTRACT

Ageing is a physiological/pathological process accompanied by the progressive damage of cell function, triggering various ageing-related disorders. Phosphatidylinositol 3-kinase (PI3K), which serves as one of the central regulators of ageing, is closely associated with cellular characteristics or molecular features, such as genome instability, telomere erosion, epigenetic alterations, and mitochondrial dysfunction. In this review, the PI3K signalling pathway was firstly thoroughly explained. The link between ageing pathogenesis and the PI3K signalling pathway was then summarized. Finally, the key regulatory roles of PI3K in ageing-related illnesses were investigated and stressed. In summary, we revealed that drug development and clinical application targeting PI3K is one of the focal points for delaying ageing and treating ageing-related diseases in the future.


Subject(s)
Aging , Phosphatidylinositol 3-Kinase , Phosphatidylinositol 3-Kinase/metabolism , Humans , Animals , Signal Transduction , Aging/pathology , Aging/physiology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Metabolic Diseases/metabolism , Metabolic Diseases/pathology , Heart Diseases/metabolism , Heart Diseases/pathology , Neoplasms/metabolism , Neoplasms/pathology
9.
J Sep Sci ; 46(13): e2300003, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37078121

ABSTRACT

Fatty acids have multitudinous biological functions and play a crucial role in many biological processes, but due to poor ionization efficiency and lack of appropriate internal standards, the comprehensive quantification of fatty acids by liquid chromatography-tandem mass spectrometry is still challenging. In this study, a new, accurate, and reliable method for quantifying 30 fatty acids in serum using dual derivatization was proposed. Indole-3-acetic acid hydrazide derivants of fatty acids were used as the internal standard and indole-3-carboxylic acid hydrazide derivants of them were used to quantify. The derivatization conditions were systematically optimized and the method validation results showed good linearity with R2  > 0.9942, low detection limit (0.03-0.6 nM), precision (1.6%-9.8% for intra-day and 4.6%-14.1% for inter-day), recovery (88.2%-107.2% with relative standard deviation < 10.5%), matrix effect (88.3%-105.2% with the relative standard deviation < 9.9%) and stability (3.4%-13.8% for fatty acids derivants in 24 h at 4°C and 4.2%-13.8% for three freeze-thaw cycles). Finally, this method was successfully applied to quantify fatty acids in serum samples of Alzheimer's patients. In contrast to the healthy control group, nine fatty acids showed a significant increase in the Alzheimer's disease group.


Subject(s)
Fatty Acids , Tandem Mass Spectrometry , Humans , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid , Hydrazines
10.
Free Radic Biol Med ; 204: 8-19, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37085126

ABSTRACT

Sepsis can cause various organ dysfunction, which heart failure may be associated with significant mortality. Recently, natural plant extracts have gradually attracted people's attention in the clinical treatment of cardiovascular diseases. Psoralidin (PSO) is one of the main bioactive compounds from the seeds of Psoralea corylifolia L and exhibits remarkable protective effects in diseases, including cancer, osteoporosis, and depression. Recently, NR1H3 is one of the emerging nuclear receptors targets for the various drugs. This study first reported the porotective role of PSO in septic myocardial injury, which was mainly attributed to the NR1H3-dependent manner. NR1H3 knockout mice subjected to cecal ligation and puncture (CLP) were used to investigate the involvement of NR1H3 in PSO protection. Our results showed that PSO prominently improved cardiac function, attenuated inflammation, inhibited oxidative stress, improved mitochondrial function, regulated ERS, suppressed apoptosis, and particularly increased NR1H3 and p-AMPK levels. However, NR1H3 knockout reversed the positive role of PSO in septic mice. Furthermore, activation of NR1H3 by T0901317 also increased the activity of AMPK and ACC in the HL-1 cardiomyocytes, indicating the regulatory relationship between NR1H3 and AMPK signaling. Together, this study demonstrated the beneficial effect of PSO in septic myocardial injury through activation of NR1H3/AMPK pathway.


Subject(s)
Heart Injuries , Sepsis , Mice , Animals , AMP-Activated Protein Kinases/metabolism , Myocardium/metabolism , Signal Transduction , Mice, Knockout , Sepsis/drug therapy , Sepsis/genetics , Sepsis/complications
11.
Invest. clín ; 63(4): 388-399, dic. 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1534673

ABSTRACT

Abstract Although ABO blood groups have been associated with cardiovascular disease, little is known about whether ABO blood groups contribute to the risk of the presence and severity of coronary artery disease (CAD) in elderly individuals with hypertension. This study was aimed to explore this association. A total of 793 hypertensive patients aged ≥60 years out of 2095 patients who underwent primary coronary angiography were retrospectively included. They were divided into CAD and non-CAD groups. Demographic and clinical characteristics, ABO blood groups and other biochemical parameters were compared. Further evaluation was performed to determine the impact of ABO blood groups on CAD severity using the Gensini score and the number of significantly diseased vessels. A logistic regression model was constructed to identify the association of ABO blood groups with CAD. There was a substantial difference in the distribution of ABO blood groups in elderly and hypertensive adults with and without CAD (p=0.022). Hypertensive patients with CAD had a significantly lower proportion of the blood group B than those without CAD (p=0.008). Compared to those with non-Blood group B, hypertensive elderly with a blood group B tended to have significantly lower concentrations of TC, LDL -C and Apo B, and a lower number of significantly stenosed vessels. The blood group B was found to be an independent protective factor for CAD in elderly with hypertension. The blood group B is significantly associated with a decreased risk of CAD and is inversely correlated with the severity of coronary stenosis in the elderly with hypertension.


Resumen Aunque los tipos de sangre ABO están asociados con enfermedades cardiovasculares, se sabe poco sobre si los tipos de sangre ABO estás relacionados con la presencia y gravedad de la enfermedad arterial coronaria (CAD) en pacientes de edad avanzada con hipertensión. El objetivo de este estudio fue explorar esta relación. Se incluyeron retrospectivamente un total de 793 pacientes hipertensos de ≥60 años tomados de un grupo de 2095 pacientes sometidos a angiografía coronaria primaria. Se dividieron en el grupo de cardiopatía coronaria (CAD) y el grupo sin cardiopatía coronaria (no-CAD). Se compararon las características demográficas y clínicas, el grupo sanguíneo ABO y otros parámetros bioquímicos. El efecto del grupo sanguíneo ABO sobre la gravedad de la CAD se evaluó con la puntuación Gensini y el número de vasos sanguíneos patológicos significativos. Se construyó un modelo de regresión logística para determinar la relación entre el grupo sanguíneo ABO y la CAD. Hubo una diferencia significativa en la distribución de los grupos sanguíneos ABO entre los ancianos con y sin cardiopatía coronaria y los adultos con hipertensión (P=0,022). La proporción del grupo sanguíneo B en pacientes hipertensos con cardiopatía coronaria fue significativamente menor que en pacientes sin cardiopatía coronaria (P=0,008). En comparación con los grupos sanguíneos no B, las concentraciones de TC, LDL - C y Apolipoproteína B en los ancianos hipertensos del Grupo B fueron significativamente menores, y el número de estenosis vascular fue significativamente menor. El Grupo B es un factor protector independiente de la CAD en pacientes de edad avanzada con hipertensión. El Grupo B se correlacionó significativamente con la reducción del riesgo de cardiopatía coronaria y negativamente con la gravedad de la estenosis coronaria en pacientes de edad avanzada con hipertensión.

12.
J Interv Cardiol ; 2022: 1901139, 2022.
Article in English | MEDLINE | ID: mdl-36082307

ABSTRACT

The study aimed to investigate the efficacy and safety of coronary intervention via distal transradial access (dTRA) in patients with low body mass index (BMI). A total of 67 patients with low BMI who underwent coronary intervention, comprising 29 patients via dTRA and 38 patients via conventional transradial access (cTRA), were retrospectively included. There was no significant difference in the puncture success rate between the two groups (dTRA 96.6%, cTRA 97.4%, P=0.846). Compared with the cTRA group, the success rate of one-needle puncture in the dTRA group was lower (51.7% vs. 81.6%, P=0.020). The compression haemostasis time in the dTRA group was shorter than that in the cTRA group (P < 0.001). However, the incidence of radial artery occlusion was lower in the dTRA group than in the cTRA group (4.0% vs. 33.3%, P=0.007). In conclusion, coronary intervention via dTRA was safe and effective in patients with low BMI.


Subject(s)
Body Mass Index , Percutaneous Coronary Intervention , Arterial Occlusive Diseases/epidemiology , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Punctures , Radial Artery , Retrospective Studies
13.
Int Immunopharmacol ; 107: 108681, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35278832

ABSTRACT

Myocardial ischemia reperfusion (I/R) injury is an important complication of myocardial infarction reperfusion therapy, and no effective treatment has been identified. Based on preexisting evidence, C1q/tumor necrosis factor-related protein 3 (CTRP3) has been reported to be closely associated with myocardial dysfunction. In this study, we found that CTRP3 was downregulated in acute coronary syndrome (ACS) patients and myocardial I/R mice. Silence of CTRP3 aggravated cardiac systolic function due to I/R of mice, while CTRP3 overexpression ameliorated cardiac function. Moreover, overexpression of CTRP3 improved I/R inhibitory effects on the levels of creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and cardiac troponin-I (cTn-I), myocardial infarction area, the intensity of the 3-nitrotyrosine (3-NT), apoptosis and protein levels of LAMP1, JNK-Interacting Protein-2 (JIP-2) and JNK, while these effects could be exacerbated by downregulation of CTRP3. Co-IP experiments could identify physical interactions between CTRP3 and lysosomal-associated membrane protein 1 (LAMP1) and Numb and JIP2. LAMP1 silence aggravated the inhibition effects of I/R on JIP2 and JNK protein expression, CPK, LDH and cTn-I levels and caspase-3 activity, while overexpression of LAMP1 recovered these inhibition effects of I/R. JNK inhibitor (SP600125) could reverse the inhibitory effects of CTRP3 overexpression on CPK, LDH, cTn-I, myocardial infarction, strong positive staining for 3-NT and apoptosis. These findings demonstrated that CTRP3 protected against injury caused by myocardial I/R through activating LAMP1/JIP2/JNK pathway to attenuate myocardial injury, improve left ventricular function, decrease myocardial infarction, and reduce myocardial apoptosis.


Subject(s)
Myocardial Infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Adipokines , Animals , Apoptosis , Humans , Lysosomal-Associated Membrane Protein 1 , Lysosomal Membrane Proteins/metabolism , MAP Kinase Signaling System/physiology , Mice , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/metabolism , Myocardium/pathology , Transcription Factors/metabolism , Tumor Necrosis Factors
14.
Environ Toxicol ; 37(7): 1629-1641, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35258167

ABSTRACT

Cardiomyocyte dysfunction and apoptosis induced by ischemia-hypoxia are common features of many acute and chronic heart diseases. WW domain-containing E3 ubiquitin ligase (WWP2) has been identified as an important regulator in pathogenesis of some health-threatening diseases. Although a couple of recent reports prompted the potential role of WWP2 in heart dysfunction, however, its exact role and how its expression was regulated in ischemic-hypoxic cardiomyocytes are still elusive. Here, we found that WWP2 protein level was induced in anoxia/reoxygenation (A/R) treated cardiomyocytes in a time-dependent manner, accompanied by synchronous expression of LINC01588 and HNRNPL. Knockdown of LINC01588 increased cardiomyocyte apoptosis, the level of oxidative stress, and expression of pro-inflammatory cytokine genes, down-regulated the expression of WWP2 and promoted expression of SEPT4 gene that contributed to cardiomyocyte dysfunction and was a target gene of WWP2. LINC01588 overexpression improved the functions of A/R treated cardiomyocytes, up-regulated WWP2 and reduced SEPT4 expression. In the mechanism exploration, we found that LINC01588 could directly bind with HNRNPL protein that could interact with WWP2, suggesting that WWP2 was involved in the regulation of LINC01588 in A/R treated cardiomyocytes. Moreover, WWP2 inhibition declined the protective role of LINC01588 in cardiomyocyte dysfunction induced by A/R. Finally, we demonstrated that LINC01588 overexpression improved acute myocardial infarction in mice in vivo. In conclusion, LINC01588 improved A/R-induced cardiomyocyte dysfunction by interacting with HNRNPL and promoting WWP2-mediated degradation of SEPT4.


Subject(s)
Myocytes, Cardiac , RNA, Long Noncoding , Ribonucleoproteins , Ubiquitin-Protein Ligases , Animals , Apoptosis/physiology , Cell Hypoxia , Mice , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Ribonucleoproteins/genetics , Ribonucleoproteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
15.
Aging (Albany NY) ; 14(3): 1321-1335, 2022 02 03.
Article in English | MEDLINE | ID: mdl-35114641

ABSTRACT

BACKGROUND: C1q/tumor necrosis factor-related protein 3 (CTRP3) has been reported to be a crucial regulator in myocardial infarction. Nevertheless, the potential molecular mechanism of CTRP3 in ischemia/reperfusion (I/R) injury remains largely unclear. METHODS: The cell model of myocardial I/R injury was established by oxygen-glucose deprivation/reoxygenation (OGD/R) of rat cardiomyocyte H9C2. Expression of CTRP3 and lysosomal-associated membrane protein 1 (LAMP1) was detected in H9C2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R). H9C2 cells were transfected with overexpression plasmids of CTRP3 (pcDNA-CTRP3) and LAMP1 (pcDNA-LAMP1), or CTRP3 small interfering RNA (si-CTRP3) or/and pcDNA-LAMP1, and cell proliferation, apoptosis and oxidative stress were testified. Co-IP assay was performed to validate the relationship among CTRP3, LAMP1 and JIP2. The role of CTRP3 and LAMP1 in JIP2/JNK pathway was evaluated with Western blot assay. Furthermore, in vivo myocardial I/R injury model was constructed to investigate the effect of CTRP3. RESULTS: Overexpression of CTRP3 and LAMP1 both significantly promoted cell proliferation, inhibited apoptosis and the production of reactive oxygen species (ROS), malondialdehyde (MAD) and cardiac troponin (cTn-I), while silencing CTRP3 exerted the opposite effects, and LAMP1 overexpression reversed the effect of silencing CTRP3 on the aspects above. CTRP3 interacted with LAMP1, and both CTRP3 and LAMP1 bound with JIP2. SP600125 (JNK inhibitor) could restore the effects of CTRP3 or LAMP1 overexpression on the expression of JIP2 and phosphorylated-JNK (p-JNK), proliferation and apoptosis. Moreover, overexpression of CTRP3 improved cardiac I/R injury in vivo. CONCLUSION: CTRP3 alleviates cardiac I/R injury by elevating LAMP1 and activating JIP2/JNK signaling pathway, which may serve as a potential therapeutic target for I/R injury.


Subject(s)
Myocardial Infarction , Myocardial Reperfusion Injury , Animals , Apoptosis , Glucose/metabolism , Lysosomal-Associated Membrane Protein 1/metabolism , MAP Kinase Signaling System , Myocardial Infarction/metabolism , Myocardial Reperfusion Injury/metabolism , Myocytes, Cardiac/metabolism , Oxygen/metabolism , Rats , Signal Transduction
16.
J Endovasc Ther ; 29(5): 755-762, 2022 10.
Article in English | MEDLINE | ID: mdl-35001676

ABSTRACT

PURPOSE: Radial artery occlusion (RAO) is one of the common complications after coronary intervention via the conventional radial artery approach. The purpose of the study was to explore the safety and feasibility of retrograde recanalization of the occluded radial artery via a distal radial artery (DRA) approach. METHODS: Combined with the practice of our centre and a literature review, we summarized the procedure of retrograde recanalization of RAO, success rate, and complications. RESULTS: A total of 14 of 15 patients with 15 pieces of occluded radial arteries were successfully recanalized via the DRA in our centre. In the 15 occluded vessels, 11 vessels (73.3%) had total occlusion and 4 vessels (26.7%) had functional occlusion. Four of 15 occluded vessels were acute occlusions. Two acute RAOs were only treated with aspiration via sheath, 11 RAOs with balloon angioplasty, and 2 RAOs with both, respectively. In 6 patients, cardiac catheterization was carried out via the DRA after recanalizing the RAO. A total of 10 studies reporting the results of recanalization of RAO via the DRA were systematically retrieved in the present study. In 3 case series, the number of cases was more than 5, and the success rate of recanalization was more than 85.7%. Two studies reported complications, including dissection in one case, hematoma in 2 cases, and pain in the forearm during angioplasty. CONCLUSIONS: Recanalization of the occluded radial artery via the DRA was safe and effective. When repeat cardiac catheterization was required, recanalization of the RAO and subsequent coronary angiography or intervention through the ipsilateral radial artery approach was feasible.


Subject(s)
Arterial Occlusive Diseases , Radial Artery , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/therapy , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Coronary Angiography/adverse effects , Coronary Angiography/methods , Humans , Radial Artery/diagnostic imaging , Treatment Outcome
17.
Exp Ther Med ; 22(3): 930, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34306199

ABSTRACT

MicroRNAs (miR) are a group of non-coding, small RNAs, 18-20 nucleotides in length, that are frequently involved in the development of a variety of different types of cancer, including glioma, which is a type of severe tumor in the brain. Previous studies reported that miR-124 levels were downregulated in glioma specimens; however, the potential role of miR-124 in glioma currently remains unclear. The present study performed experiments, including dual-luciferase reporter assay (DLRA), MTT assay, transwell assay and flow cytometry, with the aim of elucidating the molecular mechanism of miR-124 in glioma. The results indicated that miR-124 expression was decreased in glioma tissues, accompanied by the increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN). The expression of EMMPRIN was inhibited by miR-124 transfection. The DLRA results revealed that EMMPRIN directly targets miR-124. Furthermore, upon overexpression of miR-124 in the U87 cells, cell proliferation was significantly inhibited, apoptosis was increased, and cell migration and invasion were decreased. Furthermore, tumor growth was blocked by miR-124 in mice. Based on these results, the present study concluded that miR-124 is critical for amelioration of glioma by targeting EMMPRIN, thereby acting as a tumor suppressor. Thus, miR-124/EMMPRIN constitutes a plausible basis for the treatment of glioma.

18.
J Cell Physiol ; 236(7): 4807-4828, 2021 07.
Article in English | MEDLINE | ID: mdl-33305467

ABSTRACT

Liver X receptor α (LXRα; also known as NR1H3), an isoform of LXRs, is a member of the nuclear receptor family of transcription factors and plays essential roles in the transcriptional control of cholesterol homeostasis. Previous in-depth phenotypic analyses of mouse models with deficient LXRα have also demonstrated various physiological functions of this receptor within inflammatory responses. LXRα activation exerts a combination of metabolic and anti-inflammatory actions resulting in the modulation and the amelioration of inflammatory disorders. The tight "repercussions" between LXRα and inflammation, as well as cholesterol homeostasis, have suggested that LXRα could be pharmacologically targeted in pathologies such as atherosclerosis, acute lung injury, and Alzheimer's disease. This review gives an overview of the recent advances in understanding the roles of LXRα in inflammation and inflammation-associated diseases, which will help in the design of future experimental researches on the potential of LXRα and advance the investigation of LXRα as pharmacological inflammatory targets.


Subject(s)
Cholesterol/metabolism , Inflammation/pathology , Lipid Metabolism/physiology , Liver X Receptors/metabolism , Acute Lung Injury/pathology , Alzheimer Disease/pathology , Animals , Atherosclerosis/pathology , Humans , Liver X Receptors/genetics , Mice , Protein Isoforms/genetics , Protein Isoforms/metabolism
19.
Eur J Pharmacol ; 872: 172977, 2020 Apr 05.
Article in English | MEDLINE | ID: mdl-32007500

ABSTRACT

Exosomes are membrane-derived vesicles and play a critical role in cell signaling by transferring RNAs and proteins to target cells through fusion with the cell membrane. Long non-coding RNA-small nucleolar RNA host gene 9 (lncRNA-SNHG9) was proven to be an important element in lncRNA-mRNA interaction networks during adipocyte differentiation, suggesting its potential involvement in the development of obesity, an important risk factor of cardiovascular and cerebrovascular endothelial dysfunction. However, the role of lncRNA-SNHG9 within the exosome in endothelial dysfunction of obese patients is largely unknown. In this study, we proved that adipocytes-derived exosomal SNHG9 were downregulated in obese persons and further decreased in obese individuals with endothelial dysfunction. Functional experimentations demonstrated that adipocytes-derived exosomal SNHG9 alleviated inflammation and apoptosis in endothelial cells. Bioinformatic analysis revealed that there was a potential interaction between SNHG9 and the TNF receptor type 1-associated death domain protein (TRADD) mRNA. Then, RNA-binding protein immunoprecipitation assay based on Ago2 antibody and ribonuclease protection assay demonstrated that exosomal SNHG9 directly bound to a specific region in TRADD mRNA sequence and formed an RNA dimeric inducible silencing complex. Moreover, knockdown of TRADD markedly inhibited inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs), whereas overexpression of TRADD dramatically neutralized the protective effect of exosomal SNHG9 on epithelial dysfunction. Therefore, SNHG9 could prevent endothelial dysfunction in obese patients by suppressing inflammation and apoptosis, indicating that SNHG9 may be a potential therapeutic target for obese patients with endothelial dysfunction.


Subject(s)
Cardiovascular Diseases/pathology , Exosomes/metabolism , Obesity/complications , RNA, Long Noncoding/metabolism , TNF Receptor-Associated Death Domain Protein/genetics , Adipocytes/cytology , Adipose Tissue/cytology , Adolescent , Apoptosis/genetics , Apoptosis/immunology , Cardiovascular Diseases/blood , Cardiovascular Diseases/immunology , Cell Line , Child , Computational Biology , Down-Regulation , Endothelium, Vascular/cytology , Endothelium, Vascular/immunology , Endothelium, Vascular/pathology , Gene Knockdown Techniques , Human Umbilical Vein Endothelial Cells , Humans , Mesenchymal Stem Cells , Obesity/blood , Obesity/immunology , Obesity/pathology , RNA, Long Noncoding/blood , RNA, Long Noncoding/isolation & purification , TNF Receptor-Associated Death Domain Protein/metabolism
20.
J Craniofac Surg ; 30(1): 141-144, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30616310

ABSTRACT

OBJECTIVE: The aim of this study is to investigate the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone-implant osteointegration in osteoporotic rats. MATERIALS AND METHODS: Thirty-six female Wistar rats were randomly divided into 3 groups: sham-operation (SHAM), ovariectomized (OVX), and ovariectomized with rhBMP-2 (OVX + rhBMP-2). The bone density of right tibia was observed with x-ray and the serum alkaline phosphatase (ALP) activity was measured preovariectomy and postovariectomy using an ALP-kit. In OVX + rhBMP-2 group, rhBMP-2 was embedded in the peri-implant area, while SHAM and OVX groups did not contain rhBMP-2. Four and eight weeks after implantation, the rats were killed and the right tibia with implants was taken by x-ray. Histologic changes were investigated by hematoxylin and eosin staining, scanning electron microscope (SEM), and energy dispersive spectrometer examinations. RESULTS: The serum ALP level was significantly higher in ovariectomized rats compared with that before ovariectomy (P < 0.05), while no difference was found in SHAM rats. At 12 weeks after ovariectomy, radiographic and histologic findings showed significant osteoporotic changes in proximal tibial metaphyses of OVX rats, including reduced cortical bone density and enlargement of bone marrow cavity compared with SHAM ones. The results of implantation verified new bone formation around implants in OVX + rhBMP-2 and SHAM groups, indicating favorable bone healing and osseointegration. No bone resorption was found in OVX + rhBMP-2 group, while some soft tissue was observed in bone-implant interface in SHAM group. In OVX group, there was no effective bone-implant osseointegration and mature bone formed around implants, and some implants were even lost due to chronic inflammation. The percentage of calcium and phosphorous atoms was significantly higher and the percentage of sulfur element was significantly lower in peri-implant area in OVX + rhBMP-2 and SHAM groups than that in OVX group. CONCLUSION: rhBMP-2 could enhance the osseous healing and restore bone-implant osseointegration in osteoporotic rats.


Subject(s)
Bone Morphogenetic Protein 2/therapeutic use , Bone-Implant Interface/pathology , Osseointegration/drug effects , Osteoporosis/complications , Ovariectomy , Tibia/surgery , Transforming Growth Factor beta/therapeutic use , Animals , Bone Density/physiology , Bone Density Conservation Agents , Bone-Anchored Prosthesis , Disease Models, Animal , Female , Osteoporosis/pathology , Rats , Rats, Wistar , Recombinant Proteins/therapeutic use , Tibia/pathology , Titanium/pharmacology
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