Accumulating evidence has indicated that garlic consumption may reduce the risk of developing several types of cancer, and extensive studies have revealed the effects of its bioactive component, ...diallyl trisulfide (DATS), on the proliferation and apoptosis of tumor cells. The present study was undertaken to examine whether DATS affects hematogenous metastasis. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we attempted to demonstrate the role of DATS in the metastatic behavior of MDA-MB-231 human breast cancer cells, which were co-incubated with activated platelets. Indeed, our data indicated that DATS significantly blocked platelet activation and aggregation induced by platelet-activating factor (PAF), and decreased the production of thromboxane B2 (TXB2). It was also found that DATS suppressed the migration and invasion of MDA-MB-231 cells in the presence of platelets activated by PAF in vitro in a dose-dependent manner. Furthermore, our results revealed thaat the release of activated TGF-β1 in the platelet-tumor cell system was markedly attenuated by DATS. Therefore, our findings strongly suggest that the diverse pharmacological activities of DATS are at least partially reflected by the interruption of the activated platelets-mediated metastasis of breast cancer cells.
Radix et Rhizoma Ginseng (thereafter called ginseng) has been used as a medicinal herb for thousands of years to maintain people's physical vitality and is also a non–organ-specific cancer preventive ...and therapeutic traditional medicine in several epidemiologic and preclinical studies. Owing to few toxic side effects and strong enhancement on body immunity, ginseng has admirable application potential and value in cancer chemoprevention. The study aims at investigating the chemopreventive effects of ginseng on cutaneous carcinoma and the underlying mechanisms.
The mouse skin cancer model was induced by 7,12-dimethylbenzaanthracene/12-O-tetradecanoylphorbol-13-acetate. Ultraperformance liquid chromatography/mass spectrometry was used for identifying various ginsenosides, the main active ingredients of ginseng. Comprehensive approaches (including network pharmacology, bioinformatics, and experimental verification) were used to explore the potential targets of ginseng.
Ginseng treatment inhibited cutaneous carcinoma in terms of initiation and promotion. The content of Rb1, Rb2, Rc, and Rd ginsenosides was the highest in both mouse blood and skin tissues. Ginseng and its active components well maintained the redox homeostasis and modulated the immune response in the model. Specifically, ginseng treatment inhibited the initiation of skin cancer by enhancing T-cell–mediated immune response through upregulating HSP27 expression and inhibited the promotion of skin cancer by maintaining cellular redox homeostasis through promoting nuclear translocation of Nrf2.
According to the study results, ginseng can be potentially used for cutaneous carcinoma as a chemopreventive agent by enhancing cell-mediated immunity and maintaining redox homeostasis with multiple components, targets, and links.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. ...Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.
A hepatocellular carcinoma (HCC)-on-a-chip was developed to mimic liver cancer and critical events, including tumor cell proliferation, endothelial cell invasion, tumor cell drug resistance, NK cell infiltration and exhaustion were assessed. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Financial literacy is becoming an increasingly important policy consideration, yet its determinants are still underexplored. From the theoretical perspective of 'learning by doing', the effect of ...homeownership on financial literacy in urban China is identified by the instrumental variable strategy. First, the borrowing experience to purchase a home can awaken homeowners to develop basic financial knowledge, but the resulting debt burden constrains homeowners from participating in the financial market, crowding out their access to advanced financial skills. Second, the growth in home equity wealth induces homeowners pledge high-value properties as collateral and invest in more homes, in which case the collateralizing experience facilities the advancement of basic finance literacy, while locking the asset portfolio in the housing sector hinders homeowners from learning advanced financial skills. Moreover, the specific kind of financial literacy that homeowners show an advantage in differs depending on their income. These findings cast a new light on understanding the return of housing property to family financial affairs.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution. Herein, we cultured primary thymic stromal cells (TSCs), used rosiglitazone, a potent peroxisome ...proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation, and investigated the differentially expressed genes during adipogenic differentiation by using RNA-sequencing analysis. Furthermore, the effects of Notch1 on rosiglitazone-induced adipogenic differentiation of TSCs as well as the underlying mechanisms were also investigated. As a result, we identified a total of 1737 differentially expressed genes, among which 965 genes were up-regulated and 772 genes were down-regulated in rosiglitazone-treated cells compared with control cells. Gene ontology (GO) enrichment analysis showed that the GO terms were enriched in metabolic process, intracellular, and protein binding. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that a number of pathways, including ubiquitin mediated proteolysis, PPAR signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway were predominantly over-represented. Meanwhile, overexpression of Notch1 suppressed and inhibition of Notch1 promoted rosiglitazone-induced adipogenic differentiation in TSCs, and the pro-adipogenic effects of the Notch inhibitor DAPT were associated with the activation of autophagy. Taken together, our results suggest that Notch1 is a key regulator in thymic adipogenesis and may serve as a potential target to hinder thymic adiposity in age-related thymic involution.
Adipocyte accumulation is a predominant feature of age-related thymic involution, but the mechanisms responsible for thymic adipogenesis remain to be elucidated. The aim of this study was to identify ...key regulators in thymic adipogenesis. We used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation of OP9-DL1 cells, and investigated the differentially expressed proteins during adipogenic differentiation by using label-free quantitative proteomics. Furthermore, the effects of transforming growth factor β1 (TGF-β1) on rosiglitazone-induced adipogenic differentiation of OP9-DL1 cells as well as the underlying mechanisms were also investigated.
Proteomic analysis identified 139 proteins differed significantly in rosiglitazone-treated cells compared with dimethyl sulphoxide (DMSO)-treated cells. Rosiglitazone-induced adipogenic differentiation was inhibited by TGF-β1 treatment in OP9-DL1 cells and primary thymic stromal cells. Real-time PCR analysis showed significant increases in PPARγ and fatty acid binding protein 4 mRNA levels in rosiglitazone-treated cells, which were inhibited by TGF-β1 treatment. TGF-β1 down-regulated PPARγ expression at both mRNA and protein levels in OP9-DL1 cells. Chromatin immunoprecipitation analysis demonstrated that TGF-β1 enhanced the binding of Smad2/3 and histone deacetylase 1, but reduced the binding of H3K14ac to the promoter of PPARγ gene. TGF-β1 partially reversed the inhibitory effects of rosiglitazone on the expression of Axin2 and β-catenin protein levels. TGF-β1 inhibited rosiglitazone-induced adipogenic transformation in OP9-DL1 cells by down-regulation of PPARγ and activation of the canonical Wnt/β-catenin signaling pathway.
Taken together, activation of TGF-β pathway may serve as a useful strategy to prevent thymic adiposity in age-related thymic involution.
The structure of thermoelectric materials largely determines the thermoelectric characteristics. Hence, a better understanding of the details of the structural transformation process/conditions can ...open doors for new applications. In this study, the structural transformation of PbTe (a typical thermoelectric material) is studied at the atomic scale, and both nucleation and growth are analyzed. We found that the phase transition mainly occurs at the surface of the material, and it is mainly determined by the surface energy and the degree of freedom the atoms have. After exposure to an electron beam and high temperature, high-density crystal-nuclei appear on the surface, which continue to grow into large particles. The particle formation is consistent with the known oriented-attachment growth mode. In addition, the geometric structure changes during the transformation process. The growth of nanoparticles is largely determined by the van der Waals force, due to which adjacent particles gradually move closer. During this movement, as the relative position of the particles changes, the direction of the interaction force changes too, which causes the particles to rotate by a certain angle.
The detection and monitoring of toxic and harmful gases play a vital role in environmental protection, human health, and industrial and agricultural production. However, it is still challenging to ...develop gas sensors for the detection of toxic and harmful gases with high sensitivity, good recovery and excellent selectivity. In this study, WO3/Al2O3/graphite composite materials were used for an MEMS 2-CEES gas sensor (dichlorodiethyl sulfide simulation), and the corresponding sensing properties were explored. The experimental results show that when the working temperature is 340 °C, the response of the sensor to 2-CEES gas with a concentration of 5.70 ppm is 69%, the response time is 5 s and the recovery time is 42 s. The sensor also has the advantages of long-term stability and high selectivity. Furthermore, the MEMS gas sensor array based on WO3/Al2O3/graphite composite materials has been achieved and also exhibits excellent sensing performance. Overall, this study provides a strategy for realizing high-performance dichlorodiethyl sulfide gas sensors.
Pancreatic ductal adenocarcinoma has the worst prognosis of any gastrointestinal cancer, with the mortality approaching the incidence. Early detection is crucial for improving patient prognosis. We ...therefore performed a meta-analysis to assess the diagnostic performance of MUC1 for pancreatic ductal adenocarcinoma (PDAC). A comprehensive search was performed to retrieve relevant studies on detecting immunohistochemical expression of MUC1 in the diagnosis of PDAC. Data on accuracy of included studies were extracted for further heterogeneity exploring, statistical pooling, and SROC (summary receiver operating characteristics) analyzing using the Meta-DiSc 1.4 and STATA 12.0 software. Seventeen studies were se1ected with 1,363 patients involved. The heterogeneity (except for threshold effect) was found in these studies. The pooled sensitivity and specificity were 0.83 (95 % confidence interval (CI), 0.81–0.86) and 0.63 (95 % CI, 0.59–0.66), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.02 (95 % CI, 1.95–4.70) and 0.21 (95 % CI, 0.13–0.32), respectively. The pooled diagnostic odds ratio (DOR) was 20.44 (95 % CI, 9.53–43.85). The area under of SROC curve was 0.8879 and the
Q
index was 0.8185. This meta-analysis indicates that MUC1 assay plays an important role in the diagnosis of PDAC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ