Mechanism of miR-30b-5p-Loaded PEG-PLGA Nanoparticles for Targeted Treatment of Heart Failure

Ren, Yu; Wang, Xiao; Liang, Hongyu; He, Weiyang; Zhao, Xingsheng

doi:10.3389/fphar.2021.745429

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…Due to its good solubility in water and many organic solvents and its non-toxicity, PEG is considered a kind of non-ionic polymer. PEG has been widely used to extract polysaccharides from a variety of plants ( 32 ). As shown in Figure 1A , when the PEG molecular weight was between 2,000 and 6,000, the extraction rate of ALPs increased significantly.…”

Section: Resultsmentioning

confidence: 99%

Extraction, structural characterization, and antioxidant activity of polysaccharides derived from Arctium lappa L.

Gao

Chen

et al. 2023

Front. Nutr.

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IntroductionArctium lappa L. root has high nutritional and medicinal values and has been identified as a healthy food raw material by the Ministry of Health of the People's Republic of China.MethodsIn the present study, an aqueous two-phase system (ATPS) of polyethylene glycol (PEG)-(NH4)2SO4 was used to extract Arctium lappa L. polysaccharides (ALPs) from the Arctium lappa L. roots, the optimal extraction conditions of crude ALPs were optimized by using the single-factor experiment and response surface methodology. The structure and composition of ALPs were determined by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and high-performance liquid chromatography (HPLC). At the same time, the antioxidant activity of ALPs was investigated by in vitro antioxidant experiment.ResultsThe optimized extraction parameters for extraction ALPs were as follows: the PEG relative molecular weight of 6,000, a quality fraction of PEG 25%, a quality fraction of (NH4)2SO4 18%, and an extraction temperature of 80°C. Under these conditions, the extraction rate of ALPs could reach 28.83%. FTIR, SEM and HPLC results showed that ALPs were typical acidic heteropolysaccharides and had uneven particle size distribution, an irregular shape, and a rough surface. The ALPs were chiefly composed of glucose, rhamnose, arabinose, and galactose with a molar ratio of 70.19:10.95:11.16:6.90. In addition, the ALPs had intense antioxidant activity in vitro with IC50 values in the ·OH radical (1.732 mg/ml), DPPH radical (0.29 mg/ml), and superoxide anion (0.15 mg/ml) scavenging abilities.DiscussionThe results showed that ATPS was an efficient method to extract polysaccharides and could be used for the extraction of other polysaccharides. These results indicated that ALPs had great prospects as a functional food and could be exploited in multiple fields.

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Section: Resultsmentioning

confidence: 99%

Extraction, structural characterization, and antioxidant activity of polysaccharides derived from Arctium lappa L.

Gao

Chen

et al. 2023

Front. Nutr.

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“…We identified 11 target miRNAs and 10 associated transcription factors to further understand the hub gene associations. Some miRNAs, such as miR-30b-5p ( Ren et al, 2021 ), miR-30a-5p ( Qian et al, 2022 ), and miR-155-5p ( Wang et al, 2022 ), can play a role in the pathological process of HF. The expression of BCL6 can be regulated by the transcription factors TEAD3, MYF6, ARNTL, ZNF581, MYOD1 and GLI2, and TEAD3 ( Han et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Uncovering the molecular mechanisms between heart failure and end-stage renal disease via a bioinformatics study

Bian

2023

Front. Genet.

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Background: Heart failure (HF) is not only a common complication in patients with end-stage renal disease (ESRD) but also a major cause of death. Although clinical studies have shown that there is a close relationship between them, the mechanism of its occurrence is unclear. The aim of this study is to explore the molecular mechanisms between HF and ESRD through comprehensive bioinformatics analysis, providing a new perspective on the crosstalk between these two diseases.Methods: The HF and ESRD datasets were downloaded from the Gene Expression Omnibus (GEO) database; we identified and analyzed common differentially expressed genes (DEGs). First, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set variation analyses (GSVA) were applied to explore the potential biological functions and construct protein−protein interaction (PPI) networks. Also, four algorithms, namely, random forest (RF), Boruta algorithm, logical regression of the selection operator (LASSO), and support vector machine-recursive feature elimination (SVM-RFE), were used to identify the candidate genes. Subsequently, the diagnostic efficacy of hub genes for HF and ESRD was evaluated using eXtreme Gradient Boosting (XGBoost) algorithm. CIBERSORT was used to analyze the infiltration of immune cells. Thereafter, we predicted target microRNAs (miRNAs) using databases (miRTarBase, TarBase, and ENOCRI), and transcription factors (TFs) were identified using the ChEA3 database. Cytoscape software was applied to construct mRNA−miRNA−TF regulatory networks. Finally, the Drug Signatures Database (DSigDB) was used to identify potential drug candidates.Results: A total of 68 common DEGs were identified. The enrichment analysis results suggest that immune response and inflammatory factors may be common features of the pathophysiology of HF and ESRD. A total of four hub genes (BCL6, CCL5, CNN1, and PCNT) were validated using RF, LASSO, Boruta, and SVM-RFE algorithms. Their AUC values were all greater than 0.8. Immune infiltration analysis showed that immune cells such as macrophages, neutrophils, and NK cells were altered in HF myocardial tissue, while neutrophils were significantly correlated with all four hub genes. Finally, 11 target miRNAs and 10 TFs were obtained, and miRNA−mRNA−TF regulatory network construction was performed. In addition, 10 gene-targeted drugs were discovered.Conclusion: Our study revealed important crosstalk between HF and ESRD. These common pathways and pivotal genes may provide new ideas for further clinical treatment and experimental studies.

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“…Previous results also suggest that PLGA nanoparticles represent a high potential for utilization in anticancer therapy due to their effectiveness and safety [ 27 ]. PLGA nanoparticles loaded with miR-30b-5p can improve cardiac function, attenuate myocardial injury, and regulate the expression of factors associated with cardiac hypertrophy and inflammation by targeting TGFBR2 [ 28 ]. PLGA nanoparticles are well known as promising delivery systems, especially in the area of nose-to-brain delivery by transcellular, intracellular and paracellular transport [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Lasting Exendin-4-Loaded PLGA Nanoparticles Ameliorate Cerebral Ischemia/Reperfusion Damage in Diabetic Rats

Chung

Cheng

et al. 2022

JPM

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Exendin-4 (Ex-4) is an incretin mimetic agent approved for diabetes treatment and neuronal protection. However, the required frequent injections restrict its clinical application. We prepared Ex-4-loaded poly(d,l-lactide-co-glycolide) nanoparticles (PEx-4) and investigated their effect on cerebral ischemia/reperfusion (IR) injury associated with micturition center damage-induced cystopathy in diabetic rats. Using ten minutes of bilateral carotid artery occlusion combined with hemorrhage-induced hypotension of the IR model in streptozotocin-induced type 1 diabetic (T1DM) Wistar rats, we compared the effects of Ex-4 and PEx-4 on prefrontal cortex edema, voiding function and oxidative stress including cerebral spinal fluid (CSF) reference H2O2 (RH2O2) and HOCl (RHOCl) levels, endoplasmic reticulum (ER) stress, apoptosis, autophagy and pyroptosis signaling in brain and bladder by Western blot and immunohistochemistry. Single injection of PEx-4 displayed higher CSF antioxidant activity and a long-lasting hypoglycemic effect compared to Ex-4 in rats. T1DM and IR primarily enhanced CSF RH2O2, and pIRE-1/caspase-12/pJNK/CHOP-mediated ER stress, caspase-3/PARP-mediated apoptosis, Beclin-1/LC3B-mediated autophagy and caspase-1/IL-1β-mediated pyroptosis signaling in the damaged brains. Our data further evidenced that PEx-4 were more efficient than Ex-4 in attenuating IR-evoked prefrontal cortex edema, the impairment in micturition center and the enhanced level of CSF RH2O2 and HOCl, ER stress, apoptosis, autophagy and pyroptosis parameters in the damaged brains, but had less of an effect on IR-induced voiding dysfunction in bladders of T1DM rats. In summary, PEx-4 with stronger antioxidant activity and long-lasting bioavailability may efficiently confer therapeutic efficacy to ameliorate IR-evoked brain damage through the inhibitory action on oxidative stress, ER stress, apoptosis, autophagy and pyroptosis signaling in diabetic rats.

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Mechanism of miR-30b-5p-Loaded PEG-PLGA Nanoparticles for Targeted Treatment of Heart Failure

Cited by 9 publications

References 39 publications

Extraction, structural characterization, and antioxidant activity of polysaccharides derived from Arctium lappa L.

Extraction, structural characterization, and antioxidant activity of polysaccharides derived from Arctium lappa L.

Uncovering the molecular mechanisms between heart failure and end-stage renal disease via a bioinformatics study

Long-Lasting Exendin-4-Loaded PLGA Nanoparticles Ameliorate Cerebral Ischemia/Reperfusion Damage in Diabetic Rats

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