Signal transducer and activator of transcription 3 (STAT3) was reported to be involved in adipogenesis. However, the regulating mechanism of STAT3 remains unclear. The present results showed that STAT3 was activated within 2-h adipogenic induction, in which the phosphorylated STAT3 translocated from cytoplasm to the nucleus. In addition, we detected Janus kinase2 (JAK2) acted upstream of the STAT3 activation at the early stage of adipogenesis. Accordingly, the JAK2 inhibitor AG490 and siRNAs led to the partial inhibition of the STAT3 activation, and the inhibition of 3T3-L1 adipocyte differentiation. Furthermore, the results based on luciferase, chromatin immunoprecipitation, and gel shift approaches indicated that STAT3 could regulate the transcription of C/EBPβ by binding the distal region of C/EBPβ promoter at the early stage of adipogenesis. Collectively, our findings reveal that JAK2/STAT3 pathway is involved in the early stage of 3T3-L1 adipocyte differentiation though regulating the C/EBPβ transcription.
Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation of 3T3-L1 cells requires two processes: the licensing of an adipogenesis gene-expression program within a particular growth-arrest stage, i.e., the contact-inhibition stage, and then the execution of this program in a cell-cycle-independent manner, by which the licensed progenitors are differentiated into adipocytes in the presence of inducing factors. Our results showed that differentiation licensing of 3T3-L1 cells during the contact-inhibition stage involved epigenetic modifications such as DNA methylation and histone modifications, whereas disturbing these epigenetic modifications by DNA methylation inhibitors or RNAi during the contact-inhibition stage significantly reduced adipogenesis efficiency. More importantly, when these licensed 3T3-L1 cells were re-cultured under non-differentiating conditions or treated only with insulin, this adipogenesis commitment could be maintained from one cell generation to the next, whereby the licensed program could be activated in a cell-cycle-independent manner once these cells were subjected to adipogenesis-inducing conditions. This result suggests that differentiation licensing and differentiation execution can be uncoupled and disparately linked to cell proliferation. Our findings deliver a new concept that cell-fate decision can be subdivided into at least two stages, licensing and execution, which might have different regulatory relationships with cell proliferation. In addition, this new concept may provide a clue for developing new strategies against obesity.
Since emulsifying properties are important functional properties of soy protein, many physical, chemical, and enzymatic methods have been applied to treat soy protein to improve emulsifying properties. In this study, we investigated the effects of swirling cavitation at different pressures and for different times on emulsifying and physicochemical properties of soy protein isolate (SPI). The SPI treated with swirling cavitation showed a significant decrease in particle size and increase in solubility. Emulsions formed from treated SPI had higher emulsifying activity and emulsifying stability indexes, smaller oil droplet sizes, lower flocculation indexes, higher adsorbed proteins, lower interfacial protein concentrations, and lower creaming indexes than those formed from untreated SPI, indicating that swirling cavitation improved the emulsifying properties of the SPI. Furthermore, swirling cavitation treatment significantly enhanced the surface hydrophobicity, altered the disulfide bond and exposed sulfhydryl group contents of the SPI. The secondary structure of the SPI was also influenced by swirling cavitation, with an increase in β-sheet content and a decrease in α-helix, β-turn, and random coil contents. In addition, several significant correlations between physicochemical and emulsifying properties were revealed by Pearson correlation analysis, suggesting that the physicochemical changes observed in treated SPI, including the decreased particle size, increased solubility and surface hydrophobicity, and enhanced β-sheet formation, may explain the improved emulsifying properties of the isolate. Thus, our findings implied that swirling cavitation treatment may be an effective technique to improve the emulsifying properties of SPI.
Stereotactic body radiotherapy (SBRT) has emerged as a standard treatment for non-small-cell lung cancer. However, its therapeutic advantages are limited with the development of SBRT resistance. The SBRT-resistant cell lines (A549/IR and H1975/IR) were established after exposure with hypofractionated irradiation. The differential lncRNAs were screened by microarray assay, then the expression was detected in LUAD tumor tissues and cell lines by qPCR. The influence on radiation response was assessed via in vitro and in vivo assays, and autophagy levels were evaluated by western blot and transmission electron microscopy. Bioinformatics prediction and rescue experiments were used to identify the pathways underlying SBRT resistance. High expression of KCNQ1OT1 was identified in LUAD SBRT-resistant cells and tissues, positively associated with a large tumor, advanced clinical stage, and a lower response rate to concurrent therapy. KCNQ1OT1 depletion significantly resensitized A549/IR and H1975/IR cells to radiation by inhibiting autophagy, which could be attenuated by miR-372-3p knockdown. Furthermore, autophagy-related 5 (ATG5) and autophagy-related 12 (ATG12) were confirmed as direct targets of miR-372-3p. Restoration of either ATG5 or ATG12 abrogated miR-372-3p-mediated autophagy inhibition and radiosensitivity. Our data describe that KCNQ1OT1 is responsible for SBRT resistance in LUAD through induction of ATG5- and ATG12-dependent autophagy via sponging miR-372-3p, which would be a potential strategy to enhance the antitumor effects of radiotherapy in LUAD.
Background: Fibrinogen concentrations and the monocyte-to-lymphocyte ratio (FC-MLR) are associated with progression and outcomes of many malignancies. This study aimed to assess the clinical and prognostic significance of the combination of plasma FC-MLR in patients with ovarian cancer. Methods: A total of 155 patients with epithelial ovarian cancer (EOC) and 102 patients with benign gynecological disease were retrospectively reviewed. The clinical and pathological data of all patients with EOC were analyzed. Plasma fibrinogen concentrations and the white blood cell (WBC) count were measured to calculate the MLR and neutrophil-to-lymphocyte ratio (NLR). Furthermore, the association of fibrinogen concentrations, the MLR, and FC-MLR with tumor stage, lymphatic and venous metastasis, and 5-year survival was assessed. Regression analysis was performed to evaluate the risk factors for progression of EOC. Receiver operating characteristic (ROC) curves were constructed to assess the prognostic power of plasma fibrinogen concentrations, the MLR, and FC-MLR, and to determine the optimal cutoff values of fibrinogen and the MLR. On the basis of the cutoff values, patients with EOC were divided into three groups: no abnormality, either increased, and both increased groups, respectively. The effect of FC-MLR on overall survival was calculated by the Kaplan-Meier method and compared by the log-rank test in the three groups. Results: Patients with EOC had higher fibrinogen concentrations and a higher MLR than did controls (both P<0.01), and FC-MLR was closely associated with tumor stage and lymphatic and venous metastasis (all P<0.001). Furthermore, FC-MLR was an independent risk factor for progression of EOC (OR =8.985; 95% CI: 4.912-27.166; P<0.001), and patients with high fibrinogen concentrations and a high MLR showed a lower 5-year survival rate (P<0.001). Conclusions: FC-MLR may be used as a predictor of tumor progression and prognosis for ovarian cancer.
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