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BACKGROUND: Endothelial cells (ECs) can confer neuroprotection by secreting molecules. This study aimed to investigate whether DNA methylation contributes to the neuroprotective gene expression induced by hypoxia preconditioning (HPC) in ECs and to clarify that the secretion of molecules from HPC ECs may be one of the molecular mechanisms of neuroprotection. METHODS: Human microvascular endothelial cell-1 (HMEC-1) was cultured under normal conditions (C), hypoxia(H), and hypoxia preconditioning (HPC), followed by the isolation of culture medium (CM). SY5Y cell incubated with the isolated CM from HMEC-1 was exposed to oxygen-glucose deprivation (OGD). The DNA methyltransferases (DNMTs), global methylation level, miR-126 and its promotor DNA methylation level in HMEC-1 were measured. The cell viability and cell injury in SY5Y were detected. RESULTS: HPC decreased DNMTs level and global methylation level as well as increased miR-126 expression in HMEC-1. CM from HPC treated HMEC-1 also relieved SY5Y cell damage, while CM from HMEC-1 which over-expression of miR-126 can reduce injury in SY5Y under OGD condition. CONCLUSIONS: These findings indicate EC may secrete molecules, such as miR-126, to execute neuroprotection induced by HPC through regulating the expression of DNMTs.
Subject(s)
Cell Hypoxia , DNA Methylation , Endothelial Cells , MicroRNAs , Neurons , MicroRNAs/genetics , MicroRNAs/metabolism , DNA Methylation/genetics , Humans , Endothelial Cells/metabolism , Cell Hypoxia/genetics , Neurons/metabolism , Up-Regulation/genetics , Cell Survival/genetics , Glucose/metabolism , Cell Line , Oxygen/metabolism , Promoter Regions, Genetic/geneticsABSTRACT
Wang L, Fu G, Han R, Fan P, Yang J, Gong K, Zhao Z, Zhang C, Sun K, Shao GMALAT1 and NEAT1 Are Neuroprotective during Hypoxic Preconditioning in the Mouse Hippocampus Possibly by Regulation of NR2B High Alt Med Biol. 00:000-000, 2024. Background: The regulation of noncoding ribonucleic acid (ncRNA) has been shown to be involved in cellular and molecular responses to hypoxic preconditioning (HPC), a situation created by the induction of sublethal hypoxia in the brain. The ncRNAs metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and nuclear paraspeckle assembly transcript 1 (NEAT1) are abundantly expressed in the brain, where they regulate the expression of various genes in nerve cells. However, the exact roles of MALAT1 and NEAT1 in HPC are not fully understood. Methods: A mouse model of acute repeated hypoxia was used as a model of HPC, and MALAT1 and NEAT1 levels in the hippocampus were measured using real-time polymerase chain reaction (PCR). The mRNA and protein levels of N-methyl-d-aspartate receptor subunit 2 B (NR2B) in the mouse hippocampus were measured using real-time PCR and western blotting, respectively. HT22 cells knocked-down for MALAT1 and NEAT1 were used for in vitro testing. Expression of NR2B, which is involved in nerve cell injury under ischemic and hypoxic conditions, was also evaluated. The levels of spectrin and cleaved caspase-3 in MALAT1 and NEAT1 knockdown HT22 cells under oxygen glucose deprivation/reperfusion (OGD/R) were determined by western blotting. Results: HPC increased the expression of MALAT1 and NEAT1 and decreased the expression of NR2B mRNA in the mouse hippocampus (p < 0.05). Knockdown of MALAT1 and NEAT1 increased both NR2B mRNA and protein levels nearly twofold and caused damage under OGD/R conditions in HT22 cells (p < 0.05). Conclusion: MALAT1 and NEAT1 exert neuroprotective effects by influencing the expression of NR2B.
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Based on the social exchange theory and conservation of resources theory, the present research aimed to study the role of reciprocity beliefs in the relationship between workplace ostracism and knowledge hiding among college teachers. The study was conducted on a sample of 490 college teachers (i.e., 250 men & 240 women). The sample's age ranged from 24 to 58 years (M = 28, SD = 1.30). Psychometrically strong measurement tools were used to measure the constructs. Simple linear regression analysis demonstrated workplace ostracism as a significant positive predictor of knowledge hiding for college teachers. Mediation analysis demonstrated that negative and generalized reciprocity beliefs significantly mediated the relationship between workplace ostracism and knowledge hiding. This research will help organizations develop clear policies that encourage knowledge sharing and provide support systems for instructors with experience of ostracism. Limitations and suggestions of the current study for further empirical endeavors have also been discussed.
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BACKGROUND: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. METHODS: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. RESULTS: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. CONCLUSIONS: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.
Subject(s)
Biomarkers , Exosomes , Myocardial Infarction , RNA, Circular , Humans , RNA, Circular/genetics , RNA, Circular/blood , Exosomes/genetics , Exosomes/metabolism , Myocardial Infarction/genetics , Myocardial Infarction/blood , Myocardial Infarction/diagnosis , Biomarkers/blood , Male , Middle Aged , Female , Aged , High-Throughput Nucleotide Sequencing , Real-Time Polymerase Chain Reaction , Case-Control StudiesABSTRACT
RATIONALE: Phacolytic glaucoma (PLG), a secondary open-angle glaucoma caused by high molecular weight proteins leaking through the capsule of a hypermature cataract. Leakage of liquefied lens cortex behind the posterior capsule is rare. In this paper, we review a case of phacolytic glaucoma in the lens cortex behind posterior capsule. PATIENT CONCERNS: This case report describes a 79-year-old male patient with a 7-year history of progressive blurred vision and a 1-day history of distended in his left eye. He underwent phacoemulsification combined with intraocular lens implantation at our facility 7 years ago. DIAGNOSES: The patient had lower vision (light perception vision) and increased intraocular pressure (IOP) (60 mmHg) in the left eye. Auxiliary inspection found that the left eye had deep anterior chamber depth (around 1 corneal thickness of the peripheral AC angle) as well as vitreous and aqueous humor opacity in the left eye. Combining the clinical symptoms and examinations, we made the diagnosis of PLG in the left eye. INTERVENTIONS: The patient underwent trabeculectomy and extracapsular cataract extraction of the left after a stable ocular condition, during the operation to see that white chyous cortex was visible under the posterior capsule and posterior capsule membrane of the lens was avulsed circularly. OUTCOMES: The postoperative condition was stable. During the follow up of 3 months, the IOP of the left eye was stable without ocular discomfort. LESSONS: This case reported a patient with phacolytic glaucoma in the lens cortex behind posterior capsule who underwent successful surgery, indicating spontaneous capsule rupture can occur in the posterior capsules in PLG and when this situation is detected during the operation, the posterior capsule tearing method can be applied to absorb the lens cortex sticking at the posterior surface of the posterior capsule.
Subject(s)
Cataract Extraction , Cataract , Glaucoma, Open-Angle , Glaucoma , Aged , Humans , Male , Cataract/complications , Glaucoma/surgery , Glaucoma, Open-Angle/surgery , Intraocular PressureABSTRACT
Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease; however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). High-throughput sequencing was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real-time polymerase chain reaction in a small-sample cohort and a large-sample cohort. A total of 276 circRNAs were differentially expressed in the plasma exosomes of CCS patients, with 103 up-regulated and 173 down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels were selected for validation. Real time quantitative PCR of the first and second validation cohort demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS. Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve values of 0.761 (p < 0.001, 95%CI = 0.669, 0.852) and 0.623 (p = 0.015, 95%CI = 0.522, 0.724) for CCS, respectively, by ROC curve analysis. In conclusion, the expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS.
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PURPOSE: This study aims to develop a low-radiation dose, one-step integrated coronary-carotid-cerebral computed tomography angiography (ICCC-CTA) technique to analyze the relationship between cardiovascular and cerebrovascular atherosclerosis and evaluate the risk factors of plaque to provide an early-stage treatment to patients and reduce vascular events. METHODS: A total of 300 consecutive asymptomatic patients with cardiovascular risk factors who underwent ICCC-CTA were enrolled in this prospective study. The association between coronary and carotid-cerebrovascular atherosclerosis was assessed. The primary cardiovascular risk factors for various plaque types in cardiovascular or cerebrovascular disease were evaluated using multivariate analysis. RESULTS: Among 300 patients, 189 (63%) had plaques in their coronary and cerebral arteries. The presence of calcified and mixed plaques in the carotid-cerebral and coronary arteries was strongly correlated (χ2 = 20.71, P = 0.001; χ2 = 8.96, P = 0.003, respectively). Multivariate logistic regression analysis revealed that abnormal blood glucose [OR = 1.44, 95% CI 0.12-0.62, P = 0.01] and abnormal total cholesterol [OR = 1.28, 95% CI 0.07-0.46, P = 0.01] are risk factors in all the models in the coronary artery, non-calcified plaque group. Abnormal blood glucose [OR = 1.43, 95% CI 0.11-0.61, P = 0.01] and abnormal systolic blood pressure [OR = 1.02, 95% CI 0.01-0.04, P = 0.02] are risk factors in all the models in the coronary artery calcified plaque group. Abnormal blood glucose level [OR = 1.44, 95% CI = 0.12-0.62, P = 0.01] was only a risk factor in the non-calcified plaque carotid-cerebral artery group. CONCLUSIONS: We confirm that elevated blood glucose and total cholesterol levels are associated with coronary and carotid-cerebrovascular plaques using the novel one-step low dose cerebral-carotid-cardiac CTA technique. These findings will provide insights for further studies focusing on developing low-radiation dose one-step ICCC-CTA to screen cardiovascular/cerebrovascular plaques in general population with cardiovascular risk factors. ADVANCES IN KNOWLEDGE: We developed a low-radiation dose, one-step ICCC-CTA technique to detect cardiovascular and cerebrovascular atherosclerosis. We evaluated the risk factors for plaque burden for the early treatment and reduction of vascular events. These findings supported the development of low-radiation dose one-step ICCC-CTA to screen for cardiovascular/cerebrovascular disease in general population with cardiovascular risk factors.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Carotid Artery Diseases , Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Computed Tomography Angiography/methods , Prospective Studies , Blood Glucose , Plaque, Atherosclerotic/complications , Carotid Artery Diseases/complications , Cardiovascular Diseases/complications , Risk Factors , Cholesterol , Coronary Angiography/adverse effects , Coronary Artery Disease/complicationsABSTRACT
Introduction: The concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear. Material and methods: A case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients. Results: A total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028). Conclusions: Exosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.
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OBJECTIVES: To evaluate myocardial viability in patients with myocardial ischemia reperfusion injury (MIRI) via dual-energy computed tomography myocardial blood pool imaging (DECT MBPI). METHODS: Between September 2017 and January 2019, we prospectively recruited 59 patients with acute myocardial infarction (AMI) who developed MIRI after revascularization during invasive coronary angiography (ICA). Then, they received DECT MBPI, SPECT, and PET sequentially within 1 week after the onset of MIRI. A total of 1003 myocardial segments of 59 patients were recruited for this study. The iodine reduction areas and delayed enhancement areas were calculated by cardiac iodine map with SPECT rest myocardial perfusion imaging (MPI) + PET myocardial metabolism imaging (MMI) as reference criteria. The paired sample t-test was used to measure the difference of the myocardial iodine value. Cohen's Kappa analysis was used to test the consistency among different observers. ROC analysis was used to calculate the myocardial viability of DECT MBPI. RESULTS: ROC showed the AUCs of DECT MBPI iodine value to identify a normal myocardium, an ischemic myocardium, and an infarcted myocardium were 0.957, 0.900, and 0.906 (p < 0.001). The sensitivity, specificity, and accuracy of DECT MBPI in identifying an ischemic myocardium were 87.6%, 89.3%, and 97.9% (p < 0.001). The sensitivity, specificity, and accuracy of DECT MBPI in identifying an infarcted myocardium were 88.9%, 92.2%, and 98.6% (p < 0.001). The cutoff value for DECT MBPI to differentiate between an ischemic and a normal myocardium was 0.84 mg I/mL. The cutoff value for DECT MBPI to differentiate between an infarct and a normal myocardium was 2.01 mg I/mL. CONCLUSION: DECT MBPI can be used to assess myocardial viability in patients with MIRI with high sensitivity and specificity. KEY POINTS: ⢠Dual-energy computed tomography myocardial blood pool imaging (DECT MBPI) can evaluate myocardial viability of myocardial ischemia-reperfusion injury (MIRI). ⢠DECT MBPI is a non-invasive and timesaving method for evaluation on myocardial ischemia-reperfusion injury in patients with acute myocardial infarction after coronary intervention.
Subject(s)
Iodine , Myocardial Infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Humans , Myocardial Reperfusion Injury/diagnostic imaging , Tomography, X-Ray Computed/methods , Myocardium , Myocardial Infarction/diagnostic imagingABSTRACT
BACKGROUND: Clinical research on exercise-based home pulmonary rehabilitation (HPR) effectiveness in chronic obstructive pulmonary disease (COPD) treatment is rising, as are associated systematic reviews/meta-analyses (SRs/MAs). However, different SRs/MAs vary in outcome indicators, analysis methodologies, literature quality, and findings. This overview aimed to describe the findings of these SRs/MAs and assess their methodological quality. METHODS: From inception until April 2022, we searched PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan Fang. Two researchers searched these SRs/MAs separately, collected the data, and cross-checked it using predetermined rules. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) was used to evaluate the methodological quality of each contained SR/MA. The evidence was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 (PRISMA-2009). The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to determine the validity of the results. RESULTS: A total of 433 records were found, with 44 chosen for full-text review. There were 11 SRs/MAs that matched the inclusion criteria. Our overview included studies published from 2010 to 2022. According to the AMSTAR 2 tool, one had low methodological quality, while the other 10 SRs/MAs had very low quality. The PRISMA statement revealed a low rate of complete reporting for eight items. The GRADE tool, on the other hand, revealed that the evidence quality for most outcomes was very low to moderate. CONCLUSION: According to current research, exercise-based HPR may benefit COPD patients. Nevertheless, this finding is restricted by the low quality of the included SRs/MAs. And more high-quality and large-sample studies are needed in the future. PROSPERO: ID: CRD42022322768. https://www.crd.york.ac.uk/prospero/#recordDetails.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Exercise Therapy , PubMed , Pulmonary Disease, Chronic Obstructive/therapy , Systematic Reviews as TopicABSTRACT
BACKGROUND: 5-Aza-2'-deoxycytidine (5-Aza-CdR) is a demethylating agent that has various biological effects related to DNA methylation. DNA methylation plays important roles in learning and memory. We have reported that 5-Aza-CdR improved the performance of mice in the water maze and step-down tests. Some behaviours have been well recognized to be mediated by neurogenesis in the hippocampus. The Notch signalling pathway plays a key role in adult hippocampal neurogenesis. In this study, we examined whether 5-Aza-CdR (DNA methyltransferase inhibitor) affects neurogenesis and Notch1 expression. METHODS: The learning and memory behaviour of mice was evaluated by a conditioned avoidance learning 24 h after 5-Aza-CdR treatment. The mRNA and protein expression levels of Notch1 and HES1 were measured by real-time PCR and Western blotting. The 5-bromo-2'-deoxyuridine (BrdU)-positive cells and the expression of Notch1 in the hippocampal DG were observed through laser confocal microscopy. To further clarify whether 5-Aza-CdR affects behaviour through neurogenesis, the expression level of Notch1, cell viability and cell cycle were analysed using the HT22 cell line. RESULTS: The behaviour in conditioned avoidance learning was improved, while neurogenesis and the Notch1 pathway were increased in the hippocampus of mice that were injected with 5-Aza-CdR. In vitro experiments showed that 5-Aza-CdR increased the expression of the Notch1 pathway and upregulated S-phase in the cell cycle and cell viability. CONCLUSIONS: Our results suggest that the effect of 5-Aza-CdR on behaviour may be related to an increase in neurogenesis with upregulation of the Notch1 pathway in the hippocampus.
Subject(s)
Azacitidine , Neurogenesis , Animals , Azacitidine/pharmacology , DNA Methylation , Decitabine/pharmacology , Hippocampus , MiceABSTRACT
Background: It has been reported that ischemia and ischemic preconditioning (IPC) have different effects on the expression of tuberous sclerosis complex 1 (TSC1), which may contribute to the tolerance to ischemia/hypoxia with the increase of autophagy. The mechanisms of TSC1 differential expression are still unclear under ischemia/IPC conditions in hippocampal Cornu Ammon 1 (CA1) and Cornu Ammon 3 (CA3) area neuronal cells. While we have shown that 5-Aza-CdR, a DNA methyltransferase inhibitor, can upregulate TSC1 and increase hypoxic tolerance by autophagy in vivo and in vitro, in this study, we examined whether DNA methylation was involved in the differential expression of TSC1 in the CA1 and CA3 regions induced by hypoxic preconditioning (HPC). Methods: Level of rapamycin (mTOR) autophagy, a downstream molecular pathway of TSC1/TSC2 complex, was detected in HPC mouse hippocampal CA1 and CA3 areas as well as in the HPC model of mouse hippocampal HT22 cells. DNA methylation level of TSC1 promoter (-720 bp~ -360 bp) was determined in CA1 and CA3 areas by bisulfite-modified DNA sequencing (BMDS). At the same time, autophagy was detected in HT22 cells transfected with GFP-LC3 plasmid. The role of TSC1 in neuroprotection was measured by cell viability and apoptosis, and the role of TSC1 in metabolism was checked by ATP assay and ROS assay in HT22 cells that overexpressed/knocked down TSC1. Results: HPC upregulated the expression of TSC1, downregulated the level of P-mTOR (Ser2448) and P-p70S6K (Thr389), and enhanced the activity of autophagy in both in vivo and in vitro. The increased expression of TSC1 in HPC may depend on its DNA hypomethylation in the promoter region in vivo. HPC also could reduce energy consumption in HT22 cells. Overexpression and knockdown of TSC1 can affect cell viability, cell apoptosis, and metabolism in HT22 cells exposed to hypoxia. Conclusion: TSC1 expression induced by HPC may relate to the downregulation of its DNA methylation level with the increase of autophagy and the decrease of energy demand.
Subject(s)
Neuroprotection , Ribosomal Protein S6 Kinases, 70-kDa , Adenosine Triphosphate/metabolism , Animals , DNA Methylation/genetics , Gene Expression , Hypoxia/genetics , Hypoxia/metabolism , Methyltransferases/metabolism , Mice , Neuroprotection/genetics , Reactive Oxygen Species , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: Macrophage phenotypes switch from proinflammatory (M1) to anti-inflammatory (M2) following myocardial injury. Implanted stem cells (e.g., induced pluripotent stem cells (iPSCs)) for cardiomyogenesis will inevitably contact the inflammatory environment at the myocardial infarction site. To understand how the macrophages affect the behavior of iPSCs, therefore, improve the therapeutic efficacy, we generated three macrophage subtypes and assessed their effects on the proliferation, cardiac differentiation, and maturation of iPSCs. METHODS: M0, M1, and M2 macrophages were polarized using cytokines, and their properties were confirmed by the expression of specific markers using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The effects of macrophages on iPSCs were studied using Transwell co-culture models. The proliferative ability of iPSCs was investigated by cell counting and CCK-8 assays. The cardiac differentiation ability of iPSCs was determined by the cardiomyocyte (CM) yield. The maturation of CM was analyzed by the expression of cardiac-specific genes using RT-qPCR, the sarcomere organization using immunofluorescence, and the mitochondrial function using oxidative respiration analysis. RESULTS: The data showed that the co-culture of iPSCs with M0, M1, or M2 macrophages significantly decreased iPSCs' proliferative ability. M2 macrophages did not affect the CM yield during the cardiac differentiation of iPSCs. Still, they promoted the maturation of CM by improving sarcomeric structures, increasing contractile- and ion transport-associated gene expression, and enhancing mitochondrial respiration. M0 macrophages did not significantly affect the cardiomyogenesis ability of iPSCs during co-culture. In contrast, co-culture with M1 macrophages significantly reduced the cardiac differentiation and maturation of iPSCs. CONCLUSIONS: M1- or M2-polarized macrophages play critical roles in the proliferation, cardiac differentiation, and maturation of iPSCs, providing knowledge to improve the outcomes of stem cell regeneration therapy. Video abstract.
Subject(s)
Induced Pluripotent Stem Cells , Cell Differentiation , Cell Proliferation , Cytokines/metabolism , Humans , Induced Pluripotent Stem Cells/metabolism , Macrophages/metabolismABSTRACT
At present, artificial intelligence (AI) has already been applied in cardiovascular imaging (e.g., image segmentation, automated measurements, and eventually, automated diagnosis) and it has been propelled to the forefront of cardiovascular medical imaging research. In this review, we presented the current status of artificial intelligence applied to image analysis of coronary atherosclerotic plaques, covering multiple areas from plaque component analysis (e.g., identification of plaque properties, identification of vulnerable plaque, detection of myocardial function, and risk prediction) to risk prediction. Additionally, we discuss the current evidence, strengths, limitations, and future directions for AI in cardiac imaging of atherosclerotic plaques, as well as lessons that can be learned from other areas. The continuous development of computer science and technology may further promote the development of this field.
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BACKGROUND: Synovial sarcoma is a malignant mesenchymal neoplasm with variable epithelial differentiation. Most synovial sarcoma cases are reported in young adults and can arise in any body site. Notably, primary orbital synovial sarcoma is rare. CASE SUMMARY: An 8-year-old east Asian girl with 1-month history of gradual painless proptosis and lacrimation of the right eye was admitted. The patient presented with painless proptosis, downward eyeball displacement, and upward movement disorders. According to clinical manifestations, imaging examinations and postoperative immunohistochemical examinations, the diagnosis was monophasic synovial sarcoma with calcification. The patient underwent anterior orbitotomy procedure for removal of the right orbital mass under general anesthesia. The diagnosis of monophasic synovial sarcoma with calcification was confirmed finally through histological and immunohistochemical exam. The follow-up period was 6 mo, and no recurrence was observed during this period. CONCLUSION: Primary orbital monophasic synovial sarcoma with calcification is a rare sarcoma, and clinical manifestations and imaging results are not specific. The tumor may present similar features as a benign tumor. Comprehensive analysis of clinical, radiological, and pathological findings is critically important for making the right diagnosis. Conventional treatment approach for synovial sarcoma is surgical resection with adjuvant or neoadjuvant radiotherapy, which is highly effective for localized tumors.
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RATIONALE: The presence of cholesterol crystals in the anterior chamber is extremely rare, and secondary glaucoma with cholesterol crystals in the anterior chamber, reported in the literature, is even rarer. This paper reports 3 cases of secondary glaucoma with cholesterol crystals in the anterior chamber. PATIENT CONCERNS: Three patients were admitted to the hospital because of ocular distension and blindness. Ocular examination on admission indicated high intraocular pressure, and crystalline gold substances were observed in the anterior chamber. DIAGNOSIS: Based on clinical manifestations and an aqueous fluid smear, absolute glaucoma and anterior chamber cholesterol crystals were diagnosed. INTERVENTIONS: In the first case, transscleral ciliary photocoagulation was performed; in the last 2 cases, trabeculectomy combined with extracapsular cataract extraction was performed. OUTCOMES: The follow-up period was 11 to 15âmonths. Intraocular pressure was stable in 2 patients treated with surgery, and no cholesterol crystals were observed in the anterior chamber. The intraocular pressure increased in 1 patient treated with laser, and a small amount of cholesterol crystals was still observed in the anterior chamber. LESSONS: Anterior chamber cholesterol crystallization is extremely rare and cannot be treated if it does not cause other lesions. However, glaucoma occurred in all 3 cases in this study, and intraocular pressure increased in 1 case after laser treatment and remained stable in 2 cases after surgical treatment. Therefore, the treatment plan for anterior chamber cholesterol crystallization in glaucoma requires further discussion.
Subject(s)
Anterior Chamber/pathology , Blindness/etiology , Cataract/therapy , Cholesterol , Glaucoma/surgery , Sclera/surgery , Trabeculectomy , Aged, 80 and over , Anterior Chamber/metabolism , Cataract/complications , Cataract Extraction , Female , Glaucoma/complications , Glaucoma/etiology , Humans , Intraocular Pressure , Light Coagulation , Male , Middle Aged , Treatment OutcomeABSTRACT
Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD-PAH) with systemic-to-pulmonary shunt (SPS) is characterized by proliferative vascular remodeling. Capillary morphogenesis gene-2 (CMG2) plays a key role in cell proliferation and apoptosis. This study aimed to determine the role of CMG2 in the pathogenesis of SPS-induced PAH. CMG2 levels were significantly downregulated in pulmonary arterioles from patients with Eisenmenger syndrome and rats with SPS-induced PAH. CMG2 was highly expressed in several cells including human pulmonary arterial smooth muscle cells (HPASMCs). CMG2-/- rats exhibited more severe PAH and pulmonary vascular remodeling than wild-type rats when exposed to SPS for 8 weeks. Overexpression of CMG2 significantly inhibited proliferation and promoted apoptosis of HPASMCs, while knockdown of CMG2 promoted cell proliferation and inhibited cell apoptosis. Next-generation sequencing and subsequent validation results suggested that PI3K-AKT was the most prominent signaling pathway regulated by differentially expressed genes (DEGs) in CMG2-/- rat lungs. Our work identified a novel role for CMG2 in SPS-induced PAH based on the findings that CMG2 deficiency exacerbates SPS-induced vascular remodeling in the development of PAH, indicating that CMG2 might act as a potential target for the treatment of CHD-PAH.
Subject(s)
Eisenmenger Complex/metabolism , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/pathology , Adult , Animals , Apoptosis , Case-Control Studies , Cell Line , Cell Proliferation , Down-Regulation , Endothelial Cells , Gene Deletion , Gene Expression Regulation , Humans , Male , Middle Aged , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Rats , Receptors, Peptide , Vascular Remodeling/physiology , Young AdultABSTRACT
The present study aimed to explore the clinical role of heat shock protein 70 (HSP70) in patients with acute angle-closure glaucoma (AACG). Seventy-four AACG patients who were admitted to our hospital from April 2017 to April 2019 were enrolled as a study group (SG). A further 70 healthy people undergoing physical examinations during the same period were enrolled as a control group (CG). HSP70 concentration was compared between the two groups, and the clinical value of this protein in AACG was analyzed. HSP70 concentration in SG was significantly lower than that in CG (P<0.050). The sensitivity and specificity of HSP70 for diagnosing AACG were 79.73 and 74.29%, respectively (P<0.001). HSP70 concentration was positively correlated with central anterior chamber depth and peripheral anterior chamber depth, but negatively correlated with anterior angle and intraocular pressure (P<0.001). HSP70 had a relatively satisfactory predictive value for adverse reactions during the treatment (P<0.001). HSP70 concentration was markedly reduced in AACG patients, and its detection had a relatively satisfactory predictive value for AACG. Thus, HSP70 may be a potential and notable indicator for diagnosing and treating glaucoma in the future.
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Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one of the primary causes of cerebrovascular and cardiovascular events. Neovascularization within the plaque is closely associated with its stability. Long non-coding RNA (lncRNA) serves a crucial role in regulating vascular endothelial cells (VECs) proliferation and angiogenesis. In this study, we identified lncRNA HCG11, which is highly expressed in patients with vulnerable plaque compared with stable plaque. Then, functional experiments showed that HCG11 reversed high glucose-induced vascular endothelial injury through increased cell proliferation and tube formation. Meanwhile, vascular-related RNA-binding protein QKI5 was greatly activated. Luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP) assays verified interaction between them. Interestingly, HCG11 can also positively regulated by QKI5. Bioinformatics analysis and luciferase reporter assays showed HCG11 can worked as a competing endogenous RNA by sponging miR-26b-5p, and QKI5 was speculated as the target of miR-26b-5p. Taken together, our findings revered that the feedback loop of lncRNA HCG11/miR-26b-5p/QKI-5 played a vital role in the physiological function of HUVECs, and this also provide a potential target for therapeutic strategies of As.
Subject(s)
Gene Expression Regulation , Glucose/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , MicroRNAs/genetics , Neovascularization, Physiologic/genetics , RNA, Long Noncoding/genetics , RNA-Binding Proteins/genetics , Aged , Biomarkers , Cell Line, Tumor , Cells, Cultured , Female , Genes, Reporter , Glucose/pharmacology , Humans , Male , Middle Aged , RNA InterferenceABSTRACT
Exosomes are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized in acute myocardial infarction (AMI). However, the regulatory role of exosomal long non-coding RNAs (lncRNAs) in AMI remains largely unclear. Exosomes were isolated from the plasma of AMI patients and controls, and the sequencing profiles and twice qRT-PCR validations of exosomal lncRNAs were performed. A total of 518 differentially expressed lncRNAs were detected over two-fold change, and 6 kinds of lncRNAs were strikingly elevated in AMI patients with top fold change and were selected to perform subsequent validation. In the two validations, lncRNAs ENST00000556899.1 and ENST00000575985.1 were significantly up-regulated in AMI patients compared with controls. ROC curve analysis revealed that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 yielded the area under the curve values of 0.661 and 0.751 for AMI, respectively. Moreover, ENST00000575985.1 showed more significant relationship with clinical parameters, including inflammatory biomarkers, prognostic indicators and myocardial damage markers. Multivariate logistic model exhibited positive association of ENST00000575985.1 with the risk of heart failure in AMI patients. In summary, our data demonstrated that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 are elevated in patients with AMI, functioning as potential biomarkers for predicting the prognosis of pateints with AMI.