Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion

<p>Abstract</p> <p>Background</p> <p>Tumor cell expression of Toll-like receptors (TLRs) can promote inflammation and cell survival in the tumor microenvironment. Toll-like receptor 4 (TLR4) signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. The expression of TLR4 in human breast cancer cell line MDA-MB-231 and its biological function in the development and progression of breast cancer have not been investigated. We sought to characterize the expression of TLR1-TLR10 in the established human breast cancer cell line MDA-MB-231, and to investigate the biological roles of TLR4 in breast cancer cells growth, survival, and its potential as a target for breast cancer therapy.</p> <p>Methods</p> <p>TLRs mRNA and protein expressions were detected in human breast cancer cell line MDA-MB-231 by RT-PCR, real-time PCR and flow cytometry (FCM). RNA interference was used to knockdown the expression of TLR4 in MDA-MB-231. MDA-MB-231 transfected with the vector pGenesil-1 and the vector containing a scrambled siRNA were as controls. Recombinant plasmids named TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA specific to TLR4 were transfected into human breast cancer cell line MDA-MB-231 with Lipfectamine™2000 reagent. TLR4 mRNA and protein expressions were investigated by RT-PCR, real-time PCR, FCM and immunofluorescence after silence. MTT analysis was performed to detect cell proliferation and FCM was used to detect the secretion of inflammatory cytokines in supernatant of transfected cells.</p> <p>Results</p> <p>The human breast cancer cell line MDA-MB-231 was found to express TLR1-TLR10 at both the mRNA and protein levels. TLR4 was found to be the highest expressed TLR in MDA-MB-231. TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA were found to significantly inhibit TLR4 expression in MDA-MB-231 at both mRNA and protein levels as compared to vector control(vector transfected cells). TLR4AsiRNA mediated the strongest effect. Knockdown of TLR4 gene in MDA-MB-231 resulted in a dramatic reduction of breast cancer cell viability. The cytokines which were secreted by the TLR4 silenced cells, such as IL-6 and IL-8, also decreased significantly as compared with vector control. No significant difference was observed in siRNA control (Recombinant plasmid named ScrambledsiRNA transfected cells) compared to vector control.</p> <p>Conclusions</p> <p>These studies identified the expression levels of multiple TLRs in human breast cancer cell line MDA-MB-231 and demonstrated that knockdown of TLR4 could actively inhibit proliferation and survival of breast cancer cells. Taken together, our results suggest RNAi-directed targeting of TLR4 may be a beneficial strategy for breast cancer therapy.</p

Changes of Microorganisms and Flavor Compounds in the Fourth Round Jiupei of Sauce-flavored Baijiu in Beijing

Sauce-flavor Baijiu shows a typical sauce flavor, with a delicate mouthfeel. Its fermentation process consists of seven cycles, and each cycle produces one kind of base liquor. The fourth cycle liquor has a rich flavor and excellent quality. During the fermentation process, microorganisms are in a dynamic state, while flavor substances differ. This study investigated the microbial changes of Jiupei in the fourth cycle and their impact on flavor substances. Species diversity analysis was conducted on the fourth cycle Jiupei sample using high-throughput sequencing. Flavor substances were analyzed using headspace solid-phase microextraction combined with gas chromatography-mass spectrometry. Results showed that the dominant bacteria in the Jiupei were Lactobacillus, Virgibacillus, and Kroppenstedtia, while dominant fungi were Thermoascus, Aspergillus, and Issatchenkia. The microbial community in the Jiupei showed significant dynamic changes during the later stage of fermentation. The Jiupei showed the richest variety of alcohol and ester substances at the beginning of fermentation, with the relative content of alcohol, ester, and acid compounds showing a pattern of increasing firstly and then gradually decreased during fermentation. This study conducted a correlation analysis between fungi and bacteria at the genus level and flavor substances, revealing that Monascus, Lactobacillus, and Wickerhamomyces were positively correlated with key flavor substances, such as ethyl acetate, ethyl lactate, and ethyl hexanoate, respectively. The data provided a basis for comparing the microorganisms and flavor substances in the fourth cycle of sauce-flavor Baijiu, and offered a theoretical basis for improving the quality of Baijiu

Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells

<p>Abstract</p> <p>Background</p> <p>Isothiocyanates are natural compounds found in consumable cruciferous vegetables. They have been shown to inhibit chemical carcinogenesis by a wide variety of chemical carcinogens in animal models. Recent studies have also shown that isothiocyanates have antitumor activity, inhibiting the growth of several types of cultured human cancer cells. Our previous study showed that PEITC inhibited human leukemia cells growth by inducing apoptosis. However, the effect of isothiocyanates on lung cancer cell metastasis has not been studied. In the present study, we investigated the inhibitory effects of BITC and PEITC on metastatic potential of highly metastatic human lung cancer L9981 cells.</p> <p>Methods</p> <p>Cell migration and invasion were measured by wound healing assay and transwell chemotaxis assay. Expression of metastasis-related genes was assessed by quantitative RT-PCR and Western blotting. The mechanisms of action were evaluated by flow cytometry, reporter assay and Western blotting.</p> <p>Results</p> <p>Our data showed that both BITC and PEITC inhibited L9981 cell growth in a dose-dependent manner, the IC50 values were 5.0 and 9.7 μM, respectively. Cell migrations were reduced to 8.1% and 16.5% of control, respectively; and cell invasions were reduced to 2.7% and 7.3% of control, respectively. Metastasis-related genes MMP-2, Twist and β-catenin were also modulated. BITC and PEITC inhibited cell survival signaling molecules Akt and NFκB activation. Moreover, BITC and PEITC increased ROS generation and caused GSH depletion. Pretreatment with NAC blocked BITC and PEITC induced ROS elevation and NFκB inhibition.</p> <p>Conclusion</p> <p>Our results indicated that BITC and PEITC suppress lung cancer cell metastasis potential by modulation of metastasis-related gene expression, inhibition of Akt/NFκB pathway. Induction of oxidative stress may play an important role.</p

Cascade self-splitting of a Hermite-cos-Gaussian correlated Schell-model beam

We propose a new kind of partially coherent beam with a nonconventional correlation function termed as Hermite-cos-Gaussian correlated Schell-model (HcGCSM) beam. The propagation properties of this novel model beam are investigated. It is found that the HcGCSM beam exhibits cascade self-splitting properties on propagation in free space, i.e., the initial single beam spot is proved to be successively split for two times during the whole propagation. Furthermore, we demonstrate that the cascade self-splitting phenomenon can be closely controlled through modulating the spectral degree of coherence of a HcGCSM beam in the source plane

Propagation Property of an Astigmatic sin–Gaussian Beam in a Strongly Nonlocal Nonlinear Media

Based on the Snyder and Mitchell model, a closed-form propagation expression of astigmatic sin-Gaussian beams through strongly nonlocal nonlinear media (SNNM) is derived. The evolutions of the intensity distributions and the corresponding wave front dislocations are discussed analytically and numerically. It is generally proved that the light field distribution varies periodically with the propagation distance. Furthermore, it is demonstrated that the astigmatism and edge dislocation nested in the initial sin-Gaussian beams greatly influence the pattern configurations and phase singularities during propagation. In particular, it is found that, when the beam parameters are properly selected, a vortex beam with perfect doughnut-shaped profile can be obtained for astigmatic sin-Gaussian beams with two-lobe pattern propagating in SNNM

Can Digital Inclusive Finance Improve the Financial Performance of SMEs?

Our paper takes the sample of listed companies from Shanghai and Shenzhen A-share SMEs and then theoretically analyzes and empirically tests the impact of digital inclusive finance on the financial performance of SMEs. The results show that financial performance of SMEs located in areas with a higher level of digital inclusive finance is significantly higher. Digital inclusive finance can play a role in expanding the scale of innovative investment, reducing the cost of debt financing and improving the ability of risk-taking, thereby strengthening the financial performance of SMEs. Our findings enrich the academic research on the topic of digital inclusive finance from the perspective of SMEs and provide suggestions to the government, banks and SMEs to continually implement the digital inclusive finance policy