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Epidemiological studies have implied that diabetes mellitus (DM) will become an epidemic accompany with metabolic and endocrine disorders worldwide. Most of DM patients are affected ...by type 2 diabetes mellitus (T2DM) with insulin resistance and insulin secretion defect. Generally, the strategies to treat T2DM are diet control, moderate exercise, hypoglycemic and lipid-lowing agents. Despite the therapeutic benefits for the treatment of T2DM, most of the drugs can produce some undesirable side effects. Considering the pathogenesis of T2DM, natural products (NPs) have become the important resources of bioactive agents for anti-T2DM drug discovery. Recently, more and more natural components have been elucidated to possess anti-T2DM properties, and many efforts have been carried out to elucidate the possible mechanisms. The aim of this paper was to overview the activities and underlying mechanisms of NPs against T2DM. Developments of anti-T2DM agents will be greatly promoted with the increasing comprehensions of NPs for their multiple regulating effects on various targets and signal pathways.
Clinical application of doxorubicin (DOX), an anthracycline antibiotic with potent anti- tumor effects, is limited because of its cardiotoxicity. However, its pathogenesis is still not entirely ...understood. The aim of this paper was to explore the mechanisms and new drug targets to treat DOX-induced cardiotoxicity. The in vitro model on H9C2 cells and the in vivo models on rats and mice were developed. The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px. Total of 18 differentially expressed microRNAs in rat heart tissue caused by DOX were screened out using microRNA microarray assay, especially showing that miR-140-5p was significantly increased by DOX which was selected as the target miRNA. Double-luciferase reporter assay showed that miR-140-5p directly targeted Nrf2 and Sirt2, as a result of affecting the expression levels of HO-1, NQO1, Gst, GCLM, Keap1 and FOXO3a, and thereby increasing DOX-caused myocardial oxidative damage. In addition, the levels of intracellular ROS were significantly increased or decreased in H9C2 cells treated with DOX after miR-140-5p mimic or miR-140-5p inhibitor transfection, respectively, as well as the changed expression levels of Nrf2 and Sirt2. Furthermore, DOX- induced myocardial oxidative damage was worsened in mice treated with miR-140-5p agomir, and however the injury was alleviated in the mice administrated with miR-140-5p antagomir. Therefore, miR-140-5p plays an important role in DOX-induced cardiotoxicity by promoting myocardial oxidative stress via targeting Nrf2 and Sirt2. Our data provide novel insights for investigating DOX-induced heart injury. In addition, miR-140-5p/ Nrf2 and miR-140-5p/Sirt2 may be the new targets to treat DOX-induced cardiotoxicity.
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•DOX significantly increased the levels of miR-140-5p in vitro and in vivo.•MiR-140-5p aggravated DOX-induced cardiotoxicity.•MiR-140-5p promoted myocardial oxidative stress.•MiR-140-5p directly targeted Nrf2 and Sirt2.•MiR-140-5p may be the new target of DOX-induced cardiotoxicity.
The exposure risk of metal-based nanoparticles (NPs) to marine organisms and related food safety have attracted increasing attention, but the actual concentrations of these NPs in seawater and marine ...organisms are unknown. In this work, single particle inductively coupled plasma-mass spectrometry (spICP-MS) was used to quantify the concentrations and size distributions of NPs in different marine mollusks (oysters, mussels, scallops, clams, and ark shells) from an offshore aquaculture farm. Results showed that Ti, Cu, Zn, and Ag bearing NPs were detected in all the five mollusks with the mean sizes at 65.4–70.9, 72.2–89.6, 97.8–108.3, and 42.9–51.0 nm, respectively. The particle concentrations of Ti, Cu, Zn, and Ag bearing NPs in all mollusks (0.88–3.26 × 107 particles/g fresh weight) were much higher than that in the seawater (0.46–0.79 × 107 particles/mL), suggesting bio-accumulation of NPs. For all the five mollusks, Ag bearing NPs had the highest number-based bioconcentration factors (NBCFs) in all the tested NPs due to the smallest mean size of Ag bearing NPs in seawater (30.5 nm). In addition, the clams exhibited the lowest NBCFs of the four NPs than other mollusks. All four NPs were mainly accumulated in the gill and digestive gland, and could transfer to adductor muscle of all mollusks. Although all the four metals (Ti, Cu, Zn, Ag) in mollusks were safe for human consumption by the estimated daily intake (EDI) analysis, the risk of NPs remaining in the mollusks should be further considered when evaluating the toxicity of metals for human health. The findings could improve our understanding on the distribution and health risk of NPs in marine mollusks under offshore aquaculture.
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•The particle number of four NPs in mollusks followed an order of Cu > Ti ≈ Ag > Zn.•Ag bearing NPs had higher accumulation in mollusks than Ti, Cu, and Zn bearing NPs.•Four NPs were mainly accumulated in gill and digestive gland of mollusks.•NPs distributed in adductor muscle were smaller than those in other tissues.
Ti, Cu, Zn, and Ag bearing nanoparticles were detected in all the five marine mollusks, and had bio-accumulation in mollusks.
The electrocatalysis toward small molecules, especially small organic compounds, is of importance in a variety of areas. Nickel based materials such as nickel, its oxides, hydroxides as well as ...oxyhydroxides exhibit excellent electrocatalysis performances toward many small molecules, which are widely used for fuel cells, energy storage, organic synthesis, wastewater treatment, and electrochemical sensors for pharmaceutical, medical, food or environmental analysis. Their electrocatalytic mechanisms are proposed from three aspects such as Ni(OH)2/NiOOH mediated electrolysis, direct electrocatalysis of Ni(OH)2 or NiOOH. Under exposure to air or aqueous solution, two distinct layers form on the Ni surface with a Ni hydroxide layer at the air-oxide interface and an oxide layer between the metal substrate and the outer hydroxide layer. The transformation from nickel or its oxides to hydroxides or oxyhydroxides could be further speeded up in the strong alkaline solution under the cyclic scanning at relatively high positive potential. The redox transition between Ni(OH)2 and NiOOH is also contributed to the electrocatalytic oxidation of Ni and its oxides toward small molecules in alkaline media. In addition, nickel based materials or nanomaterials, their preparations and applications are also overviewed here.
Clinical application of doxorubicin (DOX) is limited because of its cardiotoxicity. Thus, exploration of effective lead compounds against DOX-induced cardiotoxicity is necessary. The aim of the ...present study was to investigate the effects and possible mechanisms of dioscin against DOX-induced cardiotoxicity. The in vitro model of DOX- treated H9C2 cells and the in vivo models of DOX-treated rats and mice were used in this study. The results showed that discoin markedly increased H9C2 cell viability, decreased the levels of CK, LDH, and improved histopathological and electrocardio- gram changes in rats and mice to protect DOX-induced cardiotoxicity. Furthermore, dioscin significantly inhibited myocardial oxidative insult through adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px in vitro and in vivo. Our data also indicated that dioscin activated Nrf2 and Sirt2 signaling pathways, and thereby affected the expression levels of HO-1, NQO1, Gst, GCLM, Keap1 and FOXO3a through decreasing miR-140-5p expression level. In addition, the level of intracellular ROS was significantly increased in H9C2 cells treated by DOX after miR-140-5p mimic transfection, as well as the down-regulated expression levels of Nrf2 and Sirt2, which were markedly reversed by dioscin. In conclusion, our data suggested that dioscin alleviated DOX-induced cardiotoxicity through modulating miR-140-5p-mediated myocardial oxidative stress. This natural product should be developed as a new candidate to alleviate cardiotoxicity caused by DOX in the future.
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•Dioscin significantly alleviated DOX-induced cardiotoxicity.•Dioscin markedly inhibited myocardial oxidative stress.•Dioscin significantly decreased the levels of miR-140-5p in vitro and in vivo.•Dioscin activated Nrf2 and Sirt2 signal pathways in vitro and in vivo.•Dioscin may be a new potential candidate for DOX-induced cardiotoxicity.
Trapping graphene at the interface of a poly(ε-caprolactone) (PCL)/poly(lactic acid) (PLA) blend is achieved through the adsorption-desorption of polymer chains on the graphene surface. The resulting ...composite exhibits remarkably high thermal conductivity due to the graphene sheets being controlled at the interface of the polymer blend. At 0.53 vol%, when a good co-continuous structure is formed, the thermal conductivity of the graphene composite is nearly 4 times higher than that of the pure PCL/PLA blend with co-continuous structure. Moreover, the blend achieves an extremely low thermal percolation threshold (0.11 vol%), the lowest to date, because most of the graphene sheets are selectively located at the interface of the blend with co-continuous structure.
The pile with ram-compacted bearing sphere (PRBS)is a kind of special-shaped pile, the calculation formula of single pile bearing capacity stipulated in Chinese Standards JGJ/T 135-2018 is relatively ...simple, and the factors considered are not comprehensive enough. This article uses the finite element simulation software ABAQUS to simulate and calculate the compressive bearing characteristics of PRBS, and studies the changes in the vertical bearing characteristics of PRBS under different factors and working conditions (different pile lengths, pile diameters, and the diameters of ram-compacted bearing sphere (RBS)). The calculation results indicate that the PRBS still has a large axial force near the enlarged end of the pile bottom, and the RBS bears a large load. The vertical bearing capacity of the PRBS is mainly provided by the RBS, but the pile side friction still has a certain degree of influence on its bearing capacity. The maximum ratio of pile side frictional resistance to applied load can reach 18.41%. Compared with the ordinary pile, the bearing capacity of the PRBS is significantly improved. The ultimate bearing capacity of the PRBS with the RBS diameter of 1m is more than 5 times that of the ordinary pile under the same condition. Pile diameter has little influence on the bearing capacity of PRBS, while the change of RBS diameter has great influence on the bearing capacity of single pile. However, when the RBS diameter is too large, it is easy to cause the uplift of surrounding soil in the construction process and affect surrounding piles. Therefore, it is suggested that the optimal RBS diameter should be 800mm~1200mm. This study provides reference suggestions for the study of piles with ram-compacted bearing sphere.
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•Dioscin showed protective effect against fructose-induced kidney injury in rats.•Dioscin improved oxidative damage and renal fibrosis caused by fructose in rats.•Dioscin improved ...lipid metabolism and inflammation caused by fructose in rats.•Dioscin up-regulated the expression level of Sirt3.
In the present work, the effects and possible mechanisms of dioscin, one natural product from the famous vegetable Dioscoreae rhizoma (Shanyao in Chinese), against high fructose-induced renal injury in rats were tested. The results showed that dioscin significantly restored fructose-induced renal injury by decreasing the levels of Cr, BUN, and rehabilitating histopathological changes. In addition, dioscin markedly adjusted the levels of MDA, SOD and GSH-Px, reduced ROS level in renal tissue, and decreased the levels of TG, FFA, α-SMA and COL1A. Mechanistic study showed that dioscin significantly up-regulated the expression levels of Sirt3, SOD2, and then suppressed inflammation by decreasing the expression levels of NF-kB, HMGB1, c-Jun, c-Fos, COX2, TNF-α, IL-1β and IL-6. Furthermore, dioscin-caused high levels of Sirt3 and SOD2 attenuated oxidative stress by regulating the expression levels of Nrf2, GST, Keap1, regulated lipid metabolism by controlling the expression levels of SREBP-1c, SCD-1, FASn, ACC, CPT1, and adjusted TGF-β1/Smad signal to inhibit renal fibrosis. In summary, dioscin showed protective effects against fructose-induced renal damage via adjusting Sirt3-mediated oxidative stress, renal fibrosis, lipid metabolism and inflammation, which should be considered as one candidate to treat renal injury in the future. We also suggest that the patients with renal injury can take more Shanyao for the therapy and treatment.
A novel electrochemical sensor using the molecularly imprinted (MIP) oxygen-containing polypyrrole (PPy) decorated carbon nanotubes (CNTs) composite was proposed for in vivo detection of dopamine ...(DA). The prepared sensor exhibits a remarkable sensitivity of (16.18μA/μM) with a linear range of 5.0×10−11–5.0×10−6M and limit of detection as low as 1.0×10−11M in the detection of DA, which might be due to the plenty cavities for binding DA through π–π stacking between aromatic rings and hydrogen bonds between amino groups of DA and oxygen-containing groups of the novel PPy.
•Novel strategy to improve the sensitivity of CNTs polymer composite sensors was proposed.•PPy/CNTs-MIPs with plenty oxygen-containing groups was facilely synthesized.•Oxygen-containing groups of PPy could establish strong hydrogen bonds with amino groups of DA.•PPy/CNTs-MIPs sensor offered a nanomole level detection for DA in biological systems.
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As one classic anticancer drug, clinical application of Doxorubicin (Dox) is limited due to its side effects. In our previous work, we have investigated the drug targets to treat ...Dox-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. In this paper, the mechanisms and new drug-target associated with Dox-induced hepatotoxicity were explored. The results showed that Dox markedly inhibited cell viability and cellular respiration, induced cell morphologic change and increased ROS level. Moreover, Dox increased ALT and AST levels, caused pathological damage, increased MDA level and decreased SOD level in mice. Mechanism investigation showed that Dox markedly up-regulated the expression level of miR-128-3p, down-regulated Sirt1 expression level and affected the protein levels of Nrf2, Keap1, Sirt3, NQO1 and HO-1 to cause oxidative stress in liver. Furthermore, double-luciferase reporter assay, and co-transfection test showed that miR-128-3p directly targeted Sirt1. In addition, miR-128-3p mimics in AML-12 cells enhanced Dox-induced oxidative damage via inhibiting cellular respiration, increasing ROS level and mitochondrial superoxide formation. The protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1 in miR-128-3p mimic + Dox group were decreased compared with Dox group. Transfection of miR-128-3p inhibitor weakened Dox-induced oxidative damage via increasing cellular respiration, suppressing cellular ROS level and mitochondrial superoxide formation. The protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1 in miR-128-3p inhibitor + Dox group were increased compared with Dox group. In mice, Dox-induced liver damage was deteriorated by miR-128-3p agomir via increasing the levels of ALT, AST, MDA, and down-regulating the protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1. While, miR-128-3p antagomir alleviated liver injury via decreasing the levels of ALT, AST, MDA, and up-regulating the protein levels of Sirt1, Nrf2, Sirt3, NQO1 and HO-1. Our data showed that miRNA-128-3p aggravated Dox-induced liver injury by promoting oxidative stress via targeting Sirt1, which should be considered as one new drug target to treat Dox-induced liver injury.
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