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The usage of doxorubicin is hampered by its life-threatening cardiotoxicity in clinical practice. Dexrazoxane is the only cardioprotective medicine approved by the FDA for preventing doxorubicin-induced cardiac toxicity. Nevertheless, the mechanism of dexrazoxane is incompletely understood. The aim of our study is to investigate the possible molecular mechanism of dexrazoxane against doxorubicin-induced cardiotoxicity. We established a doxorubicin-induced mouse and cardiomyocyte injury model. Male C57BL/6J mice were randomly distributed into a control group (Con), a doxorubicin treatment group (DOX), a doxorubicin plus dexrazoxane treatment group (DOX+DEX), and a dexrazoxane treatment group (DEX). Echocardiography and histology analyses were performed to evaluate heart function and structure. DNA laddering, qRT-PCR, and Western blot were performed on DOX-treated cardiomyocytes with/without DEX treatment in vitro. Cardiomyocytes were then transfected with miR-17-5p mimics or inhibitors in order to analyze its downstream target. Our results demonstrated that dexrazoxane has a potent effect on preventing cardiac injury induced by doxorubicin in vivo and in vitro by reducing cardiomyocyte apoptosis. MicroRNA plays an important role in cardiovascular diseases. Our data revealed that dexrazoxane could upregulate the expression of miR-17-5p, which plays a cytoprotective role in response to hypoxia by regulating cell apoptosis. Furthermore, the miRNA and protein analysis revealed that miR-17-5p significantly attenuated phosphatase and tensin homolog (PTEN) expression in cardiomyocytes exposed to doxorubicin. Taken together, dexrazoxane might exert a cardioprotective effect against doxorubicin-induced cardiomyocyte apoptosis by regulating the expression of miR-17-5p/PTEN cascade.

Chronic hypertension, valvular heart disease, and heart infarction cause cardiac remodeling and potentially lead to a series of pathological and structural changes in the left ventricular myocardium and a progressive decrease in heart function. Angiotensin II (AngII) plays a key role in the onset and development of cardiac remodeling. Many microRNAs (miRNAs), including miR-154-5p, may be involved in the development of cardiac remolding, but the underlying molecular mechanisms remain unclear. We aimed to characterize the function of miR-154-5p and reveal its mechanisms in cardiac remodeling induced by AngII. First, angiotensin II led to concurrent increases in miR-154-5p expression and cardiac remodeling in adult C57BL/6J mice. Second, overexpression of miR-154-5p to a level similar to that induced by AngII was sufficient to trigger cardiomyocyte hypertrophy and apoptosis, which is associated with profound activation of oxidative stress and inflammation. Treatment with a miR-154-5p inhibitor noticeably reversed these changes. Third, miR-154-5p directly inhibited arylsulfatase B (Arsb) expression by interacting with its 3′-UTR and promoted cardiomyocyte hypertrophy and apoptosis. Lastly, the angiotensin type 1 receptor blocker telmisartan attenuated AngII-induced cardiac hypertrophy, apoptosis, and fibrosis by blocking the increase in miR-154-5p expression. Moreover, upon miR-154-5p overexpression in isolated cardiomyocytes, the protective effect of telmisartan was partially abolished. Based on these results, increased cardiac miR-154-5p expression is both necessary and sufficient for AngII-induced cardiomyocyte hypertrophy and apoptosis, suggesting that the upregulation of miR-154-5p may be a crucial pathological factor and a potential therapeutic target for cardiac remodeling.

A method of ultrasonic-assisted extraction followed by high-speed countercurrent chromatography was established for the extraction and isolation of three flavonoid glycosides, i.e. rutin, narcissin, and nicotiflorin from Flos Sophorae Immaturus. The effects of ultrasonic-assisted extraction factors for the main flavonoid compound (rutin) from Flos Sophorae Immaturus were optimized using Box-Behnken design combined with response surface methodology. The optimum conditions were determined as ultrasonic power 83% (600 W), solvent-to-material ratio 56:1, methanol concentration 82% v/v, and extraction time 60 min. Three bioactive flavonol glucosides, rutin, narcissin, and nicotiflorin were isolated from Flos Sophorae Immaturus using high-speed countercurrent chromatography. The separation was performed with a two-phase solvent system containing ethyl acetate/n-butanol/methanol/water (4:0.9:0.2:5, v/v). Amounts of 87 mg of rutin, 10.8 mg of narcissin, and 1.8 mg of nicotiflorin were isolated from 302 mg of crude extract of Flos Sophorae Immaturus in a one-step separation within 160 min with purities of 99.3, 98.0, and 95.1%, respectively, as determined by HPLC with diode array detection. Their structures were characterized by UV, MS, and NMR spectroscopy. It was demonstrated that the established method was simple, fast, and convenient, which was feasible to extract and isolate active flavonoid glycosides from Flos Sophorae Immaturus.

In the current study, we investigate changes in CD4+CD25+ cells in chickens during infectious bursal disease virus (IBDV) infection. The percentage of CD4+CD25+ cells in lymph organs, e.g., the thymus, spleen, bursa of Fabricius and peripheral blood, during the first 1–5 days post infection (dpi) was assessed by flow cytometry. The data revealed a remarkable decrease in the percentage of CD4+CD25+ cells in the thymus from 1 to 5 dpi and in the spleen during early infection. An increase of the percentage of CD4+CD25+ cells among peripheral blood lymphocytes was observed during the first two days of IBDV infection. Additionally, CD4+CD25+ cells infiltrated the bursa along with CD4+ cells after IBDV infection. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the mRNA levels of immune-related cytokines in IBDV-infected thymus and bursa of Fabricius tissues. The data revealed that IBDV caused a significant increase in interleukin (IL)-10 mRNA levels, with the Harbin-1 strain (vvIBDV) inducing higher IL-10 expression than the Ts strain. Taken together, our data suggest that chicken CD4+CD25+ cells may participate in IBDV pathogenicity by migrating from their sites of origin and storage, the thymus and spleen, to the virally targeted bursa of Fabricius during IBDV infection.

Volatile components from Exocarpium Citri Grandis (ECG) were, respectively, extracted by three methods, that is, steam distillation (SD), headspace solid-phase microextraction (HS-SPME), and solvent extraction (SE). A total of 81 compounds were identified by gas chromatography-mass spectrometry including 77 (SD), 56 (HS-SPME), and 48 (SE) compounds, respectively. Despite of the extraction method, terpenes (39.98~57.81%) were the main volatile components of ECG, mainly germacrene-D, limonene, 2,6,8,10,14-hexadecapentaene, 2,6,11,15-tetramethyl-, (E,E,E)-, and trans-caryophyllene. Comparison was made among the three methods in terms of extraction profile and property. SD relatively gave an entire profile of volatile in ECG by long-time extraction; SE enabled the analysis of low volatility and high molecular weight compounds but lost some volatiles components; HS-SPME generated satisfactory extraction efficiency and gave similar results to those of SD at analytical level when consuming less sample amount, shorter extraction time, and simpler procedure. Although SD and SE were treated as traditionally preparative extractive techniques for volatiles in both small batches and large scale, HS-SPME coupled with GC/MS could be useful and appropriative for the rapid extraction and qualitative analysis of volatile components from medicinal plants at analytical level.

Since the 1980-1990s, international research efforts have augmented our knowledge of the physical and chemical properties of the Arctic Ocean water masses, and recent studies have documented changes. Understanding the processes responsible for these changes is necessary to be able to forecast the local and global consequences of these property evolutions on climate. The present work investigates the distributions of geochemical tracers of particle fluxes and circulation in the Amerasian Basin and their temporal evolution over the last three decades (from stations visited between 1983 and 2015). Profiles of 230-thorium ( 230 Th) and 231-protactinium ( 231 Pa) concentrations and neodymium isotopes (expressed as ε Nd ) measured in the Amerasian Basin prior to 2000 are compared to a new, post-2000s data set. The comparison shows a large scale decrease in dissolved 230 Th and 231 Pa concentrations, suggesting intensification of scavenging by particle flux, especially in coastal areas. Higher productivity and sediment resuspension from the shelves appear responsible for the concentration decrease along the margins. In the basin interior, increased lateral exchanges with the boundary circulation also contribute to the decrease in concentration. This study illustrates how dissolved 230 Th and 231 Pa, with ε Nd support, can provide unique insights not only into changes in particle flux but also into the evolution of ocean circulation and mixing. Plain Language SummaryThe Arctic Ocean is one of the oceanic regions most affected by climate change. The increasing summer retreat of sea ice allows greater atmosphere-ocean exchanges and light penetration, while land-ocean exchanges are expected to increase, due to enhanced continental erosion (notably through permafrost thawing and increased river flow). These changes are driven by climate and in turn impact the climate. This study aims at assessing possible shifts in oceanic circulation and particle fluxes resulting from these climate-driven changes in the Amerasian Basin of the Arctic Ocean, during the last few decades. To achieve this goal, we measured geochemical tracers of circulation and particle fluxes in seawater samples collected in this area between 2005 and 2015, which we compared to published data from samples collected between 1983 and 2000. The primary geochemical tracers studied here are 230 Th and 231 Pa. These radioisotopes are uniformly produced in seawater, from uranium decay, and are strongly reactive with particles. Therefore, their oceanic distribution depends on particle fluxes and circulation. The evolution of their distribution in the Amerasian Basin over space and time documents enhancement of particle flux and lateral mixing in the Amerasian basin of the Arctic Ocean over the last three decades. Key Points: • Concentration decreases of 230 Th d and 231 Pa d suggest an enhancement of particulate scavenging since the 2000s in the Amerasian Basin • Particulate scavenging results from higher productivity and sediment resuspension from the shelves • Post-2...

Lipid digestion characteristics in human, bovine, and caprine milk were investigated using an infant in vitro digestion model. Our results suggested that particle size in bovine and caprine milk increased initially and then decreased over time, whereas the particle size in human milk continuously decreased. The lipolysis degree of human milk (86.8%) was higher than that in bovine (80.2%) and caprine (82.7%) milk (P < 0.05). Compared to human milk, bovine and caprine milk released higher unsaturated fatty acids and lower SFAs. In addition, 12 and 84 glyceride species were significantly different between bovine and human milk, during gastrointestinal digestion (P < 0.05). Another 13 and 92 glyceride species were found to be significantly different between caprine and human milk. A total of 30 and 31 lipids were screened as biomarkers to further clarify the differences related to lipid digestion properties of human, bovine, and caprine milk.