Search

Radon is a naturally occurring radioactive gas and considered as a serious carcinogen to humans. Continuous radioactive decay of this gas emits high-energy alpha particles. Long-term radon exposure induces oxidative stress and inflammatory response, which results in chronic lung diseases. However, biological effects after radon exposure in other organs have been rarely reported. As the outermost organ of the human body, the skin suffers from environmental damage to agents such as air pollution. Epidemiological studies indicated that areas with high level of radon had a high incidence of skin cancer. However, whether radon exposure induces skin damage has not been reported yet. In this study, we established a radon-exposed mouse model and found that radon exposure affected the structure of skin tissues, which was manifested by inflammatory cell infiltration and skin atrophy. Using proteomic approach, we found 45 preferentially expressed proteins in 60 Working Level Months (WLM) group and 314 preferentially expressed proteins in 120 WLM group from radon-exposed skin tissues. Through microRNA (miRNA) sequencing profiling analysis, 57 dysregulated miRNAs were screened between the control and radon-treated mouse skin. By integrating the dysregulated proteins and miRNAs, radon-induced fatty acid synthase (FASN) was investigated in greater detail. Results showed that FASN was regulated by miR-206-3p and miR-378a-3p and involved in the pathogenesis of radon-induced skin damage. Overexpression of FASN inhibited the proliferation, and induced in WS1 cells. Our present findings illustrate the molecular change during radon-induced skin damage and the potential role of FASN during this process.

Non-alcoholic fatty liver disease (NAFLD) has become a globally rising issue that can cause liver-related morbidity and mortality. Recent studies have revealed that a high-fat diet (HFD) highly contributes to the prevalence and progression of NAFLD via impacting gut microbiota and lipid metabolism signal pathways. Resveratrol (RSV), a natural bioactive compound, has exhibited potential for preventing and alleviating NAFLD. However, due to the poor bioavailability of RSV, its strengths and underlying mechanisms for NAFLD therapeutic potential are poorly understood. To address this, we utilized Hydroxypropyl-beta-Cyclodextrin (HBC) to encapsulate RSV to enhance its water solubility and conducted prevention and intervention experiments in HFD-fed mice. The results showed that the HBC has significantly enhanced the water solubility of RSV by 250-fold and the HBC-RSV better prevented and alleviated the liver steatosis, obesity and abnormal lipid metabolism induced by HFD than RSV alone. Meanwhile, combining HFD and HBC-RSV or RSV prevented HFD mice progressing to NAFLD. Besides, further investigation indicated that RSV could resist liver injury and obesity by modulating gut microbiota, raising the levels of short-chain fatty acids (SCFAs) and activating AMP-activated protein kinase (AMPK) signaling pathway. The activated pathway down-regulated sterol receptor element binding protein 1c (SREBP1c) and acetyl-coenzyme A carboxylase (ACC) to decrease lipid synthesis and up-regulated peroxisome proliferators-activated receptorα (PPARα) to promote the fatty acid oxidation, thus preventing NAFLD. Our findings suggested that water solubility-enhanced RSV beneficially modulated gut microbiota, altered gut microbiota-derived SCFAs, and activated lipid metabolism regulatory pathways, providing potential for NAFLD prevention and alleviation.

Reaction of 4,4′,4″-nitrilotribenzoic acid (H3L), a C3-symmetric ligand, with the divalent Co(II) salt Co(NO3)2·6H2O in the present of the N-donor ligand 1,2-di(4-pyridyl)ethylene (DPE) affords a new mixed-ligand coordination polymer with the chemical formula of [Co3(TNB)(DPE)2]·2H2O·DMF (1). In this study, CCK-8 assay was used to determine the effect of novel compound on proliferation of gastric cancer cells. The VEGF signaling pathway in gastric cancer cells was determined through employing real-time PCR after treatment of the above complex. Further, molecular docking simulation confirmed that the biological activity was coming from the carboxyl groups through the hydrogen bonding interactions with the receptor protein, the pyridine group only bonded with the Co ion for the formation of the Co complex.

[Display omitted]

The protein tyrosine kinase Syk plays a central role in Fcγ receptor–mediated phagocytosis in the adaptive immune system. We show here that Syk also plays an essential role in complement-mediated phagocytosis in innate immunity. Macrophage-like differentiated HL60 cells and C3bi-opsonized zymosan comprised the pathogen-phagocyte system. C3bi-opsonized zymosan particles promptly attached to the cells and were subsequently engulfed via complement receptor 3. During this process, Syk became tyrosine phosphorylated and accumulated around the nascent phagosomes. The transfer of Syk-siRNA or dominant-negative Syk (DN-Syk) into HL60 cells resulted in impaired phagocytosis. Quenching assays using fluorescent zymosan revealed that most of the attached zymosan particles were located inside parental HL60 cells, whereas few were ingested by the mutant cells. These data indicated that Syk is required for the engulfment of C3bi-opsonized zymosan. During C3bi-zymosan–induced phagocytosis, actin accumulation occurred around phagosomes and was followed by depolymerization, and further RhoA was activated together with tyrosine phosphorylation of Vav. These responses including the actin remodeling were suppressed in Syk-siRNA– or DN-Syk–expressing cells. Our results demonstrated that Syk plays an indispensable role in complement-mediated phagocytosis by regulating both actin dynamics and the RhoA activation pathway and that these functions of Syk lead to phagosome formation and pathogen engulfment.

The protein tyrosine kinase Syk plays a central role in Fcγ receptor–mediated phagocytosis in the adaptive immune system. We show here that Syk also plays an essential role in complement-mediated phagocytosis in innate immunity. Macrophage-like differentiated HL60 cells and C3bi-opsonized zymosan comprised the pathogen-phagocyte system. C3bi-opsonized zymosan particles promptly attached to the cells and were subsequently engulfed via complement receptor 3. During this process, Syk became tyrosine phosphorylated and accumulated around the nascent phagosomes. The transfer of Syk-siRNA or dominant-negative Syk (DN-Syk) into HL60 cells resulted in impaired phagocytosis. Quenching assays using fluorescent zymosan revealed that most of the attached zymosan particles were located inside parental HL60 cells, whereas few were ingested by the mutant cells. These data indicated that Syk is required for the engulfment of C3bi-opsonized zymosan. During C3bi-zymosan–induced phagocytosis, actin accumulation occurred around phagosomes and was followed by depolymerization, and further RhoA was activated together with tyrosine phosphorylation of Vav. These responses including the actin remodeling were suppressed in Syk-siRNA– or DN-Syk–expressing cells. Our results demonstrated that Syk plays an indispensable role in complement-mediated phagocytosis by regulating both actin dynamics and the RhoA activation pathway and that these functions of Syk lead to phagosome formation and pathogen engulfment.

Aiming at the optimal design and analysis of stiffened panels, this paper proposes a new algorithm considering the torsion of supporting stiffeners on axial load carrying capacity. By defining three dimensionless factors: relative bearing capacity, relative transverse elastic stiffness and relative torsional elastic stiffness, the response surface of load-bearing capacity versus two kinds of elastic stiffness is obtained. Based on genetic algorithm, a lightweight optimization model for structure layout and section parameters is established. A certain stiffened panel is optimized on this basis, and the matching design relationship between two kinds of stiffeners is summarized.

A protein-tyrosine kinase, Syk plays a central role in Fc-gamma receptor-mediated phagocytosis in the adaptive immune system. Here we show that Syk also makes an essential role in compliment-mediated phagocytosis in innate immunity. For this purpose, HL60 cells induced to macrophage-like with vitamin D3 and TPA and C3bi-opsonized zymosan were used as the pathogen-phagocyte system. Time-lapse microscopic observation revealed that C3bi-opsonized zymosan particles were promptly attached to and sucked into the cells but non-opsonized zymosan was not, and therefore it was indicated that our phagocytosis system is mediated by the complement receptor 3 (CR3). Syk was tyrosine-phosphorylated by the treatment with C3bi-opsonized zymosan and marked accumulation of Syk was detected around the newly forming phagosomes. To further investigate the effect of Syk on complement-mediated phagocytosis, Syk-siRNA or dominant-negative Syk (DN-Syk) was introduced into HL60 cells. Quantitative analysis by flow cytometry showed that phagocytosis was severely impaired in DN-Syk or Syk-siRNA expressing HL60 cells. To determine whether the impaired capture of zymosan is due to reduced binding to CR3 or reduced engulfment after binding, the cells were treated with a quenching reagent which discriminates fluorescent zymosan particles between inside and outside the cells. In the parental HL60 cells most of the attached zymosan particles were inside the cells, while few particles were ingested in the case of DN-Syk or Syk-siRNA expressing HL60 cells. These data indicated that Syk is required for engulfment of C3bi-opsonized zymosan but not for attachment of zymosan to CR3. To clarify the molecular mechanism how Syk affects the phagosome formation and its engulfment, the behavior of F-actin was searched microscopically. At the early stage of complement-mediated phagocytosis, marked accumulation of F-actin occurred around each phagosome and was followed by rapid depolymerization in the parental HL60 cells. In contrast, phagosomes surrounded by the accumulated actin were significantly decreased in DN-Syk or Syk-siRNA expresssing cells. These results indicate that Syk promotes actin assembly around phagosomes prior to engulfment at the early stage of the phagocytosis. As for the analysis of the downstream pathway of Syk in our phagocytosis system, RhoA-signaling was investigated. Vav-RhoA pathway was activated in HL60 cells but transfer of DN-Syk or Syk-siRNA into HL60 cells reduced the activation of Vav-RhoA signaling. Therefore Syk may act as an activator of the RhoA-pathway in phagocytosis. Our results demonstrate that Syk is required for complement-mediated phagocytosis by regulating both actin accumulation around phagosomes and RhoA-signaling harmonically and finally leads to phagosome formation and its engulfment.

A protein-tyrosine kinase, Syk plays a central role in Fc-gamma receptor-mediated phagocytosis in the adaptive immune system. Here we show that Syk also makes an essential role in compliment-mediated phagocytosis in innate immunity. For this purpose, HL60 cells induced to macrophage-like with vitamin D3 and TPA and C3bi-opsonized zymosan were used as the pathogen-phagocyte system. Time-lapse microscopic observation revealed that C3bi-opsonized zymosan particles were promptly attached to and sucked into the cells but non-opsonized zymosan was not, and therefore it was indicated that our phagocytosis system is mediated by the complement receptor 3 (CR3). Syk was tyrosine-phosphorylated by the treatment with C3bi-opsonized zymosan and marked accumulation of Syk was detected around the newly forming phagosomes. To further investigate the effect of Syk on complement-mediated phagocytosis, Syk-siRNA or dominant-negative Syk (DN-Syk) was introduced into HL60 cells. Quantitative analysis by flow cytometry showed that phagocytosis was severely impaired in DN-Syk or Syk-siRNA expressing HL60 cells. To determine whether the impaired capture of zymosan is due to reduced binding to CR3 or reduced engulfment after binding, the cells were treated with a quenching reagent which discriminates fluorescent zymosan particles between inside and outside the cells. In the parental HL60 cells most of the attached zymosan particles were inside the cells, while few particles were ingested in the case of DN-Syk or Syk-siRNA expressing HL60 cells. These data indicated that Syk is required for engulfment of C3bi-opsonized zymosan but not for attachment of zymosan to CR3. To clarify the molecular mechanism how Syk affects the phagosome formation and its engulfment, the behavior of F-actin was searched microscopically. At the early stage of complement-mediated phagocytosis, marked accumulation of F-actin occurred around each phagosome and was followed by rapid depolymerization in the parental HL60 cells. In contrast, phagosomes surrounded by the accumulated actin were significantly decreased in DN-Syk or Syk-siRNA expresssing cells. These results indicate that Syk promotes actin assembly around phagosomes prior to engulfment at the early stage of the phagocytosis. As for the analysis of the downstream pathway of Syk in our phagocytosis system, RhoA-signaling was investigated. Vav-RhoA pathway was activated in HL60 cells but transfer of DN-Syk or Syk-siRNA into HL60 cells reduced the activation of Vav-RhoA signaling. Therefore Syk may act as an activator of the RhoA-pathway in phagocytosis.