Tumor initiation, progression, and response to therapies depend to a great extent on interactions between malignant cells and the tumor microenvironment (TME), which denotes the ...cancerous/non-cancerous cells, cytokines, chemokines, and various other factors around tumors. Cancer cells as well as stroma cells can not only obtain adaption to the TME but also sculpt their microenvironment through a series of signaling pathways. The post-translational modification (PTM) of eukaryotic cells by small ubiquitin-related modifier (SUMO) proteins is now recognized as a key flexible pathway. Proteins involved in tumorigenesis guiding several biological processes including chromatin organization, DNA repair, transcription, protein trafficking, and signal conduction rely on SUMOylation. The purpose of this review is to explore the role that SUMOylation plays in the TME formation and reprogramming, emphasize the importance of targeting SUMOylation to intervene in the TME and discuss the potential of SUMOylation inhibitors (SUMOi) in ameliorating tumor prognosis.
Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the ...progression of gastric cancer, among which m
6
A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan–Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m
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A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m
6
A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.
There is a practical motivation for correlating different types of microscopy for revealing complementary information of ultrastructures with resolution beyond the diffraction limit. The correlative ...microscopy strategy based on the combination of super-resolution fluorescence imaging with atomic force microscopy (AFM) is expected to provide both the specificity and three-dimensional structural information of nanomaterials. Herein we synthesized a dual-alternating-color photoswitchable fluorescent probe based on a naphthalimide-spiropyran dyad (NI-SP) and explored the capability of such correlative microscopy for visualizing nanostructures with complex structural hierarchy. NI-SP underwent reversible photoswitching between green and red fluorescence based on a reversible photochemical reaction and such reaction-linked correlation between two distinct types of fluorescence signals intrinsically enabled mutual authentication in super-resolution fluorescence imaging. Additionally, such correlative microscopy also demonstrated mutual complementation between different pieces of structural information of the target acquired via fluorescence imaging and AFM, respectively, in which the former reveals spatial distribution of fluorescent dyes in the nanoscale polymer fibroid micelles while the latter maps the topographical structure of the target with complex structural hierarchy. The results obtained in this work proclaimed that the combination of such correlative microscopy with our NI-SP probe is an effective modality for ultrastructural analysis and has future applications in various complex systems such as tissue/organ imaging.
CD47 serves as a ligand for signaling regulatory protein α (SIRPα) and as a receptor for thrombospondin‐1 (TSP‐1). Although CD47, TSP‐1, and SIRPα are thought to be involved in the clearance of aged ...red blood cells (RBCs), aging‐associated changes in the expression and interaction of these molecules on RBCs have been elusive. Using direct stochastic optical reconstruction microscopy (dSTORM)‐based imaging and quantitative analysis, we can report that CD47 molecules on young RBCs reside as nanoclusters with little binding to TSP‐1, suggesting a minimal role for TSP‐1/CD47 signaling in normal RBCs. On aged RBCs, CD47 molecules decreased in number but formed bigger and denser clusters, with increased ability to bind TSP‐1. Exposure of aged RBCs to TSP‐1 resulted in a further increase in the size of CD47 clusters via a lipid raft‐dependent mechanism. Furthermore, CD47 cluster formation was dramatically inhibited on thbs1−/− mouse RBCs and associated with a significantly prolonged RBC lifespan. These results indicate that the strength of CD47 binding to its ligand TSP‐1 is predominantly determined by the distribution pattern and not the amount of CD47 molecules on RBCs, and offer direct evidence for the role of TSP‐1 in phagocytosis of aged RBCs. This study provides clear nanoscale pictures of aging‐associated changes in CD47 distribution and TSP‐1/CD47 interaction on the cell surface, and insights into the molecular basis for how these molecules coordinate to remove aged RBCs.
On young RBCs (Top), CD47 molecules reside as nanoclusters with minimal binding to TSP‐1 trimmers. On aged RBCs (Bottom), CD47 proteins form bigger and denser clusters and gain increased ability to bind TSP‐1, thus promoting phagocytosis of aged RBCs.
Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the ...progression of gastric cancer, among which m
A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan-Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m
A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m
A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.
Saving water is a common responsibility of all humanity, which is essential for achieving sustainable use of global water resources. The aim of this study is to discover the determinants of an ...individual's intention to save water. Based on the theory of planned behavior, a novel comprehensive framework has been developed by extending environmental concern, perceived risk, and information publicity. Partial least squares structural equation modeling was used to perform an empirical analysis with data from questionnaire of 265 residents in Jinan, the famous Chinese “Spring City”. The findings indicate that residents have a strong environmental concern and water-saving intention with mean values of 6.78 and 6.67, respectively. Attitude and information publicity are the most important antecedents of water-saving intention, followed by subjective norms and perceived behavioral control. Environmental concern and perceived risk indirectly affect the intention to save water through attitude, subjective norms, and perceived behavioral control. The role of environmental concern is more important than the role of perceived risk. Interestingly, a high level of information publicity may strengthen the impact of attitude on water-saving intention but weaken the impact of perceived behavioral control. This study strongly supplements current knowledge on water-saving behavior. Moreover, these findings provide insights for policymakers to motivate people to save water.
•A novel theoretical framework was constructed to explain water-saving intention.•The integrated model explains 81.8% of the variance in water-saving intention.•Attitude and information publicity encourage residents' water-saving intentions.•The role of environmental concern is more significant than the perceived risk.•The moderating effect of information publicity differs in different paths.
Background Because no large prospective studies are available, this study evaluated the clinical outcomes of two drug eluting stents in bifurcation lesions.
Methods Lesions with diameter of side ...branch ≥2.5 mm were selected. From October 2003 to June 2005, 112 patients with 113 bifurcation lesions were treated by two drug eluting stents （DESs）, technique. The location of bifurcation lesions were left anterior descending coronary artery/diagonal in 62 patients, left main distal bifurcation in 32, left circumflex coronary artery/obtute marginal branch in 18 and right coronary artery distal bifurcation in 1. Procedures for bifurcation lesions were crush or modified crush technique in 64, ＂T＂ stenting technique in 27, modified ＂Y＂ stenting, kiss stenting, ＂V＂ stenting as well as culotte stenting technique in 11, 5, 3 and 3, respectively. Among 226 lesions, 91 Cypher or Cypher select stents, 74 TAXUS and 67 Firebird were used. Final kiss balloon dilation was performed in 60 （93.7%） with crush technique after stenting.
Results Success rate of percutaneous coronary intervention for the bifurcation lesions was 100%. One patient, who developed inhospital acute myocardial infarction due to subacute thrombosis, was successfully treated by a second intervention. Major adverse cardiac events rate in-hospital was 0.89% （1/112） and during followup was 7.14% （8/112）, No death occurred during the followup of all patients. Angiographic followup was effected for 46 patients, restenosis for eight, coronary artery bypass grafting for 1 and a repeat intervention for 5. Restenosis involving TAXUS, Cypher and Firebird was 5 （5/18, 27.8%）, 2 （2/17, 11.8%） and 1 （1/11, 9.1%）, respectively （P〉0.05）. Total restenotic rate was 17.4% （8/46）.
Conclusions When ostium of side branch has severe stenosis and 〉12.5 mm in diameter, two-stent strategy in this bifurcation lesion is safe and effective, and the outcomes are satisfactory. Restenotic rates were not different between TAXUS, Cypher and Firebird DESs.
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•Schistosome infection could expand regulatory B cells (Bregs) in mice.•CD19±CD9± B cells produced more IL-10 than conventional B10 cells.•Adoptive transfer of CD9± B cells from ...infected mice had the capacity to markedly alleviate obesity-related inflammation.•CD9± B cells induced by helminth infection play a role in regulation of host metabolic disorders through IL-10 production.
It has been shown that helminth infection can protect against obesity and improve insulin sensitivity to a certain extent, based on epidemiological investigations and animal experiments. Meanwhile, helminths induce a network of regulatory immune cells, including regulatory B cells (Bregs). However, the molecule characteristics and function of these Bregs in improving whole-body metabolic homeostasis remains largely unclear. We established a mouse model with chronic Schistosoma japonicum infection, and compared the differences in B10 cells (CD19+CD5+CD1dhi) and B10− cells (CD19+CD5−CD1d−) from splenic B cells of infected mice using RNA-seq. A unique Breg population was identified. Furthermore, these Bregs were evaluated for their ability to produce inhibitory cytokines in vitro and suppress obesity when adoptively transferred into mice on a high-fat diet. We found that schistosome infection could expand Breg cell populations in mice. CD9 was demonstrated to be a key surface marker for most murine IL-10+ B cells in spleen. CD19+CD9+ B cells produced more IL-10 than conventional B10 cells. Adoptive transfer of CD9+ B cells had the capacity to alleviate obesity-associated inflammation via promoting Tregs, Th2 cells and decreasing Th1, Th17 cells in high-fat diet mice. In conclusion, schistosome infection can induce regulatory CD9+ B cell production, which plays a critical role in the regulation of metabolic disorders through IL-10 production.
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