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1.
Artigo em Inglês | MEDLINE | ID: mdl-38614212

RESUMO

OBJECTIVE: Limited evidence exists regarding the efficacy of preoperative exercise in reducing short-term complications after minimally invasive surgery in patients with non-small cell lung cancer. This study aims to investigate the impact of preoperative exercise on short-term complications after minimally invasive lung resection. METHODS: In this prospective, open-label, randomized (1:1) controlled trial at Xiangya Hospital, China (September 2020 to February 2022), patients were randomly assigned to a preoperative exercise group with 16-day alternate supervised exercise or a control group. The primary outcome assessed was short-term postoperative complications, with a follow-up period of 30 days postsurgery. RESULTS: A total of 124 patients were recruited (preoperative exercise group n = 62; control n = 62). Finally, 101 patients (preoperative exercise group; n = 51 and control; n = 50) with a median age of 56 years (interquartile range, 50-62 years) completed the study. Compared with the control group, the preoperative exercise group showed fewer postoperative complications (preoperative exercise 3/51 vs control 10/50; odds ratio, 0.17; 95% CI, 0.04-0.86; P = .03) and shorter hospital stays (mean difference, -2; 95% CI, -3 to -1; P = .01). Preoperative exercise significantly improved depression, stress, functional capacity, and quality of life (all P < .05) before surgery. Furthermore, preoperative exercise demonstrated a significantly lower minimum blood pressure during surgery and lower increases in body temperature on day 2 after surgery, neutrophil-to-lymphocyte ratio, and neutrophil count after surgery (all P < .05). Exploratory research on lung tissue RNA sequencing (5 in each group) showed downregulation of the tumor necrosis factor signaling pathway in the preoperative exercise group compared with the control group. CONCLUSIONS: Preoperative exercise training decreased short-term postoperative complications in patients with non-small cell lung cancer.

2.
Front Endocrinol (Lausanne) ; 14: 1035029, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027164

RESUMO

Objective: Diabetes pathology relies on exosomes (Exos). This study investigated how peripheral blood Exo-containing microRNAs (miRNAs) cause vascular injury in type 2 diabetes (T2D). Methods: We removed DEmiRNA from T2D chip data from the GEO database. We isolated Exo from 15 peripheral blood samples from T2D patients and 15 healthy controls and measured Exo DEmiRNA levels. We employed the intersection of Geneards and mirWALK database queries to find T2D peripheral blood mRNA-related chip target genes. Next, we created a STRING database candidate target gene interaction network map. Next, we performed GO and KEGG enrichment analysis on T2D-related potential target genes using the ClusterProfiler R package. Finally, we selected T2D vascular damage core genes and signaling pathways using GSEA and PPI analysis. Finally, we used HEK293 cells for luciferase assays, co-cultured T2D peripheral blood-derived Exo with HVSMC, and detected HVSMC movement alterations. Results: We found 12 T2D-related DEmiRNAs in GEO. T2D patient-derived peripheral blood Exo exhibited significantly up-regulated miR-135a-3p by qRT-PCR. Next, we projected miR-135a-3p's downstream target mRNA and screened 715 DEmRNAs to create a regulatory network diagram. DEmRNAs regulated biological enzyme activity and vascular endothelial cells according to GO function and KEGG pathway analysis. ErbB signaling pathway differences stood out. PPI network study demonstrated that DEmRNA ATM genes regulate the ErbB signaling pathway. The luciferase experiment validated miR-135a-3p and ATM target-binding. Co-culture of T2D patient-derived peripheral blood Exo with HVSMC cells increases HVSMC migration, ErbB2, Bcl-2, and VEGF production, and decreases BAX and ATM. However, miR-135a-3p can reverse the production of the aforesaid functional proteins and impair HVSMC cell movement. Conclusion: T2D patient-derived peripheral blood Exo carrying miR-135a-3p enter HVSMC, possibly targeting and inhibiting ATM, activating the ErbB signaling pathway, promoting abnormal HVSMC proliferation and migration, and aggravating vascular damage.


Assuntos
Diabetes Mellitus Tipo 2 , Exossomos , MicroRNAs , Lesões do Sistema Vascular , Humanos , Células Endoteliais/metabolismo , Exossomos/genética , Exossomos/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia , Células HEK293 , MicroRNAs/genética , MicroRNAs/metabolismo , Luciferases/metabolismo , RNA Mensageiro/metabolismo
3.
Mol Med ; 29(1): 130, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740187

RESUMO

BACKGROUND: It has been documented that aerobic exercise (AE) has a positive effect on improving cognitive function in type 2 diabetes (T2DM) patients. Here, we tried to explore how AE regulates the expression of long non-coding RNA in serum-exosomes (Exos), thereby affecting cognitive impairment in T2DM mice as well as its potential molecular mechanism. METHODS: T2DM mouse models were constructed, and serum-Exos were isolated for whole transcriptome sequencing to screen differentially expressed lncRNA and mRNA, followed by prediction of downstream target genes. The binding ability of miR-382-3p with a long non-coding RNA MALAT1 and brain-derived neurotrophic factor (BDNF) was explored. Then, primary mouse hippocampal neurons were collected for in vitro mechanism verification, as evidenced by the detection of hippocampal neurons' vitality, proliferation, and apoptosis capabilities, and insulin resistance. Finally, in vivo mechanism verification was performed to assess the effect of AE on insulin resistance and cognitive disorder. RESULTS: Transcriptome sequencing analysis showed that MALAT1 was lowly expressed and miR-382-3p was highly expressed in serum-Exos samples of T2DM mice. There were targeted binding sites between MALAT1 and miR-382-3p and between miR-382-3p and BDNF. In vitro experiments showed that MALAT1 upregulated BDNF expression by inhibiting miR-382-3p. Silencing MALAT1 or overexpressing miR-382-3p could reduce the expression of INSR, IRS-1, IRS-2, PI3K/AKT, and Ras/MAPK, inhibit neuronal proliferation, and promote apoptosis. In vivo experiments further confirmed that AE could increase the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thereby improving cognitive impairment in T2DM mice. CONCLUSION: AE may upregulate the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thus improving cognitive impairment in T2DM mice.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Exossomos , Resistência à Insulina , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Fator Neurotrófico Derivado do Encéfalo/genética , Disfunção Cognitiva/genética , Disfunção Cognitiva/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Resistência à Insulina/genética , MicroRNAs/genética , Fosfatidilinositol 3-Quinases , RNA Longo não Codificante/genética , Transdução de Sinais
4.
J Diabetes Res ; 2023: 3720602, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937538

RESUMO

This research is aimed at figuring out the potential circular RNA (circRNA)/long noncoding RNA- (lncRNA-) microRNA- (miRNA-) mRNA regulatory networks associated with a vascular injury in type 2 diabetes mellitus (T2DM). Differentially expressed genes (DEGs) screened in T2DM-related expression datasets were intersected with genes associated with vascular injury in T2DM to obtain candidate DEGs, followed by the construction of an interaction network of DEGs. The upstream miRNAs of candidate genes were predicted by mirDIP, miRWalk, and DIANA TOOLS databases, and the upstream lncRNAs/circRNAs of miRNAs by DIANA-LncBase/circBank database, followed by the construction of circRNA/lncRNA-miRNA-mRNA regulatory networks. Peripheral blood was attained from T2DM patients with macroangiopathy for clinical validation of expression and correlation of key factors. Differential analysis screened 37 candidate DEGs correlated with vascular injury in T2DM. Besides, MAPK3 was a core gene associated with vascular injury in T2DM. Among the predicted upstream miRNAs of MAPK3, miR-4270, miR-92a-2-5p, miR-423-5p, and miR-613 ranked at the top according to binding scores. The upstream lncRNAs and circRNAs of the 4 miRNAs were further predicted, obtaining 11 candidate lncRNAs and 3 candidate circRNAs. Moreover, KCNQ1OT1, circ_0020316, and MAPK3 were upregulated, but miR-92a-2-5p was downregulated in the peripheral blood of T2DM patients with macroangiopathy. Mechanistically, KCNQ1OT1 and circ_0020316 bound to miR-92a-2-5p that inversely targeted MAPK3. Collectively, KCNQ1OT1/circ_0020316-miR-92a-2-5p-MAPK3 coexpression regulatory networks might promote vascular injury in T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , MicroRNAs , RNA Longo não Codificante , Lesões do Sistema Vascular , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Redes Reguladoras de Genes , Análise em Microsséries
5.
Diabetes Res Clin Pract ; 197: 110261, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36681355

RESUMO

AIM: The regulatory mechanism of m6A regulators in vascular endothelial function of type 2 diabetes mellitus (T2DM) remains largely unknown. We addressed this issue based on the data retrieved Gene Expression Omnibus (GEO) database and experimental validations. METHODS: Expression of m6A methylation regulators was evaluated in T2DM samples of GSE76894 dataset and GSE156341 dataset. Further analysis of candidate m6A methylation regulators was conducted in the thoracic aorta of db/db mice and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). Ectopic expression and depletion experiments were conducted to detect effects of m6A methylation regulators on vascular endothelial function in T2DM. RESULTS: It emerged that three m6A methylation regulators (HNRNPC, RBM15B, and ZC3H13) were highly expressed in T2DM, which were related to vascular EC function, showing diagnostic values for T2DM. HNRNPC expression in the thoracic aorta of db/db mice was higher than that in heterozygous db mice, and HNRNPC expression in HG-induced HUVECs was upregulated when compared with normal glucose-exposed HUVECs. Furthermore, HNRNPC activated PSEN1-dependent Notch pathway to induce eNOS inactivation and NO production decrease, thereby causing vascular endothelial dysfunction in T2DM. CONCLUSIONS: HNRNPC impaired vascular endothelial function to enhance the development of vascular complications in T2DM through PSEN1-mediated Notch signaling pathway.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Vasculares , Animais , Humanos , Camundongos , Adenosina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Glucose/farmacologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Metilação , Presenilina-1/metabolismo , RNA/metabolismo
6.
Diabetes Res Clin Pract ; 195: 110176, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36427628

RESUMO

AIMS: Insulin resistance (IR) is a critical marker underlying type 2 diabetes mellitus (T2DM). Exercise is reported to prevent IR, yet the mechanism of which is complicated and largely unknown. Here, the study aimed to ascertain whether and how aerobic exercise mediates IR in T2DM. METHODS: An in vivo model of high-fat diet (HFD)-induced IR and an in vitro model of high-glucose-induced IR were constructed. RESULTS: Aerobic exercise training in mice led to attenuation of IR in the vascular endothelium. microRNA-299-5p (miR-299-5p) expression was deficient in T2MD, which could be restored by aerobic exercise through modulating the DNA methylation modification enzymes. The expression of miR-299-5p enhanced by aerobic exercise consequently resulted in ameliorating the IR in vivo. Furthermore, increased levels of nitric oxide (NO), reduced levels of Angiotensin II (Ang II), vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in response to miR-299-5p elevation suggested the anti-IR role of miR-299-5p in IR-cell model. Dual-luciferase reporter and ChIP assays identified that miR-299-5p could bind to resistin and hence repressed the resistin level. CONCLUSION: The key observation of the study is that aerobic exercise stimulates miR-299-5p-targeted resistin inhibition through demethylation, which underlies the mechanism of reducing IR.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , MicroRNAs , Camundongos , Animais , Resistência à Insulina/genética , MicroRNAs/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/metabolismo , Resistina/genética , Resistina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Endotélio Vascular/metabolismo , Desmetilação
7.
Front Public Health ; 10: 909766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968455

RESUMO

Introduction: Our previous studies showed that Xiangya Hospital Circuit Training (X-CircuiT) effectively improved physical fitness and reversed pre-frailty in community-dwelling older adults. This study aimed to explore the generalizability and applicability of X-CircuiT in different aged populations in the context of exercise intensity and energy expenditure. Methods: We prospectively recruited 72 community-dwelling sedentary adults, twelve adults divided into 6 age groups ranging from 20 to 80 years old and separated by decades. Cardiopulmonary exercise testing was performed to determine peak heart rate (HRpeak). An individual HR-oxygen consumption regression equation was fit for each participant, and then a session of remote heart rate monitored X-CircuiT was performed. Exercise intensity (%HRpeak) and energy expenditure of X-CircuiT among the six age groups were assessed. Further sub-analysis was conducted by dividing the participants by peak metabolic equivalent (MET) values, <5 METs, 5-7 METs, and more than 7METs to explore the relationship between maximum exercise capacity and exercise intensity of X-CircuiT. Results: The average %HRpeak of X-CircuiT for subjects in the 20-29, 30-39, 40-49, 50-59, 60-69, and 70-80 age groups were 54 ± 6, 59 ± 8, 60 ± 8, 62 ± 5, 66 ± 10, and 67 ± 13, respectively (p = 0.008); and the average energy expenditure was 121.9 ± 26.5, 123.3 ± 33.8, 129.2 ± 40.9, 130.9 ± 31.8, 146.8 ± 29.0, and 125.0 ± 28.4 kcal, respectively. The average %HRpeak for the warm-up, aerobic, acupoint patting, resistance, and stretching stages in overall subjects was 61 ± 9, 70 ± 10, 70 ± 10, 63 ± 9, and 57 ± 9, respectively. Furthermore, when subjects were divided by peak METs, it was found that the lower the peak METs, the greater the value of the relative exercise intensity indicators. The aerobic and acupoint stages of X-CircuiT could illicit a response of high intensity for those with peak METs <5, moderate intensity in those with peak METs of 5-7, and low-intensity for those with peak METs of more than 7. Conclusion: Xiangya Hospital Circuit Training followed the principle of low-intensity warm-up and medium-intensity training with multicomponent exercise training. It is classified as a moderate-intensity exercise for sedentary middle-aged and older adults, or those with a maximum exercise capacity of 5-7 METs, and is classified as a low-intensity exercise for young people.


Assuntos
Exercícios em Circuitos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Hospitais , Humanos , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Adulto Jovem
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(11): 1260-1266, 2021 Nov 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34911861

RESUMO

OBJECTIVES: Patients with cervical cancer who have received radiotherapy often suffer from systemic muscle volume reduction and quality of life decline due to systemic effects of tumor and side effects of radiotherapy. The purpose of this study was to investigate the status of muscle fitness, quality of life, and psychological pain in patients with cervical cancer who received radiotherapy, and to explore the correlation between muscle fitness, quality of life, and psychological pain. METHODS: A total of 202 cervical cancer patients aged 19-71, who received radiotherapy in Hunan Cancer Hospital from July 2020 to February 2021, were selected by convenience sampling method. Functional Assessment of Cancer Therapy Cervix (FACT-CX) and Distress Thermometer (DT) were used for the survey. The patient's grip strength was assessed by a handgrip meter and compared with that of healthy Chinese women of the same age. The correlation between muscle fitness and quality of life and psychological pain was analyzed. RESULTS: The grip strength of cervical cancer patients receiving radiotherapy was significantly lower than that of healthy Chinese women at the same age (P<0.05). Multiple linear regression analysis showed that there were 4 factors affecting grip strength, including emotional thermometer score, social and family status score, cervical cancer related function score and tumor metastasis (all P<0.05). CONCLUSIONS: The grip strength of patients with cervical cancer undergoing radiotherapy is generally decreased, which is affected by many factors, and is closely related to the quality of life and psychological pain of patients. In the future, dynamic attention should be paid to the changes of grip strength and related functions in patients receiving radiotherapy for cervical cancer, the potential risks in the treatment should be identified early, and targeted intervention should be taken.


Assuntos
Angústia Psicológica , Neoplasias do Colo do Útero , Ansiedade , Feminino , Força da Mão , Humanos , Qualidade de Vida , Neoplasias do Colo do Útero/radioterapia
9.
Front Cardiovasc Med ; 8: 638682, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33634176

RESUMO

This 18-year cross-sectional study was conducted to provide data on the safety of exercise testing in the clinical Chinese population. We retrospectively identified exercise tests completed at Xiangya Hospital of Central South University from January 1, 2002 to December 31, 2019. From 43,130 unique individuals (50.9% female), a total of consecutive 50,142 tests (standard exercise testing 29,466; cardiopulmonary exercise testing 20,696) were retrieved. Demographics, patients' medical history, exercise testing characteristics, and exercise testing-related adverse events were described. Safety data is expressed as the number of adverse events per 10,000 tests, with 95% confidence interval. The average patients' age was 51 ± 13 years. The majority of patients were diagnosed with at least one disease (N = 44,941, 89.6%). Tests were maximal or symptom-limited. Common clinical symptoms included dizziness (6,822, 13.6%), chest pain or distress (2,760, 5.5%), and musculoskeletal limitations (2,507, 5.0%). Out of 50,142 tests, three adverse events occurred, including one sustained ventricular tachycardia, one sinus arrest with junctional escape rhythm at a rate of 28 bpm, and one syncopal event with fecal and urinary incontinence. The rate of adverse events was 0.8 events per 10,000 tests (95% confidence interval, 0.2-3.0) in men, 0.4 per 10,000 tests (0.7-2.2) in women, and 0.6 per 10,000 tests (0.21.8) total. This study represents the largest dataset analysis of exercise testing in the clinical Chinese population. Our results demonstrate that clinical exercise testing is safe, and the low rate of adverse events related to exercise testing might be due to the overall changes in clinical practice over time.

10.
Life Sci ; 265: 118757, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33197444

RESUMO

AIM: Recent evidence has suggested the important implications of microRNAs (miRNAs) in the processes of proliferation and tissue remodeling in endometriosis (EMS). We therefore aim to determine the role of miR-202-3p in the pathophysiology of EMS and its underlying mechanisms. METHODS: Experimental endometriosis was induced in ovariectomized mice implanted with a slow-release 17-ß estradiol capsule. Eutopic endometrial stromal cells (euESCs) were isolated and assayed for proliferative, invasive and apoptotic properties by EdU staining, Transwell assays, and flow cytometry. The invasive and apoptotic features in the endometrium of mice with EMS in vivo were evaluated by using immunohistochemical staining and TUNEL assays. RESULTS: miR-202-3p was observed to be downregulated in the endometrial tissues of EMS patients. MiR-202-3p was also found to target YAP1 which resulted in reduced euESC proliferation and invasion and increased apoptosis. YAP1 was able to phosphorylated STAT3 which consequently upregulated S100A6 to promote the proliferative and invasive abilities of euESCs. MiR-202-3p was thereby proposed to act as an inhibitor of proliferation and tissue damage in the in vivo setting of EMS, its effects however, were able to be counteracted byS100A6, which reversed the effects of miR-202-3p on tissue injury and cell proliferation. CONCLUSION: Our data together evidenced that miR-202-3p targeted YAP1 to reduce STAT3-mediated S100A6 whereby preventing the progression of EMS.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Endometriose/metabolismo , MicroRNAs/metabolismo , Proteína A6 Ligante de Cálcio S100/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica , Marcação In Situ das Extremidades Cortadas , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Proteínas de Sinalização YAP
11.
Am J Physiol Cell Physiol ; 319(3): C579-C588, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32608990

RESUMO

Identification of specific biomarkers for ischemic stroke is necessary due to their abilities to improve treatment outcomes. Many studies have demonstrated the involvement of microRNAs (miRNAs) in the pathogenesis and complications of ischemic stroke and patient outcomes. We found that the expression of miR-874-3p was downregulated in clinical samples of ischemic stroke. Thus the present study explored the potential role of miR-874-3p in ischemic stroke and related mechanisms. A mouse model of ischemic stroke was constructed by middle cerebral artery occlusion. The relationship among miR-874-3p, C-X-C motif chemokine ligand 12 (CXCL12), and the Wnt/ß-catenin pathway was explored by dual luciferase reporter assay and Western blot analysis. Angiogenesis and brain tissue apoptosis were evaluated by immunofluorescence staining and TUNEL staining, respectively. ELISA was introduced to measure levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, IL-8, and IL-10 in brain tissues. Primary hippocampal neuronal cells were isolated from the mouse model of ischemic stroke and incubated with human umbilical vein endothelial cells (HUVECs) for HUVEC tube formation. High expression of CXCL12 and low expression of miR-874-3p were confirmed in ischemic stroke. In addition, miR-874-3p was found to target and downregulate CXCL12, thus reducing TNF-α, IL-1, IL-6, and IL-8 levels, but enhancing IL-10 level. Collectively, upregulating miR-874-3p inhibits CXCL12 expression to promote angiogenesis and inhibit inflammation in ischemic stroke mice by activating the Wnt/ß-catenin pathway, which may provide a new direction of ischemic stroke treatment.


Assuntos
Quimiocina CXCL12/metabolismo , Inflamação/metabolismo , MicroRNAs/genética , Acidente Vascular Cerebral/metabolismo , Animais , Apoptose/fisiologia , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Camundongos , Neurônios/metabolismo , Acidente Vascular Cerebral/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
12.
Mol Ther Nucleic Acids ; 18: 34-44, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31479923

RESUMO

Insulin resistance (IR) is the primary pathological mechanism underlying type 2 diabetes mellitus (T2DM). Here, the study aimed to ascertain whether and how exercise mediates IR in T2DM. An in vivo mouse model of high-fat diet-induced IR and an in vitro high-glucose-induced IR model were constructed. High long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was detected in T2MD and was positively correlated with HOMA-IR and resistin levels. Then, short hairpin RNA targeting MALAT1 (sh-MALAT1) or pcDNA-MALAT1 was delivered into human umbilical vein endothelial cells (HUVECs) to knock down or upregulate its expression, respectively. Silencing of MALAT1 resulted in reduced levels of resistin, Ang II, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1), and p-insulin receptor substrate-1 (p-IRS)/ISR-1, and decreased cell migration, as well as enhanced glucose uptake and levels of nitric oxide (NO) and p-Akt/Akt. In the IR mouse model, exercise was observed to downregulate MALAT1 to reduce resistin, whereby exercise reduced homeostatic model assessment-insulin resistance (HOMA-IR). Besides, exercise also elevated microRNA-382-3p (miR-382-3p) expression in the serum of IR mice. Dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays identified that MALAT1 could bind to miR-382-3p to upregulate resistin. Collectively, the key observations of the study provide evidence that inhibition of MALAT1 elevates miR-382-3p to repress resistin, which consequently underlies the mechanism of exercise protecting against IR, highlighting a direction for T2DM therapy development.

13.
J Cell Physiol ; 234(10): 18653-18665, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31062344

RESUMO

Acute myocardial infarction (AMI), a severe consequence of coronary atherosclerotic heart disease, is often associated with high mortality and morbidity. Emerging evidence have shown that the inhibition of the extracellular-signal-regulated kinase (ERK) signaling pathway appears to protect against AMI. Epiregulin (EREG) is an autocrine growth factor that is believed to activate the MEK/ERK signaling pathway. Therefore, the aim of the present study was to determine the expression patterns of EREG in AMI and to further study its effects on AMI induced experimentally in rats focusing on angiogenesis and left ventricular remodeling. Microarray-based gene expression profiling of AMI was used to identify differentially expressed genes. To understand the biological significance of EREG and whether it is involved in AMI disease through the ERK1/2 signaling pathway, rats after AMI were treated with small interfering RNA (siRNA) against EREG, an ERK1/2 pathway inhibitor, PD98059, or both of them. The microarray data sets GSE66360 and GSE46395 showed that EREG was robustly induced in AMI. Both siRNA-mediated depletion of EREG and PD98059 treatment were shown to significantly increase infarct size and left ventricular cardiomyocyte loss and enhance left ventricular remodeling. In addition, we also found that the ERK1/2 signaling pathway was inhibited following siRNA-mediated EREG inhibition and PD98059 could enhance the effects of EREG inhibition on AMI. In conclusion, these findings highlight that the silencing of EREG inhibits angiogenesis and promotes left ventricular remodeling by disrupting the ERK1/2 signaling pathway, providing a novel therapeutic target for limiting AMI.


Assuntos
Epirregulina/metabolismo , Sistema de Sinalização das MAP Quinases , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica , Remodelação Ventricular , Animais , Diástole/efeitos dos fármacos , Eletrocardiografia , Flavonoides/farmacologia , Testes de Função Cardíaca , Hemodinâmica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Infarto do Miocárdio/patologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Neovascularização Fisiológica/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Ratos Wistar , Sístole/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
14.
J Cardiovasc Transl Res ; 11(6): 450-458, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30232730

RESUMO

Previously, we found that miR-492 delayed the progression of atherosclerosis (AS) by acting as an up-stream regulator of resistin. Therefore, we hypothesized that the anti-atherogenic effects of exercise are related to miR-492-mediated downregulation of resistin and repair of endothelial injury. In this study, we investigated the effects of the miR-492/resistin axis on improving endothelial injury in ApoE-/- mice (ApoE-deficient/knockout in C57BL/6 mice) through swimming exercises. Our results showed that the severity of AS and insulin resistance (IR) in these mice were significantly reduced by swimming exercises. In addition, miR-492 expression in the aortic endothelium of ApoE-/- mice was decreased, in addition to increased levels of resistin. Interestingly, swimming exercises increased miR-492 expression while decreasing that of resistin. Taken together, swimming exercises delayed the progression of AS, possibly by upregulating miR-492 and downregulating resistin in aortic endothelium. Therefore, exercises modulated glucose and lipid metabolism, alleviated endothelial IR, and repaired endothelial injury.


Assuntos
Aorta/metabolismo , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Terapia por Exercício/métodos , Resistência à Insulina , MicroRNAs/metabolismo , Resistina/metabolismo , Animais , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/genética , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Biomarcadores/sangue , Glicemia/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , MicroRNAs/genética , Placa Aterosclerótica , Resistina/genética , Transdução de Sinais , Natação
15.
Exp Ther Med ; 12(3): 1901-1907, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27588108

RESUMO

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.

16.
J Diabetes Investig ; 7(4): 615-21, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27181277

RESUMO

AIMS/INTRODUCTION: Heart rate recovery (HRR) after exercise is considered to be a new index of autonomic dysfunction associated with cardiovascular disease and mortality. The present study aimed to investigate the risk factors of HRR and the effects of exercise on the abnormal HRR in type 2 diabetes. MATERIALS AND METHODS: A total of 123 type 2 diabetes patients were recruited, and the oral glucose tolerance test and exercise test were carried out to analyze the risk factors associated with abnormal HRR. Among these patients, 42 patients with abnormal HRR were further randomized to either the conventional therapy group (CT group; n = 20) or the intensive therapy group (IT group; n = 22). The CT group patients underwent metformin and diet control, whereas the IT group additionally underwent a combined moderate intensity aerobic and resistance training three times per week for 12 weeks. The results of blood sample analysis and HRR were recorded before and after the training. RESULTS: Abnormal HRR was related to fasting blood glucose, glycosylated hemoglobin, low-density lipoprotein cholesterol, and resting and maximum heart rates (P < 0.05 for both). After training, the IT group had significantly lower levels of fasting blood glucose, glycosylated hemoglobin and resting heart rate than the CT group (all P < 0.01 or P < 0.005). Significant improvement in HRR and metabolic equivalents was observed in the IT group compared with the CT group (P < 0.05). CONCLUSIONS: These data suggested that combined aerobic and resistance training improved cardiac autonomic dysfunction as measured by HRR in type 2 diabetes patients. This might be due to better improvement of glycemic control, resting heart rate and physical fitness.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/terapia , Terapia por Exercício , Frequência Cardíaca , Neuropatias Diabéticas/complicações , Teste de Esforço , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
17.
J Phys Ther Sci ; 27(7): 2365-71, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26311110

RESUMO

[Purpose] To investigate the effects of combined aerobic and resistance training on glycolipid metabolism and inflammation levels in type 2 diabetes mellitus patients. [Subjects and Methods] Forty-two diabetes patients were randomized to the conventional therapy group (n = 20) or intensive therapy group (n = 22). The control group contained 20 healthy people. The conventional therapy group received routine drug therapy and diet control, while the intensive therapy group additionally underwent combined aerobic and resistance training for 12 weeks. The oral glucose tolerance test and cardiopulmonary exercise testing were performed. Toll-like receptor 4 and NF-κBp65 protein and mRNA expressions were determined by qPCR and western blotting. ELISA was used to determine the expression levels of interleukin-18, interleukin-33, pentraxin-related protein 3, and human cartilage glycoprotein 39. [Results] After exercise training, the intensive therapy group had significantly lower postprandial blood glucose, postprandial insulin, and glycated hemoglobin level and insulin resistance index than the conventional therapy group. The intensive therapy group had significantly lower toll-like receptor 4 and NF-κBp65 protein and mRNA expressions, and serum interleukin-18 levels but significantly higher serum interleukin-33 levels. [Conclusion] Combined aerobic and resistance training can improve glycolipid metabolism and reduce low-grade inflammation in patients with diabetes mellitus patients.

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