Regulation of Long Non-Coding RNA-Dreh Involved in Proliferation and Migration of Hepatic Progenitor Cells during Liver Regeneration in Rats

Liver regeneration plays a significant role in protecting liver function after liver injury or chronic liver disease. Long non-coding RNAs (lncRNAs) are considered to be involved in the proliferation of hepatocytes and liver regeneration. Therefore, this study aimed to explore the effects of LncRNA-Dreh on the regulation of hepatic progenitor cells (HPCs) during liver regeneration in rats. Initially, the rat model of liver injury was established to investigate the effect of LncRNA-Dreh down-regulation on liver tissues of rats with liver injury. Subsequently, HPCs line WB-F344 cells were transfected with interference plasmid of LncRNA-Dreh and the expression of LncRNA-Dreh and Vimentin was detected. The proliferation and migration ability of WB-F344 cells, as well as the content of albumin (ALB) and alpha fetoprotein (AFP) in cell differentiation were then determined. Disorderly arranged structure of liver tissue, a large number of HPCs set portal area as center extended to hepatic lobule and ductular reaction were observed in liver tissues of rats with liver injury. The expression of LncRNA-Dreh decreased while Vimentin increased in liver tissues of rats with liver injury. Moreover, the proliferation and migration ability, expression of Vimentin and AFP in WB-F344 cells were increased after silencing of LncRNA-Dreh and ALB was decreased. Collectively, our findings demonstrate that inhibition of LncRNA-Dreh can enhance the proliferation and migration abilities of HPCs in liver regeneration but cause abnormal differentiation of HPCs

The Study of Bending and Twisting Input Modalities in Deformable Interfaces

The deformable input provides users with the ability of physical operation equipment to interact with the system. In order to facilitate further development in flexible display interactive technology, we devised FlexSheet, an input device that can simulate the deformation environment. This paper presents two forms of deformation input, bending and twisting, with regard to three selection techniques. We conduct a controlled experiment to select discrete targets by combining two input forms and three selection strategies, taking into account the influence of visual feedback. Further, we use the deformation angle to reflect the degree of deformation and map it to the experimental variables. In accordance with the experimental results, we analyze the experimental performance under three evaluation indexes and prove the viability of our selection technology in bending and twisting input modes. Finally, we provide suggestions on the control level in bending and twisting input modes, respectively

UPLC-Q-TOF/MS-Based Metabolomics Approach Reveals Osthole Intervention in Breast Cancer 4T1 Cells

Osthole (OST) is a simple coumarin derivative with pharmacological effects in many types of cancer cells. However, its role and its mechanism of action in breast cancer 4T1 cells remain unclear. In this study, we explored the effects and potential mechanisms of action of OST in 4T1 cells. The MTT, PI, and Annexin V-FITC/PI methods were used to evaluate the effects of OST-treated and untreated 4T1 cells on viability, cell cycle, and apoptosis, respectively. UPLC-Q-TOF/MS combined with multivariate data analysis was used to screen potential biomarkers relevant to the therapeutic mechanisms of OST. Additionally, mTOR, SREBP1, and FASN protein levels were detected using western blotting in OST-treated and untreated 4T1 cells. OST inhibited 4T1 cell proliferation, blocked the cells from remaining in S-phase, and induced apoptosis. In 4T1 cells, OST mainly affected the phospholipid biosynthesis, methyl histidine metabolism, pyrimidine metabolism, and β-oxidation of very long chain fatty acid pathways, suggesting that metabolic changes related to lipid metabolism-mediated signaling systems were the most influential pathways, possibly via inhibition of mTOR/SREBP1/FASN signaling. Our findings reveal biomarkers with potential therapeutic effects in breast cancer and provide insight into the therapeutic and metabolic mechanisms of OST in 4T1 cells

Improved synergistic anticancer action of quercetin and tamoxifen citrate supported by an electrospun complex nanostructure

A tri-fluid electrospinning process was successfully developed to prepare tri-chamber complex nanofibers. The core–shell and Janus structure were combined to form a delicate and complicated architecture for solving the problem of co-administration of quercetin and tamoxifen citrate, improving the oral bioavailability, and enhancing their synergistic anti-breast cancer actions. Scanning electron microscope, transmission electron microscope and confocal fluorescent microscopy images showed the complex structure of the designed nanofibers. Fourier transform infrared and X-ray diffraction analyses verified that the model drugs and the polymeric excipients had good compatibility and were presented in an amorphous state. The in vitro release study certified that the tri-chamber nanofibers facilitated the rapid release of quercetin compared with that of the crude drug (90% versus 38%) and the delayed and sustained release of tamoxifen citrate at the same time interval (decreased by 1.88 times). The in vivo pharmacokinetic and pharmacodynamic analysis verified that the tri-chamber nanofibers could result in increased oral bioavailability and enhanced synergistic anticancer action of quercetin and tamoxifen citrate. The findings proved that a new medicated drug delivery system with advanced dual-, time-, and target-specific drug release profiles was developed using the electrospun complex nanostructure

Higher Circulating Trimethylamine N-Oxide Aggravates Cognitive Impairment Probably via Downregulating Hippocampal SIRT1 in Vascular Dementia Rats

Oxidative stress and inflammation damage play pivotal roles in vascular dementia (VaD). Trimethylamine N-oxide (TMAO), an intestinal microbiota-stemming metabolite, was reported to promote inflammation and oxidative stress, involved in the etiology of several diseases. Still, these effects have not been investigated in VaD. Here, we tested whether pre-existing, circulating, high levels of TMAO could affect VaD-induced cognitive decline. TMAO (120 mg/kg) was given to rats for a total of 8 weeks, and these rats underwent a sham operation or bilateral common carotid artery (2VO) surgery after 4 weeks of treatment. Four weeks after surgery, the 2VO rats exhibited hippocampal-dependent cognitive function declines and synaptic plasticity dysfunction, accompanied by an increase in oxidative stress, neuroinflammation, and apoptosis. TMAO administration, which increased plasma and hippocampal TMAO at 4 weeks postoperatively, further aggravated these effects, resulting in exaggerated cognitive and synaptic plasticity impairment, though not within the Sham group. Moreover, TMAO treatment activated the NLRP3 inflammasome and decreased SIRT1 protein expression within the hippocampus. However, these effects of TMAO were significantly attenuated by the overexpression of SIRT1. Our findings suggest that TMAO increases oxidative stress-induced neuroinflammation and apoptosis by inhibiting the SIRT1 pathway, thereby exacerbating cognitive dysfunction and neuropathological changes in VaD rats

Polysaccharides from Chinese Herbal Lycium barbarum Induced Systemic and Local Immune Responses in H22 Tumor-Bearing Mice

Lycium barbarum polysaccharide (LBP) is isolated from the fruit of Chinese herbal Lycium barbarum. Previous studies had demonstrated that LBP could inhibit tumor growth and enhance the immunity in mice. However, the effect of LBP on systemic and local immune responses in vivo, especially on phenotypic and functional changes of T cells, is still largely unknown. In the present study, we investigated the effects of LBP on systemic and local T cell-dependent antitumor immune responses in H22 tumor-bearing mice. The results showed that LBP could inhibit the solid tumor growth in mice, but showed little effect on the body weight or spleen index. Furthermore, LBP could maintain high levels of T cells in peripheral blood (PB), tumor draining lymph node (TDLN), and tumor tissue, prevent the increase of Tregs while promote infiltration of CD8+ T cells in tumor tissue, inhibit the production of TGF-β1 and IL-10 in serum, decrease the exhaustion phenotype of T cells, and maintain cytotoxicity of lymphocytes. Taken together, our results demonstrated that LBP simultaneously induced systemic and local immune responses in H22 tumor-bearing mice by alleviating immunosuppression and maintaining antitumor immune responses in mice

Effects of Lycium barbarum polysaccharides with different molecular weights on function of RAW264.7 macrophages

The present study was aimed at investigating the effects of four LBP fractions with different molecular weights (MWs), designated LBP2, LBP3, LBP4 and LBP5, on RAW264.7 macrophages function. Results showed that LBP fractions could significantly enhance the expression of CD86 and MHC-II molecules on RAW264.7 macrophages. LBP3, LBP4 and LBP5 could enhance the production of ROS, NO, TNF-α and IL-6, and the phagocytosis of RAW264.7 macrophages. LBP2 with an MW of larger than 350 kDa could only enhance the secretion of TNF-α. LBP3 enhanced the RAW264.7 macrophages function in a dose-dependent manner and also enhanced the iNOS mRNA expression in the cells. These results demonstrated that the immunomodulatory activity of LBP on RAW264.7 macrophages was closely related to its MW. It indicated that fractions with an MW smaller than 350 kDa were the main active fractions of LBP in enhancing macrophages function

Toxic effects of amoxicillin on the photosystem II of Synechocystis sp characterized by a variety of in vivo chlorophyll fluorescence tests

Amoxicillin is one of the widely used antibiotics of environmental concern. This study shows that amoxicillin has toxic effects on the photosynthesis of Synechocystis sp. Its inhibitory effects on photosystem II (PSII) of Synechocystis sp. were investigated by using a variety of in vivo chlorophyll fluorescence tests. The inhibitory effects of amoxicillin on PSII activity of Synechocystis sp. are concentration-dependent. Amoxicillin exposure leads to slowing down of electron transport on both donor side and acceptor side and causes accumulation of P680(+). QA(-) reoxidation test revealed that amoxicillin hinders electron transfer from QA(-) to QB/QB(-) and more QA(-) is oxidized through S-2(Q(A)Q(B))(-) charge recombination. Analysis of PSII heterogeneity demonstrated that an exposure to amoxicillin increases the proportion of inactive PSII (PSIIx) centers and the proportion of PSII centers with small antenna (PSII beta). These changes finally result in deterioration of full photosynthesis performance. (C) 2008 Elsevier B.V. All rights reserved

Effects of pH and salinity on adsorption of hypersaline photosynthetic microbial mat exopolymers to goethite:A study using a quartz crystal microbalance and fluorescence spectroscopy

<p>Salinity and pH are two water chemical factors that vary drastically—seasonally or daily—in a variety of aquatic environments. Drastic change of salinity and pH may have a significant impact on adsorption of microbial extracellular polymers (EPS) to sediment minerals and thus influence many other important elemental geochemical processes. However, how salinity and pH changes affect EPS adsorption to minerals is poorly known. In the present study, adsorption of EPS from a hypersaline microbial mat to goethite at different pH values (4, 7 and 10) and salinity (0.15‰, 35‰ and 70‰) was monitored online using a quartz crystal microbalance (QCM) with EEM fluorescence spectroscopy as a complementary method. The adsorption kinetics were well described by an exponential function. The adsorption capacity of EPS to goethite significantly increased as the pH and salinity increased. The pH and salinity dependence of EPS adsorption to goethite is of great importance for understanding the environmental geochemistry of heavy metals in aquatic environments. In inland lakes and estuary zones, the seasonal or daily pulse of hydrological events will drastically alter water salinity and pH and consequently exert significant influences on the mobility, chemical species and ecotoxicity of heavy metals through the EPS pathway. It is necessary to systematically investigate the geochemical behavior of EPS in such dynamic aquatic environments and their potential effects on other geochemical processes.</p