Exosomes (Exos) are involved in the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on heart failure (HF). We investigated the molecular mechanisms underlying the involvement of ...BMSC-Exos in ferroptosis on HF.
A rat model of HF and cellular model of hypoxia were established. BMSC-Exos were injected into model rats or co-cultured with model cells. In model rats, the cardiac function (echocardiography), oxidative stress (commercial kits), pathological damage (HE staining), fibrosis (MASSON staining), iron deposition (Prussian blue staining), and cell apoptosis (TUNEL staining) were examined. Viability (cell counting kit-8; CCK-8), cell cycle (flow cytometry), oxidative stress, and Fe
levels were detected in the model cells. GAS5, UL3, YAP, and TAZ expression were detected using qRT-PCR, western blotting, and immunohistochemistry analyses.
BMSC-Exos restored cardiac function and inhibited oxidative stress, apoptosis, pathological damage, fibrosis, and iron deposition in myocardial tissues of HF rats. In hypoxic cells, BMSC-Exos increased cell viability, decreased the number of G1 phase cells, decreased Fe
levels, and inhibited oxidative stress. Ferrostatin-1 (a ferroptosis inhibitor) exhibited a synergistic effect with BMSC-Exos. Additionally, GAS5 was upregulated in BMSC-Exos, further upregulating its target UL3 and Hippo pathway effectors (YAP and TAZ). The relieving effects of BMSC-Exos on HF or hypoxia-induced injury were enhanced by GAS5 overexpression, but weakened by UL3 silencing or verteporfin (a YAP inhibitor).
GAS5-harbouring BMSC-Exos inhibited ferroptosis by regulating the UL3/Hippo pathway, contributing to HF remission in vivo and in vitro.
Our previous study has demonstrated that miR-23b enhances oxidized low-density lipoprotein (oxLDL)-induced inflammatory response of macrophages through the A20/NF-κB signaling pathway, thus ...contributing to atherosclerosis. This study aims to further investigate the upstream regulators of miR-23b in mediating oxLDL-induced inflammatory response. Human monocyte cell line THP1 was induced to differentiate into macrophages followed by the oxLDL stimulation of inflammatory response. The expression of miR-23b, LINC01140, and p53 mRNA was detected by quantitative PCR. The combination of miR-23b and LINC01140 was confirmed by luciferase reporter assay and RNA immunoprecipitation. The binding of p53 and LINC01140 promoter was determined by luciferase reporter assay. The level of inflammatory cytokines, including MCP-1, TNF-α, and IL-1β, was assessed by enzyme-linked immunosorbent assay. LINC01140 was downregulated, while p53 and miR-23b were upregulated in oxLDL-induced inflammatory response of macrophages. Overexpression of LINC01140 reduced NF-κB activity by reducing miR-23b and increasing A20. The transcription of LINC01140 was inhibited by binding of p53 and the LINC01140 promoter region. Knockdown of p53 significantly reduced NF-κB activity and level of inflammatory cytokines by promoting LINC01140 expression. Our findings demonstrated that LINC01140 acts as an anti-inflammatory factor through negatively regulating miR-23/A20 axis. In addition, p53 is identified as a transcriptional repressor of LINC01140.
Objective
This study aimed to investigate the role of long noncoding RNA (LncRNA) myocardial infarction-associated transcript (MIAT) in a heart failure (HF) model in vivo and in vitro by regulating ...the PI3K/Akt signaling pathway.
Methods
We established HF models in vivo and in vitro and evaluated the collagen content of these models and other factors.
Results
We found that when LncRNA MIAT was silenced, vascular endothelial growth factor, phosphorylated protein kinase B (Akt), and phosphorylated phosphoinositide 3-kinase (PI3K) mRNA and protein levels were significantly downregulated, which suggested that MIAT activated the PI3K/Akt signaling pathway. Akt and PI3K expression was not significantly changed. We also found that when LncRNA MIAT was silenced, collagen expression was significantly downregulated. This finding suggested that MIAT promoted myocardial fibrosis during the development of HF. The levels of inflammatory factors were also significantly reduced with silencing of LncRNA MIAT. This finding suggested that MIAT promoted the expression of inflammatory factors in myocardial fibrosis by activating the PI3K/Akt signaling pathway.
Conclusion
This study indicates that silencing LncRNA MIAT may improve myocardial fibrosis and alleviate HF through the PI3K/Akt signaling pathway, which may be helpful for patients with HF to obtain a better therapeutic effect.
Mesenchymal stem cells-derived exosomes (MSCs-exosomes) reportedly possess cardioprotective effects. This study investigated the therapeutic potential and mechanisms of MSCs-exosomes on heart failure ...(HF). H9c2 cells were used to establish a cardiomyocyte hypertrophy model by angiotensin II (Ang II) treatment. Isolated MSCs-exosomes were identified by transmission electron microscope and CD63 detection. Apoptosis rate was measured by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. Levels of inflammatory factors interleukin (IL)-1β, IL-4, IL-6, and tumor necrosis factor (TNF)-α and brain natriuretic peptide (BNP) were determined by ELISA. Expression of apoptosis-related proteins Bax, B-cell lymphoma-2 (Bcl-2), and caspase 3 and Hippo-Yes-associated protein (YAP) pathway-related proteins YAP, phosphor (p)-YAP, and tafazzin (TAZ) was detected by western blotting. Cardiomyocyte hypertrophy of H9c2 cells induced by Ang II was ameliorated by MSCs-exosomes treatment. MSCs-exosomes downregulated Bax and caspase 3 levels and upregulated Bcl-2 level in Ang II-induced H9c2 cells. MSCs-exosomes also reduced the levels of BNP, IL-1β, IL-4, IL-6, and TNF-α in Ang II-induced H9c2 cells. Meanwhile, p-YAP was downregulated and TAZ was upregulated after MSCs-exosomes administration. In conclusion, MSCs-exosomes alleviate the apoptosis and inflammatory response of cardiomyocyte via deactivating Hippo-YAP pathway in HF.
Objective:
Exploring the effectiveness of miR-30b-5p-loaded PEG-PLGA nanoparticles (NPs) for the treatment of heart failure and the underlying mechanism.
Methods:
PEG-PLGA characteristics with ...different loading amounts were first examined to determine the loading, encapsulation, and release of miR-30b-5p from NPs. The effects of miR-30b-5p NPs on cardiac function and structure were assessed by immunofluorescence, echocardiography, HE/Masson staining, and TUNEL staining. The effects of NPs on the expression of factors related to cardiac hypertrophy and inflammation were examined by RT-PCR and western blotting, and the mechanism of miR-30b-5p treatment on heart failure was explored by dual luciferase reporter assay and RT-PCR.
Results:
The size of PEG-PLGA NPs with different loading amounts ranged from 200 to 300 nm, and the zeta potential of PEG-PLGA NPs was negative. The mean entrapment efficiency of the NPs for miR-30b-5p was high (81.8 ± 2.1%), and the release rate reached 5 days with more than 90% release. Distribution experiments showed that NPs were mainly distributed in the heart and had a protective effect on myocardial injury and cardiac function. Compared with a rat model of cardiac failure and miR-30b-5p-non-loaede NP groups, the expression of cardiac hypertrophy markers (ANP, BNPβ-MHC) and inflammatory factors (IL-1β, IL-6) were significantly decreased. Dual luciferase reporter assay assays indicated that miR-30b-5p exerted its effects mainly by targeting TGFBR2.
Conclusion:
PEG-PLGA NPs loaded with miR-30b-5p improved cardiac function, attenuated myocardial injury, and regulated the expression of factors associated with cardiac hypertrophy and inflammation by targeting TGFBR2.
In order to obtain desirable crop yields, grain seeds need to be sown at the optimal seed amount per hectare with uniform distribution in the field. In previous grain sowing processes, the seeding ...rates are controlled by the rotational speed of the flute roller which significantly effects the uniform distribution of the seeds due to disturbances, such as the reduction of the seeds' mass in the hopper and the change of working length of the flute roller. In order to overcome the above problem, we developed an adaptive roller speed control system based on the seed flow rate sensor. The developed system can monitor and feedback actual seeding rates. In addition, based on the monitoring value of the real-time seeding rates, an adaptive roller speed control method (ARSCM), which contains an algorithm for calculating the seeding rate with a compensation, was proposed. Besides, the seeding performance of the ARSCM and that of the conventional roller speed control method (CRSCM) were compared. The results of constant-velocity experiments demonstrated that the accuracy (SA) and the coefficient of variation (SCV) of the seeding rates controlled by the ARSCM were 94.12% and 6.77%, respectively. As for the CRSCM, the SA and SCV were 89.00% and 8.95%, respectively. Under variable-velocity conditions, the SA and SCV of the proposed system were 91.58% and 11.08%, respectively, while those of the CRSCM were 88.48% and 13.08%, respectively. Based on the above results, this study concluded that the ARSCM is able to replace the CRSCM in practical sowing processes for the optimal and uniform seed distribution in the field.
Hypertension is the most common chronic disease, and most important risk factor for cardiovascular disease. This meta-analysis aimed to explore the association between hepatic lipase gene (LIPC) gene ...-250G/A (rs2070895) and -514C/T (rs1800588) polymorphisms and the susceptibility to hypertension.
Published studies were searched using the PubMed, Embase and Cochrane Library databases. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Sensitivity analysis was performed using "leave one out" method. Egger's test was used to evaluate the publication bias. The random effect model was used to calculate the pooled effect size if P < 0.05 or I
≥ 50%; otherwise, the fixed effect model was selected.
Four eligible studies, including 2599 participants, were enrolled in the included studies from 2007 to 2014. Quality evaluation revealed that each study had high NOS scores ranged from 5 to 7. The LIPC rs1800588 polymorphism was not found to be associated with the susceptibility to hypertension under all genetic models (T vs C, P = 0.38; CT vs CC, P = 0.46; TT vs CC, P = 0.38; TT vs CC + CT, P = 0.54; TT + CT vs CC, P = 0.34). Notably, the frequencies of the AA+GA genotypes of LIPC rs2070895 polymorphism were related to an increased risk of hypertension (AA+GA vs. GG, OR = 1.1954, 95% CI: 1.0001-1.4288, P = 0.05).
The LIPC rs2070895 polymorphism was found to be related to an increased risk of hypertension. However, LIPC rs1800588 polymorphism was not associated with the susceptibility to hypertension.
We aimed to comprehensively evaluate the curative effect of torasemide, tolvaptan, furosemide and azosemide on patients with heart failure.
Relevant studies were retrieved by searching the electronic ...databases until May 2018. Quality assessment and data extraction of selected studies were evaluated by two reviewers. Heterogeneity across studies was assessed utilizing the I2 statistic and Q- test, and appropriate effect model was selected to calculate the pooled effect size. Network meta-analysis was conducted and the convergence degree of model was evaluated.
A total of 12 studies were enrolled in this study. Significant heterogeneity was not identified across the studies. Significantly greater differences were found in left ventricular ejection fraction (LVEF) for furosemide VS. azosemide, in brain natriuretic peptide (BNP) for furosemide VS. azosemide and furosemide VS. torasemide, and in adverse effects for furosemide VS. torasemide through Meta-analysis of direct comparison. In addition, network meta-analysis results suggested there were no significant differences in adverse effects, mortality, BNP and LVEF among these groups. However, the relatively low mortality and small improvement of BNP and LVEF were found in HF patients treated with torasemide.
Torasemide might be an optimal treatment for HF patients considering its comprehensive curative effect.
Bone cancer pain (BCP) is the most common type of pain in cancer patients, during which microglia cells were activated. A previous study showed BAM8-22 had the ability to alleviate BCP via inhibiting ...microglia activation while the mechanism was not clear. This study aims to investigate the specific mechanism of BAM8-22 inhibiting microglia activation. This study was mainly investigated in BCP mice or LPS-treated microglia BV-2 cells. The behavior tests of mice were performed at 0, 1, 2, 12, and 24 h after BAM8-22 treatment. The expression of miR-184 and CX3CR1 mRNAs was detected by quantitative RT-PCR. The expression of CX3CR1 protein and microglia activation marker, Iba-1, was measured by western blot analysis. The levels of TNF-α and IL-1β were detected by ELISA. Dual-luciferase assay was performed to verify the combination between miR-184 and CX3CR1. After BAM8-22 treatment, increased miR-184 level was observed in both BCP mice and LPS-treated BV-2 cells, with the downregulated expression of Iba-1 and inflammatory cytokines, namely the inhibition of microglia activation. The inhibition of miR-184 reversed the inhibitory effect of BAM8-22 on microglia activation. Further, in vitro studies showed that miR-184 bound to the 3′UTR of CX3CR1 and inhibited microglia activation via repressing CX3CR1 expression. What’s more, the suppression of CX3CR1 expression eliminated the reversal effect of the miR-184 inhibitor on BAM8-22-induced microglia activation and decreased Iba-1 expression and pro-inflammatory cytokine secretion. In BCP models, miR-184 was upregulated by BAM8-22 and the elevated level of miR-184 bound to the 3′UTR region of CX3CR1 and repressed CX3CR1 expression, thus inhibiting the microglia activation, suggesting the potential application of miR-184/CX3CR1 for BCP treatment.
Atrial fibrillation (AF) is the most common persistent cardiac arrhythmia. This study aimed to estimate its prevalence and explore associated factors in adults aged 18 years or older in China.
Study ...data were derived from a national sample from July 2020 to September 2021. Participants were recruited using a multistage stratified sampling method from twenty-two provinces, autonomous regions, and municipalities in China. AF was determined based on a history of diagnosed AF or electrocardiogram results.
A total of 114,039 respondents were included in the final analysis with a mean age of 55 years (standard deviation 17), 52·1% of whom were women. The crude prevalence of AF was 2·3% (95% confidence interval CI 1·7-2·8) and increased with age. The age-standardized AF prevalence was 1·6% (95% CI 1·6-1·7%) overall, and 1·7% (1·6-1·8%), 1·4% (1·3-1·5%), 1·6% (95% CI 1·5-1·7%), and 1·7% (1·6-1·9%) in men, women, urban areas, and rural areas, respectively. The prevalence was higher in the central regions (2·5%, 2·3-2·7%) than in the western regions (1·5%, 1·0-2·0%) and eastern regions (1·1%, 1·0-1·2%) in the overall population, either in the gender or residency subgroups. The associated factors for AF included age (per 10 years; odds ratio 1·41 95% CI 1·38-1·46; p < 0·001), men (1·34 1·24-1·45; p < 0·001), hypertension (1·22 1·12-1·33; p < 0·001), coronary heart disease (1·44 1·28-1·62; p < 0·001), chronic heart failure (3·70 3·22-4·26; p < 0·001), valvular heart disease (2·13 1·72-2·63; p < 0·001), and transient ischaemic attack/stroke (1·22 1·04-1·43; p = 0·013).
The prevalence of AF was 1.6% in the Chinese adult population and increased with age, with significant geographic variation. Older age, male sex, and cardiovascular disease were potent factors associated with AF. It is crucial to increase the awareness of AF and disseminate standardized treatment in clinical settings to reduce the disease burden.
This research was supported the Nature Science Foundation of Hubei province (No: 2017CFB204).
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