N-3 polyunsaturated fatty acids attenuate amyloid-beta-induced toxicity in AD transgenic Caenorhabditis elegans via promotion of proteasomal activity and activation of PPAR-gamma.

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of ß-amyloid (Aß), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aß-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aß-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aß in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aß by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aß-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aß-induced toxicity.

Improved solar-driven water purification using an eco-friendly and cost-effective aerogel-based interfacial evaporator with exceptional photocatalytic capabilities.

As a promising solution to address the global challenge of freshwater scarcity, solar-powered interfacial steam generation has undergone notable advancements. This study introduces a novel solar-driven interfacial evaporation membrane (ZnIn2S4@SiO2/ACSA, ZSAS) comprising a ZnIn2S4@SiO2 composite and a black sodium alginate aerogel infused with activated carbon. The ZSAS membrane demonstrates exceptional light absorption and thermal insulation, leading to elevated surface temperatures and reduced heat dissipation into the bulk water. Furthermore, the incorporation of AC reinforces the mechanical properties of the ZSAS membrane and enhances the water purification performance. These collective features result in an impressive evaporation rate of 1.485 kg m-2 h-1 and a high photothermal conversion efficiency of 91.2% under 1 sun irradiation for the optimal ZSAS membrane. Moreover, the optimal ZSAS membrane can effectively remove salts, heavy metal ions, and organic pollutants, benefitting from its superior evaporation separation effect and the photocatalytic properties of the ZnIn2S4@SiO2 composite.

[Retracted] MicroRNA­9 limits hepatic fibrosis by suppressing the activation and proliferation of hepatic stellate cells by directly targeting MRP1/ABCC1.

Following the publication of this article, a concerned reader drew to our attention that in Fig. 5C on p. 1704, showing histological images of mouse livers stained with H&E, unexpected areas of similarity were identified in terms of the staining patterns revealed within the data panels themselves. After having conducted an internal investigation, the Editor of Oncology Reports has reached the conclusion that the overlapping portions of data shown in this figure were unlikely to have arisen by coincidence. Therefore, on the grounds of a lack of confidence in the integrity of these data, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused, and thanks the interested reader for drawing this matter to our attention. [Oncology Reports 37: 1698­1706, 2017; DOI: 10.3892/or.2017.5382].

MiR-139-5p inhibits proliferation and promoted apoptosis of human airway smooth muscle cells by downregulating the Brg1 gene.

MicroRNAs have emerged as critical regulators in the pathogenesis of asthma. However, the role of microRNAs in asthma needs to be further elucidated. In this study, we found that miR-139-5p was greatly decreased in airway smooth muscle (ASM) cells from asthmatic humans as well as ASM cells stimulated with cytokines. Overexpression of miR-139-5p markedly suppressed ASM cell proliferation and promoted cell apoptosis, whereas knockdown of miR-139-5p had the opposite effect. Further study verified that Brg1, a chromatin remodeling factor, was upregulated in ASM cells treated with cytokines and acted as a direct target of miR-139-5p. Ectopic expression of Brg1 partially reversed the effect of miR-139-5p on cell proliferation and apoptosis. Moreover, overexpression of Brg1 restored miR-139-5p-induced downregulation of Akt and p70S6K phosphorylation. Together, these data indicate that miR-139-5p may function as a key regulator of ASM cell proliferation and apoptosis, potentially by targeting the Brg1 gene, and thus suggesting a potential role of miR-139-5p in the pathogenesis of asthma.

MicroRNA-9 limits hepatic fibrosis by suppressing the activation and proliferation of hepatic stellate cells by directly targeting MRP1/ABCC1.

Liver fibrosis is a chronic liver disease characterized by the proliferation and activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM). Research suggests that microRNAs (miRNAs) are a new type of regulator of liver fibrosis. In the present study, we investigated the role of microRNA-9 (miR-9) in the process of liver fibrosis, as well as the underlying mechanism of action. Downregulated levels of miR-9 were found in fibrotic liver tissues and activated HSCs as detected by qRT-PCR; whereas, expression of multidrug resistance­associated protein 1 (MRP1/ABCC1) was upregulated in the fibrotic liver tissues and activated HSCs. CCK-8 and BrdU assays revealed that miR-9 reduced the proliferative ability of the HSCs. In addition, expression levels of ECM-related genes (α-SMA, Col-1 and Timp-1), which are markers of HSC activation, were downregulated by miR-9. Conversely, an miR-9 inhibitor promoted cell proliferation and HSC activation. In addition, a luciferase reporter assay indicated that miR-9 targets the 3'-untranslated region (3'-UTR) of MRP1 and causes a significant decrease in MRP1. miR-9 inhibited the activation of the Hedgehog (Hh) pathway and the expression of MRP1, while this suppression was rescued by the overexpression of MRP1. Finally, a CCl4-induced mouse model of liver fibrosis was used to investigate the effects of miR-9 on liver fibrosis in vivo. The results showed that miR-9 abrogated hepatic fibrosis by suppressing the expression of MRP1 in CCl4-induced liver fibrotic mice. In conclusion, the present study demonstrated that miR-9 suppresses the proliferation and activation of HSCs through the Hh pathway by targeting MRP1, which suggests that miR-9 has therapeutic potential for liver fibrosis.

Novel transferrin modified and doxorubicin loaded Pluronic 85/lipid-polymeric nanoparticles for the treatment of leukemia: In vitro and in vivo therapeutic effect evaluation.

PURPOSE: Childhood leukemia is a common malignant disease in children. Doxorubicin (DOX) was widely used for the treatment of leukemia. However, severe toxic side effects and drug resistance are the major limitations of DOX. Nanocarriers offer the opportunity to overcome these drawbacks, there are many attempts to enhance the activity of DOX against drug resistance. This study aimed to develop a novel transferrin (Tf) modified and doxorubicin (DOX) loaded Pluronic 85/lipid-polymeric nanoparticles for the treatment of leukemia. METHODS: In this study, a novel targeted ligand: transferrin-polyethylene glycol-oleic acid (Tf-PEG-OA) was synthesized. Tf modified and DOX loaded Pluronic 85/lipid-polymeric nanoparticles (Tf-DOX P85/LPNs) were prepared via the self-assembly of PLGA, P85, stearic acid and Tf-PEG-OA using the nanoprecipitation method. The physicochemical properties of LPNs were characterized. In vitro and in vivo anti-tumor efficacy of LPNs was evaluated in human promyelocytic leukemia cell line (HL-60 cells) and DOX resistance HL-60 cell line (HL-60/DOX cells) including the relevant animal models. RESULTS: Tf-DOX P85/LPNs displayed strong anti-tumor ability on both HL-60 cells and HL-60/DOX cells than other formulations used as contrast. Also, in HL-60/DOX bearing animal models, Tf-DOX P85/LPNs exhibited the highest efficiency as well as the lowest systemic toxicity. CONCLUSION: The results indicated that Tf P85/LPNs is a promising platform to enhance efficacy, reduce toxicity and overcome drug resistance of DOX for the treatment of leukemia.

A ROS-mediated lysosomal-mitochondrial pathway is induced by a novel Amonafide analogue, 7c, in human Hela cervix carcinoma cells.

In this study, a novel naphthalimide derivative 7c was designed which is topo II inhibiting though owning weak DNA binders. It was shown that 7c could induce cancer cells apoptosis and have less cytotoxicity in normal human cell. Further investigations on Hela cells revealed that 7c could also induce ROS generation, lysosome rupture as well as cathepsin B release. Subsequent mitochondrial damages including mitochondrial membrane permeabilization and the release of cytochrome c were also found in 7c when treating with Hela cells. According to our data, 7c may act as a lead compound for potential anticancer drugs. The idea of naphthalimides modification may also provide a novel strategy for naphthalimides design.

7-b, a novel amonafide analogue, cause growth inhibition and apoptosis in Raji cells via a ROS-mediated mitochondrial pathway.

Previous studies have shown that 7-b (6-(dodecylamino)-2-(3-(4-methylpiperazin-1-yl)propyl)-1H-benzo-[de]isoquinoline-1,3(2H)-dione), a novel amonafide-based DNA intercalator, was generated as a new anticancer candidate. However, the effects induced by 7-b and the molecular mechanisms involved remain poorly understood in Burkitt's lymphoma. To shed light on these issues, we have investigated the effects of 7-b on proliferation, cell cycle progression, apoptosis activity and oxidative stress levels of lymphoma Raji cells in vitro. Our results showed that 7-b inhibited the proliferation of Raji cells and induced G1 cell cycle arrest in a dose-dependent manner. Moreover, 7-b treatment triggered programmed cell death, production of reactive oxygen species (ROS) and alteration of the mitochondrial membrane potential (Δψm). Altogether our results showed that 7-b mediated its growth inhibitory effects on Raji cells via the activation of a ROS-mediated mitochondrial pathway and cell cycle checkpoint signaling pathway which subsequently targeted p21.

A new class of naphthalimide-based antitumor agents that inhibit topoisomerase II and induce lysosomal membrane permeabilization and apoptosis.

Based on the advantages of multitarget drugs for cancer treatment, a new class of naphthalimides was designed, synthesized, and proved to inhibit topoisomerase II (topo II), induced lysosomal membrane permeabilization (LMP), and ultimately caused apoptosis and cell death. The majority of compounds 7a-d and 8a-d potently inhibited the growth of the five tested cancer cell lines with IC(50) values ranging from 2 to 10 microM and are more active than amonafide, a naphthalimide that was in phase III clinical trials. These compounds were tested for their interactions with DNA and their cell-free topo II inhibition activities, which demonstrated these compounds were weak DNA binders but modest topo II inhibitors. Furthermore, compounds 7b-d were found to notably induce LMP and exhibited better antiproliferative activity compared with their single-target analogues. All of the newly synthesized compounds were demonstrated to efficiently induce apoptosis via a mitochondrial pathway. Accordingly, a new paradigm was suggested for the design of novel multitarget anticancer drugs.