RESUMEN

Acute liver injury (ALI) has an elevated fatality rate due to untimely and ineffective treatment. Although, schisandrin B (SchB) has been extensively used to treat diverse liver diseases, its therapeutic efficacy on ALI was limited due to its high hydrophobicity. Palmitic acid-modified serum albumin (PSA) is not only an effective carrier for hydrophobic drugs, but also has a superb targeting effect via scavenger receptor-A (SR-A) on the M1 macrophages, which are potential therapeutic targets for ALI. Compared with the common macrophage-targeted delivery systems, PSA enables site-specific drug delivery to reduce off-target toxicity. Herein, we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI. In vitro, compared with human serum albumin encapsulated SchB nanoparticles (SchB-HSA NPs), the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide (LPS) stimulated Raw264.7 (LAR) cells, and LAR cells took up PSA NPs 8.79 times more than HSA NPs. As expected, the PSA NPs also accumulated more in the liver. Moreover, SchB-PSA NPs dramatically reduced the activation of NF-κB signaling, and significantly relieved inflammatory response and hepatic necrosis. Notably, the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%. Hence, SchB-PSA NPs are promising to treat ALI.

RESUMEN

With the advanced discoveries in the field of pathogenesis, a series of cerebral diseases, such as cerebral ischaemia, Alzheimer's disease, and depression, have been found to have multiple signalling targets in the microenvironment. Only a few existing agents have been shown to have curative effects due to this specific circumstance. In recent decades, active ingredients isolated from natural plants have been shown to be crucial for original drug development. Geniposide, mainly extracted from Gardenia jasminoides Ellis, is representative of these natural products. Geniposide demonstrates various biological activities in the treatment of cerebral, cardiovascular, hepatic, tumorous, and other diseases. The multiple protective effects of geniposide on the brain have especially drawn increasing attention. Thus, this article specifically reviews the characteristics of current models of cerebral ischaemia and illustrates the possible effects of geniposide and its pathogenetic mechanisms on these models. Geniposide has been shown to significantly reduce the area of cerebral infarction and alleviate neuronal damage and necrosis mainly by inhibiting inflammatory signals, including NLRP3, TNF-α, IL-6, and IL-1ß. Neuronal protection was also involved in activating the PI3K/Akt and Wnt/catenin pathways. Geniposide was able to increase autophagy and inhibit apoptosis by regulating the function of mTOR in treating Alzheimer's disease. Geniposide has also been shown to act as a glucagon-like peptide-1 receptor (GLP-1R) agonist to reduce amyloid plaques and inhibit oxidative stress to alleviate memory impairment as well as synaptic loss. Moreover, geniposide has been shown to exert antidepressant effects primarily by regulating the hypothalamic-pituitary-adrenal (HPA) axis. Detailed explorations have shown that the biological activities of inhibiting inflammatory cytokine secretion, alleviating oxidative stress, and suppressing mitochondrial damage are also involved in the mechanism of action of geniposide. Therefore, geniposide is a promising agent awaiting further exploration for the treatment of cerebral diseases via various phenotypes or signalling pathways.

RESUMEN

Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)­218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR­218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR­218 in XWLC­05 cells were markedly lower compared with those in immortalized lung epithelial BEAS­2B cells. The present study also demonstrated that overexpression of miR­218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC­05 and NSCLC cell line NCI­H157. Additionally, the results revealed that overexpression of miR­218 could induce XWLC­05 and NCI­H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR­218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B­cell lymphoma 2 (BCL­2) and BMI1 proto­oncogene, polycomb ring finger (BMI­1) at the mRNA and protein level in XWLC­05 and NCI­H157 cell lines. However, we did not observe any remarkable difference in the roles of miR­218 and miR­218­mediated regulation of BCL­2, BMI­1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR­218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL­2 and BMI­1 in Xuanwei lung cancer. The results demonstrated that miR­218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR­218 may be a novel approach for the treatment of Xuanwei lung cancer.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación hacia Abajo , Neoplasias Pulmonares/genética , MicroARNs/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Supervivencia Celular , China , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo

RESUMEN

Mesoporous molecularly imprinted polymers (MIPs) containing mangnanese-doped ZnS quantum dots (Mn-ZnS QDs) were prepared for specific recognition and detection of 4-nitrophenol (4-NP). The Mn-ZnS QDs display orange room-temperature phosphorescence with excitation/emission peaks at 295/590 nm and a decay time of 2.0 ms. In the presence of 4-NP, the orange phosphorescence is strongly reduced. Phosphorescence drops linearly in the 0.1-100 µM 4-NP concentration range, and the detection limit is 60 nM. The detection limit is far lower than the maximally allowed 4-NP concentrations in surface water and drinking water as specified by the U.S. Environmental Protection Agency. The intraday (n = 5) and interday (n = 6) spiked recovery rates were 96.0-104.5% and 97.9-107.9%, respectively, with relative standard deviations of 0.7-4.8% and 1.8-7.5% respectively. These MIPs integrated the characteristic features of phosphorimetry and molecular imprinting. Potential interference by competitive substances, background fluorescence or scattered light are widely reduced. Graphical abstract Schematic presentation of the synthesis of phosphorescent molecularly-imprinted polymers. A novel probe with manganese-doped ZnS quantum dots (Mn-ZnS QDs) and 3-aminopropyl-triethoxysilane (APTES) as functional monomers and tetraethoxysilane (TEOS) as crosslinking agent was prepared for selective phosphorescence detection of 4-nitrophenol (4-NP).