ABSTRACT
Transcriptional regulation of inducible nitric oxide synthase (iNOS) is critically involved in the pathogenesis and progression of rheumatoid arthritis (RA); however, the specific ...transcription factors that control this process remain largely unidentified. In the present study, it was discovered that expression of the key erythroid factor, globin transcription factor 1 (GATA1), is significantly greater in human RA synovial tissues than in osteoarthritis (OA) tissues. IL 6 was found to induce synovial GATA1 expression in a signal transducer and activator of transcription 3‐dependent manner. Functionally, knockdown of GATA1 expression using specific small interfering RNA treatment was found to compromise immunoreaction‐elicited expression of proinflammatory cytokines and thus impair invasiveness of the human fibroblast‐like synovial cell line MH7A, whereas introduction of exogenous GATA1 was found to promote production of proinflammatory cytokines, leading to greater aggressiveness of MH7A cells. Mechanistically, GATA1 acts as the transcriptional coactivator of NOS2 (the gene encoding iNOS) transcription. Collectively, these data suggest that synovial GATA1 is an essential contributor to development and exacerbation of RA, presumably by inducing NOS2 transcription.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background:Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the ...regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson’s trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice.Conclusions:The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.
Absorbers with lightweight, low filler loading and broad absorption band are highly desirable for electromagnetic wave absorption field. Here, hollow Co1–xS microspheres constructed by nanosheets are ...fabricated via a facile synthetic method based on hydrothermal route. As an efficient wave absorber, the Co1–xS hollow spheres demonstrate excellent microwave absorption performance. With a weight content of only 3 wt%, the maximum reflection loss (RL) can reach as strong as −46.1 dB at 13.92 GHz and its qualified frequency bandwidth (with RL value over −10 dB) remarkably achieves 5.6 GHz, covering 35% of the entire measured bandwidth. In addition, compared with other cobalt sulfides (such as CoS2 and Co9S8), the Co1–xS microspheres with hollow structure exhibit more superior absorption intensity and broader qualified bandwidth. Therefore, this work provides a promising approach for the design and synthesis of hollow Co1–xS microspheres with lightweight and high‐performance microwave absorption.
The hollow Co1–xS microspheres with understanding microwave absorption performance are successfully fabricated through a facile hydrothermal route. The RLmax can reach to −46.1 dB at 13.92 GHz with an ultralow filler loading (3 wt%) and the effective frequency bandwidth is up to 5.6 GHz. Moreover, the possible wave absorption mechanism is also depicted comprehensively in this article.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Stimuli‐responsive DNA hydrogels are promising candidates for cancer treatment, as they not only possess biocompatible and biodegradable 3D network structures as highly efficient carriers for ...therapeutic agents but also are capable of undergoing programmable gel‐to‐solution transition upon external stimuli to achieve controlled delivery. Herein, a promising platform for highly efficient photothermal‐chemo synergistic cancer therapy is established by integrating DNA hydrogels with Ti3C2TX‐based MXene as a photothermal agent and doxorubicin (DOX) as a loaded chemotherapeutic agent. Upon the irradiation of near‐infrared light (NIR), temperature rise caused by photothermal MXene nanosheets triggers the reversible gel‐to‐solution transition of the DOX‐loaded MXene‐DNA hydrogel, during which the DNA duplex crosslinking structures unwind to release therapeutic agents for efficient localized cancer therapy. Removal of the NIR irradiation results in the re‐formation of DNA duplex structures and the hydrogel matrix, and the recombination of free DOX and adaptive hydrogel transformations can also be achieved. As demonstrated by both in vitro and in vivo models, the MXene‐DNA hydrogel system, with excellent biocompatibility and injectability, dynamically NIR‐triggered drug delivery, and enhanced drug uptake under mild hyperthermia conditions, exhibits efficient localized cancer treatment with fewer side effects to the organisms.
A photothermal‐chemo synergistic therapy system for localized cancer treatment is established by integrating responsive DNA hydrogel with MXene as the photothermal agent and doxorubicin as the chemotherapeutic agent. With excellent biocompatibility and biodegradability, good injectability, and highly efficient near‐infrared irradiation‐triggered drug delivery and uptake, the system exhibits efficient localized cancer treatment with less side effects to the organisms.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
LPL (lipoprotein lipase) is a rate-limiting enzyme involved in the hydrolysis of triglycerides. Previous studies have shown that microRNA (miR)-467b regulates hepatic LPL expression and plays a role ...in the progression of steatosis or abnormal lipid retention in obese mice. Macrophage-derived LPL has been shown to promote atherosclerosis. However, if miR-476b influences macrophage LPL expression and the subsequent effects are unknown. Here, we utilized oxLDL-treatment RAW 264.7 macrophages that were transfected with miR-467b mimics or inhibitors to investigate the potential roles of macrophage miR-476b. We found that miR-467b significantly decreased lipid accumulation and IL-6, IL-1β, TNF-α and MCP-1 secretions. Furthermore, our studies suggested an additional explanation for the regulatory mechanism of miR-467b on its functional target, LPL in RAW 264.7 macrophages. Thus, our findings indicate that miR-467b may regulate lipid accumulation and proinflammatory cytokine secretion in oxLDL-stimulated RAW 264.7 macrophages by targeting the LPL gene.
► MiR-467b reduces lipid accumulation and proinflammatory cytokine secretion in cell. ► MiR-467b specifically targets LPL by binding to its 3′UTR. ► LPL mediated lipid accumulation and proinflammatory cytokine secretion by miR-467b. ► MiR-467b may regulate the development of atherosclerosis by targeting LPL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence after chemotherapy and radiotherapy. Targeting BCSCs may ameliorate breast cancer ...relapse and therapy resistance. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) positively associates with breast cancer stemness and progression. Elevated TRIB3 expression supports BCSCs by interacting with AKT to interfere with the FOXO1-AKT interaction and suppress FOXO1 phosphorylation, ubiquitination, and degradation by E3 ligases SKP2 and NEDD4L. The accumulated FOXO1 promotes transcriptional expression of SOX2, a transcriptional factor for cancer stemness, which in turn, activates FOXO1 transcription and forms a positive regulatory loop. Disturbing the TRIB3-AKT interaction suppresses BCSCs by accelerating FOXO1 degradation and reducing SOX2 expression in mouse models of breast cancer. Our study provides insights into breast cancer development and confers a potential therapeutic strategy against TRIB3-overexpressed breast cancer.
In the arthropod gut, commensal microbiota maintain the immune deficiency (Imd)/Relish pathway for expression of antimicrobial peptides, whereas pathogenic bacteria induce dual oxidase 2 (Duox2) for ...production of extracellular microbicidal reactive oxygen species (ROS). The Imd/Relish pathway and the Duox2/ROS system are regarded as independent systems. Here, we report that these two systems are bridged by the tumor necrosis factor (TNF) ortholog PcEiger in the red swamp crayfish Procambarus clarkii. PcEiger expression is induced by commensal bacteria or the Imd/Relish pathway. PcEiger knockdown alters bacterial abundance and community composition due to variations in the oxidative status of the intestine. PcEiger induces Duox2 expression and ROS production by regulating the activity of the transcription factor Atf2. Moreover, PcEiger mediates regulation of the Duox2/ROS system by commensal bacteria and the Imd/Relish pathway. Our findings suggest that the Imd/Relish pathway regulates the Duox2/ROS system via PcEiger in P. clarkii, and they provide insights into the crosstalk between these two important mechanisms for arthropod intestinal immunity.
Synopsis
A new link between the Imd/Relish pathway and the Duox2/ROS system by PcEiger provides insights into the crosstalk between two critical intestinal immune mechanisms in the red swamp crayfish Procambarus clarkii.
The Imd/Relish pathway regulates the expression of PcEiger in the intestine of the red swamp crayfish regardless of the presence of pathogenic bacteria.
PcEiger stimulates intestinal Duox2 expression and ROS production.
PcEiger mediates regulation of the Duox2/ROS system by the Imd/Relish pathway.
A new link between the Imd/Relish pathway and the Duox2/ROS system by PcEiger provides insights into the crosstalk between two critical intestinal immune mechanisms in the red swamp crayfish Procambarus clarkii.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Understanding the dynamics and underlying mechanism of carbon exchange between terrestrial ecosystems and the atmosphere is one of the key issues in global change research. In this study, we ...quantified the carbon fluxes in different terrestrial ecosystems in China, and analyzed their spatial variation and environmental drivers based on the long‐term observation data of ChinaFLUX sites and the published data from other flux sites in China. The results indicate that gross ecosystem productivity (GEP), ecosystem respiration (ER), and net ecosystem productivity (NEP) of terrestrial ecosystems in China showed a significantly latitudinal pattern, declining linearly with the increase of latitude. However, GEP, ER, and NEP did not present a clear longitudinal pattern. The carbon sink functional areas of terrestrial ecosystems in China were mainly located in the subtropical and temperate forests, coastal wetlands in eastern China, the temperate meadow steppe in the northeast China, and the alpine meadow in eastern edge of Qinghai‐Tibetan Plateau. The forest ecosystems had stronger carbon sink than grassland ecosystems. The spatial patterns of GEP and ER in China were mainly determined by mean annual precipitation (MAP) and mean annual temperature (MAT), whereas the spatial variation in NEP was largely explained by MAT. The combined effects of MAT and MAP explained 79%, 62%, and 66% of the spatial variations in GEP, ER, and NEP, respectively. The GEP, ER, and NEP in different ecosystems in China exhibited ‘positive coupling correlation’ in their spatial patterns. Both ER and NEP were significantly correlated with GEP, with 68% of the per‐unit GEP contributed to ER and 29% to NEP. MAT and MAP affected the spatial patterns of ER and NEP mainly by their direct effects on the spatial pattern of GEP.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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