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1.
Front Cardiovasc Med ; 11: 1351567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854655

RESUMO

Background: ST-segment elevation myocardial infarction (STEMI) persists to be prevalent in the elderly with a dismal prognosis. The capacity of endothelial progenitor cells (EPCs) is reduced with aging. Nevertheless, the influence of aging on the functionality of EPCs in STEMI is not fully understood. Method: This study enrolled 20 younger STEMI patients and 21 older STEMI patients. We assessed the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events Risk (GRACE) scores in two groups. Then, we detected EPC migration, proliferation, adhesion, and plasma interleukin (IL)-18 and IL-23 concentrations in two groups. In addition, we analyzed the interconnection between age, EPC function, plasma IL-18 and IL-23 concentrations, and GRACE or TIMI scores in STEMI patients. Result: GRACE and TIMI scores in older STEMI patients were higher than in younger STEMI patients, whereas EPC function declined. GRACE and TIMI scores were found to have an inverse relationship with the EPC function. In older STEMI patients, plasma concentrations of IL-18 and IL-23 increased. Plasma IL-18 and IL-23 concentrations were adversely connected to EPC capacity and positively related to GRACE and TIMI scores. Moreover, age was positively correlated with plasma IL-18 or IL-23 concentrations, as well as GRACE or TIMI scores. However, age was adversely correlated with EPC function. Conclusion: In patients with STEMI, aging results in declined EPC function, which may be associated with inflammatory cytokines. The current investigation may offer new perception about mechanism and therapeutic targets of aging STEMI.

2.
Oxid Med Cell Longev ; 2022: 2281870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795858

RESUMO

Background: Aging is an independent risk factor for heart failure (HF), and endothelial progenitor cell (EPC) function decreases with aging. Here, we further investigated whether age has a detrimental effect on circulating EPC function in HF with mildly reduced ejection fraction (HFmrEF) and its relationship with systemic inflammation. Methods: 58 HFmrEF patients were recruited. The adhesive, migrative, and proliferative activities of circulating EPCs, MAGGIC scores, and plasma interleukin (IL)-17 and IL-23 levels of these patients were assessed. Results: Older patients with HFmrEF had higher MAGGIC scores and lower circulating EPC adhesion, migration, and proliferation than younger patients. The similar tendency was observed in plasma IL-17 and IL-23 levels. The EPC functions were negatively associated with MAGGIC scores and plasma IL-17 or IL-23 levels. Conclusions: In patients with HFmrEF, aging leads to attenuated circulating EPC function, which is correlated with disease severity and systemic inflammation. The present investigation provides some novel insights into the mechanism and intervention targets of HFmrEF.


Assuntos
Células Progenitoras Endoteliais , Insuficiência Cardíaca , Interleucina-17 , Interleucina-23 , Fatores Etários , Células Progenitoras Endoteliais/metabolismo , Insuficiência Cardíaca/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-17/metabolismo , Interleucina-23/metabolismo
3.
Oxid Med Cell Longev ; 2022: 2939279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571255

RESUMO

Background: Sepsis-induced cardiomyopathy (SIC) is a sort of severe disease in the intensive care unit. This research focuses on exploring the influence of miR-340-5p on SIC and its specific mechanism. Methods: Mice were administered with lipopolysaccharide (LPS) to construct a SIC animal model. Mice were intramyocardially injected with Adenoassociated Virus- (AAV-) 9 containing the miR-340-5p precursor to make the miR-340-5p overexpression in the myocardium. The expression level of myocardial miR-340-5p was evaluated by qRT-PCR. The cardiac function was measured by echocardiography, the myocardial morphology was observed by hematoxylin-eosin (HE) staining, and the oxidative stress level was detected by 4-hydroxynonenal (4-HNE) immunohistochemical staining and malondialdehyde (MDA) assay in mice. The cells were pretreated with miR-340-5p mimic, mimic-NC, miR-340-5p inhibitor, inhibitor-NC, MyD88 siRNA, or si-NC and then administered with LPS or PBS. The cell viability was measured with the CCK-8 assay. The level of intracellular oxidative stress was evaluated using reactive oxygen species (ROS), MDA, and glutathione (GSH) detection. The MyD88 level was assessed via Western blotting analysis. The interaction of miR-340-5p with the MyD88 mRNA was confirmed via dual-luciferase reporter assay and RNA pull-down assay. Results: The miR-340-5p overexpression partially alleviated the increase of the MyD88 level, impairment of cardiac function, and oxidative stress injury in the SIC animal model. In the SIC cell model, miR-340-5p mimic pretreatment partially relieved oxidative stress injury, while the miR-340-5p inhibitor had the opposite effect. Besides, the miR-340-5p mimic and inhibitor could reduce and further increase the MyD88 level in the SIC cell model, respectively. Dual-luciferase reporter and RNA pull-down experiments confirmed the interaction between the MyD88 mRNA and miR-340-5p. Finally, it was found that MyD88 siRNA pretreatment also partially alleviates the oxidative stress injury in the SIC cell model. Conclusion: In sum, our study demonstrated that miR-340-5p can improve myocardial oxidative stress injury by targeting MyD88 in SIC.


Assuntos
Cardiomiopatias , MicroRNAs , Sepse , Animais , Apoptose , Cardiomiopatias/genética , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Sepse/complicações , Sepse/genética , Sepse/metabolismo
4.
Cardiol Res Pract ; 2022: 4287711, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600333

RESUMO

Cardiovascular disease (CVD) is a serious public health issue in China, accounting for more than 40% of all mortality, and it is the leading cause of death worldwide. Atherosclerosis is the pathological basis for much CVD, including coronary heart disease, acute myocardial infarction, and stroke. Endothelial dysfunction is an initiating and exacerbating factor in atherosclerosis. Recent research has linked oxidative stress and mitochondrial damage to endothelial dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor with antioxidant effects that is strongly connected to several CVDs. However, the mechanism by which Nrf2 reduces CVD is unknown. Research indicates that Nrf2 improves endothelial function by resisting oxidative stress and mitochondrial damage, thereby delaying atherosclerosis. This article examines the mechanisms and potential targets of Nrf2 affecting endothelial cell function to improve atherosclerosis and to provide ideas for the development of new CVD treatments.

5.
Cardiol Res Pract ; 2022: 6558060, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600331

RESUMO

Cardiovascular disease, especially coronary artery disease and stroke, kills around one-third of the world's population, and myocardial infarction, a primary symptom of coronary heart disease, is a major worldwide health problem. Cardiovascular disease research has historically focused on promoting angiogenesis following myocardial damage. Myocardial vascular repair is crucial for improving myocardial infarction prognosis. Endothelial cells, the largest population of nonmyocytes within myocardial tissue, play an important role in angiogenesis. In recent years, different types of programmed cell death such as apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy have been described and found to be linked with cardiovascular diseases such as myocardial infarction, heart failure, and myocarditis. This will have important implications for reforming the treatment strategy of cardiovascular diseases. Different types of cell death of endothelial cells in myocardial infarction have been proposed, the roles and mechanisms of endothelial cell death in myocardial infarction are summarized in this review, and endothelial cell death inhibition as a therapeutic technique for treating myocardial infarction might be advantageous to human health.

6.
Simul Healthc ; 17(1): e68-e74, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35104832

RESUMO

INTRODUCTION: The flipped classroom (FC) approach and high-fidelity patient simulation (HFPS) training have shown promising effects in short-term acquisition or long-term retention of knowledge in medical education. In this study, we aimed to explore the incorporation of HFPS into the FC and the impact on the long-term (3 months after classes) knowledge retention of medical undergraduate students learning about acute organophosphorus pesticide poisoning (AOPP). METHODS: Eighty-two fifth-year medical students were randomly divided into an HFPS group (HG, n = 40) and an FC group (FG, n = 42). A postclass quiz and preinternship quiz were performed to assess the short-term knowledge acquisition and long-term (3 months after classes) knowledge retention of both groups of students. Feedback questionnaires were administered immediately after the class and before the internship to assess the students' self-perceived competency. RESULTS: In the postclass quiz, the scores achieved by the students from the HG and FG were 15.58 ± 2.69 and 14.62 ± 2.19, respectively. No significant difference was found between the 2 groups (P = 0.19). In the preinternship quiz, the scores achieved by the students from the HG (14.50 ± 2.16) were significantly higher than those achieved by the students from the FG (11.40 ± 2.07, P < 0.001). There was no significant difference between the postclass quiz and preinternship quiz scores achieved by the HG students (P = 0.05). However, scores in the preinternship quiz showed a significant decline compared with the postclass quiz for the FG students (P < 0.001). Students in the HG gave significantly higher scores for self-perceived confidence in dealing with AOPP patients in the forthcoming internship on the postclass and preinternship questionnaires. CONCLUSIONS: The incorporation of HFPS into the FC approach could improve students' long-term knowledge retention of AOPP and enhance their confidence in caring for these patients in their internship.


Assuntos
Internato e Residência , Praguicidas , Estudantes de Medicina , Humanos , Compostos Organofosforados , Simulação de Paciente
7.
Front Psychol ; 12: 691183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367015

RESUMO

The present work aims to boost tourism development in China, grasp the psychology of tourists at any time, and provide personalized tourist services. The research object is the tourism industry in Macau. In particular, tourists' experiences are comprehensively analyzed in terms of dining, living, traveling, sightseeing, shopping, and entertaining as per their psychological changes using approaches including big data analysis, literature analysis, and field investigation. In this case, a model of tourism experience formation path is summarized, and a smart travel solution is proposed based on psychological experience. In the end, specific and feasible suggestions are put forward for the Macau tourism industry. Results demonstrate that the psychology-based smart travel solution exerts a significant impact on tourists' tourism experience. Specifically, the weight of secular tourism experience is 0.523, the weight of aesthetic tourism experience is 0.356, and the weight of stimulating tourism experience is 0.121. Tourists prefer travel destinations with excellent urban security and scenic authenticity. They give the two indexes comprehensive scores of 75.14 points and 73.12 points, respectively. The proposed smart travel solution can grasp the psychology of tourists and enhance their tourism experiences. It has strong practical and guiding significances, which can promote constructing smart travel services in Macau and enhancing tourism experiences.

8.
Front Cardiovasc Med ; 8: 687590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222381

RESUMO

Background: Aging patients easily suffer from non-ST segment elevation myocardial infarction (NSTEMI). Our previous studies revealed declined function of endothelial progenitor cells (EPCs) in the elderly. However, the impact of aging on EPC function and severity in male NSTEMI patients and its possible mechanism is unclear until now. Methods: We measured the circulating EPC function including migration, proliferation, and adhesion in aging or young male patients with NSTEMI. The GRACE and TIMI risk score were evaluated. Plasma levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) were also detected in all patients. Results: Compared with the young group, the old male patients with NSTEMI had higher GRACE score and TIMI score and decreased function of circulating EPCs. EPC function was negatively correlated with GRACE score and TIMI score. IL-6 and IL-17 level were higher in the old group than those in the young group. There was a significant negative correlation between EPC function and IL-6 or IL-17. Moreover, IL-6 and IL-17 positively correlated with GRACE and TIMI score. Age was positively related with GRACE or TIMI score and plasma level of IL-6 or IL-17, but inversely correlated with EPC function. Conclusions: The current study firstly illustrates that the age-related decrement in EPC function is related to the severity of NSTEMI in male patients, which may be connected with systemic inflammation. These findings provide novel insights into the pathogenetic mechanism and intervention target of aging NSTEMI.

9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(5): 511-520, 2021 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34148888

RESUMO

OBJECTIVES: The Fourth Plenary Session of the 19th Central Committee of the Communist Party of China put forward the idea of "promoting the equalization of basic public services". The utilization of basic public health services by the floating population is an important indicator to measure the equalization of basic public health services. This study aims to understand the intergenerational differences in the utilization of basic public health services between the older generation and the new generation of floating population, and to analyze the influential factors. METHODS: We employed the personal questionnaire (A) of the national health and family planning dynamic monitoring survey on floating population in 2017. Pearson Chi-square test, bi-grouping logistic regression, and Poisson regression were applied to analyze the basic situation of the floating population and the intergenerational differences in the use of basic public health services between the new and old generations. RESULTS: The proportions of the new generation and the old generation who had established the residents' health records in the inflow area were 36.42% and 34.96%, respectively, with the significant difference (P<0.01). In the new generation, 74.07% of the floating population received at least one health education, 5.33 percentage higher than that in the old generation. The proportion of the old generation in the health education of chronic disease prevention and control was significantly higher than that of the new generation (P<0.01). The proportions of the other eight kinds of health education were significantly lower than those of the new generation (all P<0.05). CONCLUSIONS: Although the coverage of basic public health services for the two generations of floating population is obviously different, the utilization of basic public health services of the floating population is still at a low level both in the new generation and in the old generation. There is an urgent need to improve the utilization of public health services for the whole floating population according to the characteristics of generations.


Assuntos
Serviços de Saúde , População Rural , China/epidemiologia , Escolaridade , Humanos , População Urbana
10.
Front Mol Biosci ; 7: 573327, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330617

RESUMO

BACKGROUND: To this day, the molecular mechanism of endotoxin-induced multi-organ failure has not been completely clarified. This study aimed to construct an miRNA-mRNA regulatory network and identify main pathways and key genes in multi-organ of LPS-mediated endotoxemic mice. METHODS: Public datasets from six mRNA and three miRNA microarray datasets were downloaded from the GEO website to screen final differentially expressed genes (FDEGs) and hub genes in the heart, lung, liver, and kidney of LPS-mediated endotoxemic mice. Functional and pathway enrichment analysis of FDEGs was used to identify the main pathways in multi-organ damage of LPS-treated mice. Finally, hub genes of each organ were intersected to obtain the key genes of multi-organ. RESULTS: Firstly, 158, 358, 299, and 91 FDEGs were identified in the heart, lung, liver, and kidney, respectively. The pathway enrichment analysis of the FDEGs then showed that the TNF signaling pathway, Toll-like receptor signaling pathway, and some viral-infection-related pathways (influenza A, measles, and herpes simplex) were the main pathways in multi-organ damage of LPS-mediated endotoxemic mice. Moreover, miRNA-mRNA or PPI regulatory networks were constructed based on FDEGs. According to these networks, 31, 34, 34, and 31 hub genes were identified in the heart, lung, liver, and kidney, respectively. Among them, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) were enriched in Toll-like receptor signaling pathway and chemokine signaling pathway. Finally, seven potential drugs were predicted based on these key genes. CONCLUSION: The shared underlying molecular pathways in endotoxin-induced multi-organ damage that have been identified include Toll-like receptor signaling pathway and TNF signaling pathway. Besides, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) and seven potential drugs were identified. Our data provide a new sight and potential target for future therapy in endotoxemia-induced multi-organ failure.

11.
Cardiol Res Pract ; 2020: 5010243, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204526

RESUMO

Hyperhomocysteinemia (HHcy) induced endothelial dysfunction is associated with disturbance in circulating endothelial progenitor cells (EPCs). Nevertheless, whether this unfavorable effect of HHcy on circulating EPCs also exists in premenopausal women is still unknown. Therefore, this leaves an area for the investigation of the difference on the number and activity of circulating EPCs in premenopausal women with hyperhomocysteinemia and its underlying mechanism. The number of circulating EPCs was measured by fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining. The migration and proliferation of circulating were evaluated by the Transwell chamber assay and MTT. Additionally, the endothelial function and levels of nitric oxide (NO), VEGF, and GM-CSF in plasma and culture medium were determined. The number or activity of circulating EPCs and flow-mediated dilatation (FMD) in premenopausal women with or without HHcy were higher than those in postmenopausal women. However, no significant effect of HHcy on the number or activity of circulating EPCs in premenopausal women was observed. A similar alteration in NO level between the four groups was observed. There was a correlation between FMD and the number or activity of EPCs, as well as NO level in plasma or secretion by EPCs. For the first time, our findings illuminated the quantitive or qualitative alterations of circulating EPCs and endothelial function in premenopausal patients with HHcy are preserved, which was associated with retained NO production. The recuperated endothelial repair capacity is possibly the potential mechanism interpreting cardiovascular protection in premenopausal women with HHcy.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32754448

RESUMO

Viral myocarditis (VMC) is a disease characterized as myocardial parenchyma or interstitium inflammation caused by virus infection, especially Coxsackievirus B3 (CVB3) infection, which has no accurate non-invasive examination for diagnosis and specific drugs for treatment. The mechanism of CVB3-induced VMC may be related to direct myocardial damage of virus infection and extensive damage of abnormal immune response after infection. Non-coding RNA (ncRNA) refers to RNA that is not translated into protein and plays a vital role in many biological processes. There is expanding evidence to reveal that ncRNAs regulate the occurrence and development of VMC, which may provide new treatment or diagnosis targets. In this review, we mainly demonstrate an overview of the potential role of ncRNAs in the pathogenesis, diagnosis and treatment of CVB3-induced VMC.


Assuntos
Infecções por Coxsackievirus , Miocardite , Animais , Infecções por Coxsackievirus/diagnóstico , Modelos Animais de Doenças , Enterovirus Humano B/genética , Camundongos , Camundongos Endogâmicos BALB C , Miocárdio , RNA não Traduzido/genética
13.
Chin Med ; 15: 8, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31993073

RESUMO

BACKGROUND: Atherosclerosis, the underlying cause of the majority of cardiovascular diseases, is a lipid-driven, inflammatory disease of the large arteries. Atherosclerotic cardiovascular disease (ASCVD) threatens human lives due to high morbidity and mortality. Many studies have demonstrated that atherosclerosis is accelerated via activation of the NLRP3 inflammasome. The NLRP3 inflammasome plays a critical role in the development of vascular inflammation and atherosclerosis. In atherosclerotic plaques, excessive generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome. 13-Methylberberine (13-MB) is a newly synthesized compound used in traditional Chinese medicine that has outstanding antibacterial, antitumor, and antiobesity activities, especially anti-inflammatory activity. However, the role of 13-MB in atherosclerosis needs to be explored. METHODS: CCK-8 assays and flow cytometry were conducted to determine the cell viability and apoptotic profiles of human umbilical vein endothelial cells (HUVECs) treated with 13-MB. Carboxy-DCFH-DA and JC-10 assays were used to measure ROS and determine mitochondrial membrane potential. Western blot analysis was performed to investigate proteins that are associated with the NLRP3 inflammasome and autophagy. ELISA was used to detect and quantify inflammatory cytokines related to the NLRP3 inflammasome. Transfection and confocal microscopy were conducted to observe autophagy. RESULTS: Pretreatment with 13-MB markedly reduced cytotoxicity and apoptosis, as well as intracellular ROS production, in H2O2-induced HUVECs. Moreover, 13-MB showed a protective effect in maintaining mitochondrial membrane potential. 13-MB also suppressed NLRP3 inflammasome activation and promoted autophagy induction in HUVECs. CONCLUSION: 13-MB exerts cytoprotective effects in an H2O2-induced cell injury model by inhibiting NLRP3 inflammasome activation via autophagy induction in HUVECs. These anti-inflammatory and autophagy induction activities may provide valuable evidence for further investigating the potential role of 13-MB in atherosclerosis.

14.
Am J Transl Res ; 10(4): 1109-1116, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736204

RESUMO

This study was performed to evaluate the cardioprotective effects of osthole (OST) in a rat model of myocardial ischemia/reperfusion injury (MI/RI) and the underlying mechanism. We exposed rat hearts to left anterior descending coronary artery ligation for 30 min followed by 24 h of reperfusion. The results showed that pretreatment with OST ameliorated MI/RI as evidenced by histopathological examination. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay demonstrated that OST suppressed myocardial apoptosis, which may be related to an increase in the Bcl-2/Bax ratio and inhibition of caspase-3 and caspase-9 activation. Furthermore, we determined that OST ameliorated impaired mitochondrial morphology and the oxidation system; OST also attenuated levels of pro-inflammatory cytokines, including tumor necrosis factor α and interleukins 6 and 1ß. In conclusion, OST exerted a strong favorable cardioprotective effect on MI/RI, possibly by suppressing the inflammatory response and inhibiting cell apoptosis.

15.
RSC Adv ; 8(25): 13739-13746, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35539337

RESUMO

The aim of this study was to investigate the effects of chrysin (CH) on myocardial ischemia-reperfusion injury. Cytokines were reduced by CH in coronary artery occlusion-induced rats and also in H9C2 cells. The ST segment was also restored by CH. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that CH could alleviate myocardial injury. Results in H9C2 cells showed that CH improved heart injury in hypoxia/reoxygenation (H/R) of H9C2 cells. In addition, the expressions of the HMGB1-related inflammation pathway in rats and H9C2 cells were significantly decreased by CH. The present study shows the protective effects of CH on myocardial injury via inflammation.

16.
J Cell Physiol ; 233(10): 6613-6620, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29215742

RESUMO

We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real-time polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference-mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.


Assuntos
Adipocinas/genética , Hipertensão/genética , Apneia Obstrutiva do Sono/genética , Receptor 4 Toll-Like/genética , Adipócitos/metabolismo , Adiponectina/genética , Animais , Citocinas/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Hipertensão/complicações , Hipertensão/patologia , Interleucina-6/genética , Interleucina-8/genética , Leptina/genética , Masculino , Nicotinamida Fosforribosiltransferase/genética , RNA Interferente Pequeno/genética , Ratos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/patologia , Receptor 4 Toll-Like/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética
17.
Mol Pain ; 13: 1744806917747425, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29166835

RESUMO

Oxaliplatin-induced chronic painful neuropathy is the most common dose-limiting adverse event that negatively affects cancer patients' quality of life. However, the underlying molecular mechanisms are still unclear. In the present study, we found that the intraperitoneal administration of oxaliplatin at 4 mg/kg for five consecutive days noticeably upregulated the expression of CXC motif ligand 12 (CXCL12) in the dorsal root ganglion, and the intrathecal injection of an anti-CXCL12 neutralizing antibody or CXCL12 siRNA attenuated the mechanical allodynia and thermal hyperalgesia induced by oxaliplatin. We also found that the signal transducers and transcription activator 3 (STAT3) was activated in the dorsal root ganglion, and inhibition of STAT3 with S3I-201 or the injection of AAV-Cre-GFP into STAT3flox/flox mice prevented the upregulation of CXCL12 expression in the dorsal root ganglion and chronic pain following oxaliplatin administration. Double-label fluorescent immunohistochemistry findings also showed that p-STAT3 was mainly localized in CXCL12-positive cells in the dorsal root ganglion. Furthermore, the results of a chromatin immunoprecipitation assay revealed that p-STAT3 might be essential for oxaliplatin-induced CXCL12 upregulation via binding directly to the specific position of the CXCL12 gene promoter. Finally, we found that cytokine TNF-α and IL-1ß increases mediated the STAT3 activation following oxaliplatin treatment. Taken together, these findings suggested that the upregulation of CXCL12 via TNF-α/IL-1ß-dependent STAT3 activation contributes to oxaliplatin-induced chronic pain.


Assuntos
Quimiocina CXCL12/metabolismo , Dor Crônica/induzido quimicamente , Dor Crônica/metabolismo , Gânglios Espinais/metabolismo , Compostos Organoplatínicos/efeitos adversos , Fator de Transcrição STAT3/metabolismo , Regulação para Cima , Animais , Quimiocina CXCL12/genética , Dor Crônica/patologia , Hiperalgesia/complicações , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Interleucina-1beta/metabolismo , Masculino , Oxaliplatina , Fosforilação , Regiões Promotoras Genéticas/genética , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
18.
Mol Med Rep ; 16(5): 6405-6411, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901399

RESUMO

Macrophage polarization is flexible, and involves in different signaling pathways and various transcription factors. Suppressor of cytokine signaling (SOCS) is an important inhibitor of cytokine signaling pathways and also a key physiological regulator for natural and acquired immunity systems. Following transfection of SOCS1 short hairpin (sh)RNA into mouse macrophage cells, reverse transcription­quantitative polymerase chain reaction demonstrated that the mRNA levels of Janus kinase (JAK)1 and signal transducer and activator of transcription (STAT)1 increased significantly. In addition, western blotting indicated that JAK1, STAT1 and p­STAT1 expression was significantly enhanced. Fludarabine can inhibit phosphorylation of STAT1 and SOCS1 expression. When fludarabine was added and SOCS1 shRNA was transfected, the inhibition of fludarabine was weakened, and p­STAT1 expression was upregulated. Flow cytometry detection indicated that, following the downregulation of SOCS1 expression, M1­type cells significantly increased, but the proportion of M2­type cells did not change significantly. Fludarabine can reduce the effect of SOCS1 shRNA on promoting M1­type cell polarization, and macrophages can polarize into both M1 and M2 phenotypes. Further ELISA results presented that, when downregulating SOCS1 expression, interleukin (IL)­4 and IL­10 expression was both downregulated, and tumor necrosis factor (TNF)­α and interferon (IFN)­Î³ expression was significantly upregulated. When adding fludarabine or injecting with the traditional Chinese medicine Xuebijing, IL­4 and IL­10 expression was both significantly upregulated, and TNF­α and IFN­Î³ expression was significantly downregulated. When adding fludarabine and downregulating SOCS1, IL­4, IL­10, TNF­α and IFN­Î³ expression presented no significant changes. The above results indicated that, when SOCS1 expression is downregulated, it will activate the JAK1/STAT1 pathway, and thereby promote the polarization of macrophages into M1 type. The findings are of great importance for understanding occurrence, development and treatment of various immune­related diseases.


Assuntos
Janus Quinase 1/imunologia , Macrófagos Peritoneais/imunologia , Fator de Transcrição STAT1/imunologia , Transdução de Sinais/imunologia , Proteína 1 Supressora da Sinalização de Citocina/imunologia , Animais , Anti-Inflamatórios/farmacologia , Diferenciação Celular , Medicamentos de Ervas Chinesas/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Janus Quinase 1/genética , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Fosforilação , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/imunologia , Fator de Transcrição STAT1/agonistas , Fator de Transcrição STAT1/genética , Proteína 1 Supressora da Sinalização de Citocina/antagonistas & inibidores , Proteína 1 Supressora da Sinalização de Citocina/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Vidarabina/análogos & derivados , Vidarabina/antagonistas & inibidores , Vidarabina/farmacologia
19.
Drug Des Devel Ther ; 11: 1663-1671, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652704

RESUMO

Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein. In addition, the production of proinflammatory cytokines, including IL-6, IL-1ß, and tumor necrosis factor-α, were significantly reduced in lipopolysaccharide (LPS)-induced RAW264.7 macrophages treated with rhein. Parallel to the inhibition of proinflammatory cytokines, rhein significantly reduced phosphorylation levels of NF-κB p65 and inducible nitric oxide synthase, as well as COX-2 protein expression levels. Furthermore, rhein significantly reduced NALP3 and cleaved IL-1ß expression in LPS + ATP-induced RAW264.7 macrophages. Thus, the present study demonstrates that rhein may exhibit its anti-inflammatory action via inhibition of NF-κB and NALP3 inflammasome pathways.


Assuntos
Antraquinonas/farmacologia , Anti-Inflamatórios/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamação/prevenção & controle , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Animais Geneticamente Modificados , Movimento Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Inflamassomos/imunologia , Inflamassomos/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Peixe-Zebra/genética
20.
J Cell Biochem ; 118(12): 4230-4239, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28419526

RESUMO

Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti-inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS-induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-ß1 expression; inhibited TNF-α and iNOS expression; and blocked the effect of LPS-promoted TNF-α and iNOS expression. Furthermore, adoptive transfer of ex vivo programed M2 macrophages significantly increased the survival rate of septic mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played the same role as worm infection but had no impact on M1 macrophages. SEA reduced LPS-induced TNF-α and iNOS expression, decreased the inhibitory effect of LPS on IL-10 and TGF-ß1 expression, increased STAT6 phosphorylation, and up-regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be reduced. Therefore, worm infection has a protective effect in septic mice in which SEA may play a key role via the STAT6 and PI3K pathways. This finding may provide a favorable solution for the treatment of sepsis, especially early cases. J. Cell. Biochem. 118: 4230-4239, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Antígenos de Helmintos/imunologia , Citocinas , Macrófagos/metabolismo , Esquistossomose Japônica/complicações , Sepse/complicações , Transdução de Sinais , Animais , Macrófagos/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Transcrição STAT6/metabolismo , Esquistossomose Japônica/imunologia , Esquistossomose Japônica/metabolismo , Sepse/mortalidade , Taxa de Sobrevida
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