RESUMO
BACKGROUND: Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI). METHODS: A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open-field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome-related protein expression via Western blotting and immunofluorescence. RESULTS: SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive-like behavior. Compared to the Sham group, levels of IL-1ß, IL-18, TNF-α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome-related proteins in the hippocampus revealed a significant upregulation of IL-1ß, IL-18, NLRP3, ASC, caspase-1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention. CONCLUSION: We have observed a significant amelioration in depression-like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3-mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.).
Assuntos
Antidepressivos , Depressão , Medicamentos de Ervas Chinesas , Inflamassomos , Infarto do Miocárdio , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/complicações , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Ratos , Depressão/tratamento farmacológico , Depressão/etiologia , Antidepressivos/farmacologia , Antidepressivos/administração & dosagem , Masculino , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacosRESUMO
In this study, the significance of oxidized low-density lipoprotein (ox-LDL) in promoting the progression of atherosclerosis was investigated by inducing the differentiation of macrophages into the M2 subtype within a high-fat diet-induced ApoE -/- mouse model. The study also evaluated the effects of ß2-AR agonists and blockers on this process. Ox-LDL was found to have significantly promoted the differentiation of macrophages into the M2 type and induced related functional alterations. Furthermore, it activated the pyroptosis pathway and encouraged the release of lactate dehydrogenase. The administration of ß2-AR agonists intensified these processes, while ß2-AR blockers had the opposite effect. In animal experiments, the model group displayed elevated numbers of M2-type macrophages beneath the aortic root intima, an increased rate of plaque destruction, and the formation of atherosclerotic plaques compared to the control group. The SAL (Salbutamol) group exhibited even more severe plaque development than the model group. Conversely, the ICI (ICI118551) group demonstrated M2-type macrophage levels comparable to the control group, with a higher plaque destruction rate than controls but significantly lower than the model group, and no atherosclerotic plaques. These findings suggest that ox-LDL promoted the differentiation of recruited monocytes into M2-type macrophages, leading to a shift in the inflammatory response from M1 to M2 macrophages. This alteration resulted in the persistence of atherosclerotic inflammation, as M2-type macrophages were prone to cell membrane rupture (such as pyroptosis), contributing to the continuous recruitment of circulating monocytes and heightened inflammatory reactions within atherosclerotic plaques. Consequently, this process fueled the progression of atherosclerosis.
Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , Placa Aterosclerótica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Knockout para ApoE , Aterosclerose/metabolismo , Macrófagos , Lipoproteínas LDL/farmacologia , Lipoproteínas LDL/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Background: To investigate the expression of Th17, T lymphocyte immunoglobulin mucin 3 (TIM-3+) cells and their related cytokines in atrial fibrillation (AF) and their clinical significance. Methodology: A total of 90 patients with AF were divided into paroxysmal group (n=45) and chronic group (n=45), and 45 healthy volunteers were selected as the control group. The proportion of Th17 cells and Tim-3 + cells in the peripheral blood were detected. The concentrations of related cytokines in peripheral blood serum were determined. The correlation between Th17 / Tim-3+ cells and related cytokines was analysed. Results: Compared with the control group, the proportion of Th17 cells and the concentration of related cytokines (IL-17, IL-6 and Matrix metalloproteinase (MMP9)) in peripheral blood of patients with paroxysmal and chronic AF increased significantly, while the proportion of tim3 + cells and the concentration of related cytokines decreased significantly. Compared with the paroxysmal group, the proportion of Th17 cells and the concentration of related cytokines in the peripheral blood of patients in the chronic group increased significantly, while the proportion of tim3 + cells and the concentration of related cytokines decreased significantly. Conclusion: Th17 / Tim-3 + cell balance is involved in AF, and can be used as a target for AF treatment.
Assuntos
Fibrilação Atrial , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Mucina-3/metabolismo , Fibrilação Atrial/etiologia , Citocinas/metabolismo , Células Th17/metabolismo , Células Th17/patologia , Imunoglobulinas/metabolismoRESUMO
A healthy 31-year-old Chinese Han female donated peripheral blood mononuclear cells (PBMC). Her PBMCs were reprogrammed with human OKSM (OCT3/4, KLF4 SOX2, and c-MYC) transcription factors by the non-integrating episomal vector system. Immunocytochemistry for pluripotency markers confirmed the pluripotency of transgene-free iPSCs. Their ability to differentiate spontaneously three germ layers in vitro is also confirmed. The iPSC line displayed a normal karyotype. This model can be used as a control in pathological mechanism studies.
Assuntos
Células-Tronco Pluripotentes Induzidas , Adulto , Diferenciação Celular , China , Feminino , Patrimônio Genético , Humanos , Fator 4 Semelhante a Kruppel , Leucócitos Mononucleares , Fatores de TranscriçãoRESUMO
Induced pluripotent stem cells play vitally essential roles in regenerative medicines for disease modeling and drug screening. Here, we successfully generated an iPSC line from PBMC of a 60-year-old female with mild cognitive impairment in an APOE 4/4 background to better understand studies relating to MCI and other cognitive diseases. In the newly-developed hiPSC line SIAISi009-A, all pluripotent markers were well expressed. Moreover, cells displayed a normal karyotype and have differentiation potential proven by in vitro trilineage differentiation method.
Assuntos
Disfunção Cognitiva , Células-Tronco Pluripotentes Induzidas , Alelos , Apolipoproteína E4/genética , China , Disfunção Cognitiva/genética , Feminino , Humanos , Leucócitos Mononucleares , Pessoa de Meia-IdadeRESUMO
As the global median population age increases, neurological diseases associated with aging pose significant challenges to human health. Appropriate modeling systems can be useful tools to better understand the mechanism of age-related neuronal degeneration diseases. Here, we successfully generated an iPSC-derived modeling system of an 82-year-old healthy man, this newly established line showed that all pluripotent markers were expressed, and the differentiation potential was confirmed by trilineage differentiation. STR profiling proved the cell line identity, and G-binding showed the normal karyotype.
Assuntos
Células-Tronco Pluripotentes Induzidas , Idoso de 80 Anos ou mais , Diferenciação Celular , Linhagem Celular , China , Humanos , MasculinoRESUMO
A 66-year-old Chinese Han Alzheimer's Disease (AD) female patient and her two unaffected children donated their Peripheral blood mononuclear cells (PBMC). Non-integrating episomal vector system were used to reprogram their PBMCs with human OKSM (OCT3/4, KLF4, SOX2, and c-MYC) transcription factors. Immunocytochemistry for pluripotency makers confirmed the pluripotency of transgene-free iPSCs. Pluripotency was confirmed by the ability of iPSCs to spontaneously differentiate three germ layers in vitro as well. The iPSC line displayed a normal karyotype. This model provides insight into further pathological studies to research identify early biomarkers, study disease pedigrees, and also for drug testing purposes.
Assuntos
Doença de Alzheimer , Células-Tronco Pluripotentes Induzidas , Idoso , Doença de Alzheimer/genética , Diferenciação Celular , Linhagem Celular , Criança , China , Feminino , Humanos , Fator 4 Semelhante a Kruppel , Leucócitos MononuclearesRESUMO
Peripheral blood mononuclear cells (PBMC) were donated by a healthy 61-year old Chinese Han female. Human OKSM (OCT3/4, KLF4 SOX2, and c-MYC) transcription factors were used to reprogram her PBMCs with the non-integrating episomal vector system. Immunocytochemistry for pluripotency makers confirmed the pluripotency of transgene-free iPSCs and their ability to differentiate spontaneously three germ layers in vitro. The iPSC line displayed a normal karyotype. Our model offers the possibility to be used a control in pathological mechanism studies.
Assuntos
Células-Tronco Pluripotentes Induzidas , China , Feminino , Humanos , Fator 4 Semelhante a Kruppel , Leucócitos Mononucleares , Pessoa de Meia-Idade , Fatores de Transcrição , TransgenesRESUMO
The genotype of apolipoprotein E (APOE) is closely associated with susceptibility to Alzheimer's disease. Here, we described the generation and characterization of human induced pluripotent stem cells from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female patient with Alzheimer's disease having APOE3/4 genotype. The generated iPSCs expressed pluripotent stem cell markers that were observed using immunocytochemistry. Moreover, they displayed a normal karyotype and had the potential to differentiate spontaneously into three germ layers in vitro. Our model could provide valuable insights into pathological mechanisms, and offer a unique opportunity for developing drugs against specific phenotypes for Alzheimer's disease therapy.