Taurine (Tau) has been shown to possess cancer therapeutic effect through induction of apoptosis, while the underlying molecular mechanism of its anti-cancer effect is not well understood. PUMA (p53-upregulated modulator of apoptosis) plays an important role in the process of apoptosis induction in a variety of human tumor cells in both p53-dependent and -independent manners. However, whether PUMA is involved in the process of Tau-induced apoptosis in cancer cells has not been well studied. In the present study, we treated human colorectal cancer cells HT-29 (mutant p53) and LoVo (wild-type p53) with different concentrations of Tau, which led to the repression of cell proliferation and induction of apoptosis in both cell lines. Meanwhile, we also observed the increased expression of PUMA and high Bax/Bcl-2 ratios. To determine the role of PUMA in Tau-induced apoptosis, we used small interfering RNA interference to suppress PUMA expression. As a result, apoptosis was decreased in response to Tau treatment. All these results indicated that PUMA plays a critical role in Tau-induced apoptosis pathway in human colorectal cancer cells. Demonstration of the molecular mechanism involved in the anti-tumor effect of Tau may be useful in the therapeutic target selection for p53-deficient colorectal cancer.
Organic single-crystal films (OSCFs) provide an unprecedented opportunity for the development of new-generation organic single-crystal electronics. However, crystallization of organic films is normally governed by stochastic nucleation and incoherent growth, posing a formidable challenge to grow large-sized OSCFs. Here, an "orientation filter funnel" concept is presented for the scalable growth of OSCFs with well-aligned, singly orientated crystals. By rationally designing solvent wetting/dewetting patterns on the substrate, this approach can produce seed crystals with the same crystallographic orientation and then maintain epitaxial growth of these crystals, enabling the formation of large-area OSCFs. As a result, this unique concept for crystal growth not only enhances the average mobility of organic film by 4.5-fold but also improves its uniformity of electrical properties, with a low mobility variable coefficient of 9.8%, the new lowest record among organic devices. The method offers a general and scalable route to produce OSCFs toward real-word electronic applications.
Methamphetamine (METH), a psychostimulant, has the potential to cause neurodegeneration by targeting the cerebrum and cerebellum. It has been suggested that the NLRP3 inflammasome may be responsible for the neurotoxicity caused by METH. However, the role of NLRP3 in METH-induced cerebellar Purkinje cell (PC) degeneration and the underlying mechanism remain elusive. This study aims to determine the consequences of NLRP3 modulation and the underlying mechanism of chronic METH-induced cerebellar PC degeneration. In METH mice models, increased NLRP3 expression, PC degeneration, myelin sheath destruction, axon degeneration, glial cell activation, and motor coordination impairment were observed. Using the NLRP3 inhibitor MCC950, we found that inhibiting NLRP3 alleviated the above-mentioned motor deficits and cerebellar pathologies. Furthermore, decreased mature IL-1β expression mediated by Caspase 1 in the cerebellum may be associated with the neuroprotective effects of NLRP3 inflammasome inhibition. Collectively, these findings suggest that mature IL-1β secretion mediated by NLRP3-ASC-Caspase 1 may be a critical step in METH-induced cerebellar degeneration and highlight the neuroprotective properties of inflammasome inhibition in cerebellar degeneration.
Two-dimensional molecular crystals with a defined number of molecular layers were produced by a layer-defining strategy of crystal growth on a liquid substrate, reported by R. Li, W. Hu, et. al in their Communication on page 16082 ff. By controlling the spreading of the solution on the liquid surface, large-area quasi-freestanding two-dimensional molecular crystals can be obtained ranging from bulk size down to the monolayer limit. This method allows the layer-dependent optoelectronic properties of organic semiconductors to be probed.
The aim of the present study was to observe the effect and molecular mechanism of taurine (Tau) on the cell proliferation and apoptosis of human hepatocellular carcinoma (HHCC) HepG2 cells. HHCC HepG2 cells were used as target cells, and the cell survival rate was assessed using a multi-time-step method. The p53 upregulated modulator of apoptosis (PUMA) gene was transiently transfected by lipofection and subsequently silenced with specific small interfering (si)RNA. The cell apoptosis rate was detected by flow cytometry, and protein expression levels were analyzed with western blotting. Addition of 20-160 mM Tau was shown to have a significant inhibitory effect on cell proliferation, while promoting the induction of HHCC HepG2 cell apoptosis (P<0.05). Transfection of the PUMA gene significantly enhanced the ability of Tau to inhibit proliferation and induce apoptosis of HepG2 cells. In addition, transfection of the PUMA gene increased the protein expression of B-cell lymphoma-2-associated X and reduced the expression of B-cell lymphoma-2 (P<0.05). Silencing the PUMA gene with specific siRNA was demonstrated to significantly reduce the ability of Tau to inhibit proliferation and induce the apoptosis of HHCC HepG2 cells (P<0.01). Therefore, the PUMA gene was shown to have an important role in mechanism underlying the effect that Tau exerts on cell proliferation and apoptosis in HHCC HepG2 cells.
The content of nitrate nitrogen in soil directly reflects the short-term supply ability of soil nitrogen, which is the crucial factor affecting the growth of crops. For the correction factor method of ultraviolet spectrophotometry can't effectively remove the interference of nitrite, this paper proposes a dual wavelength of K ratio spectrophotometry to detect nitrate nitrogen in soil in order to effectively eliminate the interference of the nitrite. The spectrum scanning was made for soil extract obtained by saturated calcium sulfate solution, selecting 205 nm and 230 nm as measuring wavelength and reference wavelength, to determine the coefficient K. Furthermore, the linear regression equation of standard curve on the relationship between concentrations of nitrate nitrogen and the corrected absorbance could be derived by regression analysis. Therefore, the quantitative model of nitrate nitrogen was established using dual-wavelength of K ratio spectrophotometry. Compared with correction factor method of ultraviolet spectrophotometry by soil sample experiments, the fitting correlation coefficient (R2 = 0.9996) of this method is higher than the latter (R2 = 0.9988), which showed its repeatability precision was better than the latter and the feasibility and validity of this method were proved.
This study aims to investigate the effects of targeted regulation of Mst1 (Mammalian sterile 20-like kinase 1) expression on the proliferation and apoptosis of SW480 colorectal cancer cells and to elucidate the mechanisms underlying these effects. PolyJetTM in vitro DNA transfection reagent was used to transfect pEGFP-N1-Mst1 into SW480 colorectal cancer cells, and LipofectamineTM2000 was used to transfect Mst1-specific siRNA for the targeted silencing of Mst1. MTT assay was then performed to detect the survival rate of the cells, flow cytometry was used to determine apoptosis, and RT-qPCR and western blot were used to measure the mRNA and protein levels of Mst1, PUMA, p73, p53, YAP (Yes Associated Protein 1), and caspase-3. Compared with the control group, the p-EGFP-Mst1 and p-EGFPMst1+ 5-FU groups showed significantly higher rate of cell proliferation inhibition and apoptosis (P<0.05). The protein levels of MST1, Phospho-YAP1 (Ser127), P73, P53, PUMA, and Caspase-3 were significantly increased (P<0.05), while the protein levels of CTGF (Connective Tissue Growth Factor) and AREG (Amphiregulin) were significantly reduced (P<0.05). In the Mst1-siRNA group, the apoptosis rate was significantly decreased (P<0.01), cell proliferation was accelerated, p73, p53, and PUMA were downregulated, and CTGF, AREG, and YAP were upregulated. The targeted regulation of Mst1 expression significantly affected the proliferation and apoptosis of the SW480 cells. Thus, Mst1 has potential for use as a new target for the prevention and treatment of colorectal cancer.
A previous study by our group demonstrated that the expression levels of Notch 1 and Jagged 1 in bladder cancer cells was significantly lower compared with those in normal bladder mucosa, while the expression levels of Notch 1 and Jagged 1 in invasive bladder cancer were higher compared with those in superficial bladder cancer. The present study investigated the effect of the Notch signaling pathway on the drug resistance and invasiveness of bladder cancer cells. It was demonstrated that complete inhibition of the Notch signaling pathway induced significant morphological changes and inhibited cell proliferation and migration (P<0.05). Reverse transcription quantitative polymerase chain reaction and western blot analyses revealed that the mRNA and protein expression levels of E-cadherin were upregulated (P<0.05) and the mRNA and protein expression levels of N-cadherin, vimentin and α-smooth muscle actin were downregulated (P<0.05). The present study concluded that complete inhibition of the Notch signaling pathway inhibited cell proliferation and invasion, and reduced drug resistance in bladder cancer cells, a phenomenon which may be associated with the inhibition of the epithelial-mesenchymal transition.
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