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Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.
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The stoichiometric characteristics of leaves can reflect environmental adaptation of plants, and thus the study of the relationship between them is helpful for exploring plant adaptation strategies. In this study, taking the national second-level key protection species, Ammopiptanthus mongolicus, as the research object, we set up 26 plots to collect samples, and measured the content of carbon (C), nitrogen (N), phosphorus (P) and water use efficiency (WUE) of leaves. We analyzed the relationship between leaf stoichiometric characteristics and WUE, and quantified the contributions of soil, climate, and water use efficiency to the variations of leaf stoichiometry. The results showed that C, N, and P contents in the leaves were (583.99±27.93), (24.31±2.09), and (1.83±0.06) mg·g-1, respectively. The coefficients of variation were 4.8%, 8.6%, and 3.2%, respectively, all belonging to weak variability, indicating that foliar contents of C, N and P tended to a certain stable value. The average value of N:P was 13.3, indicating that the growth of A. mongolicus was mainly limited by N. WUE was not correlated with leaf C content, but was significantly positively correlated with leaf N and P contents and N:P, and significantly negatively correlated with C:N and C:P, indicating that there was a linear synergistic trend between WUE and leaf nutrient content. The main factors influencing leaf C content and C:P were climatic factors, the leaf N content and N:P were mainly affected by soil factors, and the water use efficiency mainly affected leaf P content and C:N, indicating that the driving factors of different stoichiometric characteristics were different. The results could help eva-luate the habitat adaptation of desert plants, which would provide a theoretical basis for the conservation and management of A. mongolicus.
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Carbono , Nitrogênio , Fósforo , Folhas de Planta , Folhas de Planta/química , Folhas de Planta/metabolismo , Folhas de Planta/crescimento & desenvolvimento , China , Nitrogênio/análise , Nitrogênio/metabolismo , Fósforo/análise , Fósforo/metabolismo , Carbono/análise , Carbono/metabolismo , Ecossistema , Água/análise , Água/metabolismo , Água/química , Adaptação Fisiológica , Solo/químicaRESUMO
Atrazine (ATR) is a widely used herbicide worldwide that can cause kidney damage in humans and animals by accumulation in water and soil. Lycopene (LYC), a carotenoid with numerous biological activities, plays an important role in kidney protection due to its potent antioxidant and anti-inflammatory effects. The current study sought to investigate the role of interactions between mtDNA and the cGAS-STING signaling pathway in LYC mitigating PANoptosis and inflammation in kidneys induced by ATR exposure. In our research, 350 mice were orally administered LYC (5 mg/kg BW/day) and ATR (50 or 200 mg/kg BW/day) for 21 days. Our results reveal that ATR exposure induces a decrease in mtDNA stability, resulting in the release of mtDNA into the cytoplasm through the mPTP pore and the BAX pore and the mobilization of the cGAS-STING pathway, thereby inducing renal PANoptosis and inflammation. LYC can inhibit the above changes caused by ATR. In conclusion, LYC inhibited ATR exposure-induced histopathological changes, renal PANoptosis, and inflammation by inhibiting the cGAS-STING pathway. Our results demonstrate the positive role of LYC in ATR-induced renal injury and provide a new therapeutic target for treating renal diseases in the clinic.
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Atrazina , DNA Mitocondrial , Rim , Licopeno , Proteínas de Membrana , Substâncias Protetoras , Animais , Camundongos , Atrazina/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Licopeno/farmacologia , Licopeno/administração & dosagem , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Masculino , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Humanos , Herbicidas , Nefropatias/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Nefropatias/genética , Nefropatias/tratamento farmacológico , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Background: Complications frequently occur after neonatal enterostomy. Enterostomy formation is a common outcome following an emergency neonatal laparotomy. This study investigated whether the incidence of complications after enterostomy could be decreased with a drainage device (composed of foreskin cerclage staple, a condom, and a 0-Mersilk braided nonabsorbable suture) fixed in the proximal ostomy bowel tube to improve proximal enterostomy in newborns. Methods: This study was a retrospective case note review of the incidence of emergency neonatal enterostomy incidence over a 3-year period (2/2016-2/2019) at the authors' center. A single surgeon conducted all surgeries. The incidence of intraoperative and postoperative complications was compared between modified and traditional surgery groups. Results: All 47 surgeries were successfully completed (32 boys and 15 girls; sex ratio: 2.13:1). The mean (±SD) birth weight, gestational period, and daily age were 2.64 ± 0.81 kg 35.62 ± 3.76 weeks and 3.49 ± 5.61 days, respectively. The patients were divided into modified surgery groups (20 cases) and traditional surgery groups (27 cases). The modified surgery group had significantly lower rates of total complications, unplanned reoperations, wound-related complications, and stoma-related complications than the traditional group (p <0.05). Conclusions: The preliminary observations suggested that the simple drainage device was a safe and effective operation device that reduced the risk of stoma-related complications.
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The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.
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Atrazine (ATR) is widely used worldwide as a commercial herbicide, Diaminochlorotriazine (DACT) is the main metabolite of ATR in the organism. Both of them disrupt the production of steroids and induce abnormal reproductive development. The granulosa cells (GCs) are important for growth and reproduction of animals. However, the toxicity of ATR on the GCs of birds is not well clarified. To evaluate the effect of the environmental pollutant ATR on bird GCs. The quail GCs were allotted into 7 groups, C (The medium of M199), A20 (20 µM ATR), A100 (100 µM ATR), A250 (250 µM ATR), D20 (20 µM DACT), D100 (100 µM DACT) and D200 (200 µM DACT). The results demonstrated that ATR reduced the viability of GCs, disrupted mitochondrial structure (including mitochondrial cristae fragmentation and the mitochondrial morphology disappearance) and decreased mitochondrial membrane potential. Meanwhile, ATR interfered with the expression of key factors in the steroid synthesis pathway, inducing the secretion of the sex hormones E2 and P in GCs. which in turn induced apoptosis. Furthermore, the Nrf2/ARE pathway as a potential target to ameliorate ATR-induced endocrine disruption in GCs for proper reproductive functions. Our research provides a new perspective for understanding the effects of ATR on reproductive functions in birds.
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Atrazina , Disruptores Endócrinos , Células da Granulosa , Herbicidas , Fator 2 Relacionado a NF-E2 , Animais , Atrazina/toxicidade , Células da Granulosa/efeitos dos fármacos , Feminino , Herbicidas/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Disruptores Endócrinos/toxicidade , Coturnix , Proteínas Aviárias/metabolismo , Proteínas Aviárias/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
Noise-enhanced applications in open quantum walk (QW) has recently seen a surge due to their ability to improve performance. However, verifying the success of open QW is challenging, as mixed-state tomography is a resource-intensive process, and implementing all required measurements is almost impossible due to various physical constraints. To address this challenge, we present a neural-network-based method for reconstructing mixed states with a high fidelity (â¼97.5%) while costing only 50% of the number of measurements typically required for open discrete-time QW in one dimension. Our method uses a neural density operator that models the system and environment, followed by a generalized natural gradient descent procedure that significantly speeds up the training process. Moreover, we introduce a compact interferometric measurement device, improving the scalability of our photonic QW setup that enables experimental learning of mixed states. Our results demonstrate that highly expressive neural networks can serve as powerful alternatives to traditional state tomography.
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Cadmium (Cd) is a well-known testis toxicant. The blood-testis barrier (BTB) is a crucial component of the testis. Cd can disrupt the integrity of the BTB and reproductive function. However, the mechanism of Cd-induced disruption of BTB and testicular damage has not been fully elucidated. Here, our study investigates the effects of Cd on BTB integrity and testicular dysfunction. 80 (aged 1 day) Hy-Line white variety chickens were randomly designed into 4 groups and treated for 90 days, as follows: control group (essential diet), 35 Cd, 70 Cd and 140 Cd groups (35, 70 and 140 mg/kg Cd). The results found that Cd exposure diminished volume of the testes and induced histopathological lesions in the testes. Exposure to Cd induced an inflammatory response, disrupted the structure and function of the FAK/occludin/ZO-1 protein complex and disrupted the tight junction and adherens junction in the BTB. In addition, Cd exposure reduced the expression of steroid-related proteins and inhibited testosterone synthesis. Taken together, these data elucidate that Cd disrupts the integrity of the BTB and further inhibits spermatogenesis by dissociating the FAK/occludin/ZO-1 complex, which provides a basis for further investigation into the mechanisms of Cd-induced impairment of male reproductive function and pharmacological protection.
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Barreira Hematotesticular , Cádmio , Galinhas , Testículo , Animais , Masculino , Barreira Hematotesticular/efeitos dos fármacos , Cádmio/toxicidade , Quinase 1 de Adesão Focal/metabolismo , Ocludina/metabolismo , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.
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Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , NF-kappa B/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/farmacologia , Receptor 4 Toll-Like/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Aterosclerose/genética , Placa Aterosclerótica/metabolismo , Transdução de Sinais , Macrófagos/metabolismo , LipídeosRESUMO
In this paper, a dual interface trapezium liquid prism with beam steering function is implemented and analyzed. The electrowetting-on-dielectric method is used to perform the desired beam steering function without mechanical moving parts. This work examines deflection angles at different applied voltages to determine the beam steering range. The deflection angle can be experimentally measured from 0° to 3.43°. The proposed liquid prism can be applied in the field of optical manipulation, solar collecting system and so on.
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BACKGROUND: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. METHODS: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-ß were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. RESULTS: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1-/- rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-ß, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic ß cells. CONCLUSIONS: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.
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The cocoon silk of silkworms (Bombyx mori) has multiple potential applications in biomedicine due to its good biocompatibility, mechanical properties, degradability, and plasticity. Numerous studies have confirmed that silk material dressings are more effective than traditional ones in the skin wound healing process. Silk material research has recently moved toward functionalized biomaterials and achieved remarkable results. Herein, we summarize the recent advances in functionalized silk materials and their efficacy in skin wound healing. In particular, transgenic technology has realized the specific expression of human growth factors in the silk glands of the silkworms, which lays the foundation for fabricating novel and low-cost functionalized materials. Without a green and safe preparation process, the best raw silk materials cannot be made into medically safe products. Therefore, we provide an overview of green and gentle approaches for silk degumming and silk sericin (SS) extraction. Moreover, we summarize and discuss the processing methods of silk fibroin (SF) and SS materials and their potential applications, such as burns, diabetic wounds, and other wounds. This review aims to enhance our understanding of new advances and directions in silk materials and guide future biomedical research.
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Bombyx , Fibroínas , Animais , Humanos , Seda , Materiais Biocompatíveis/farmacologia , Cicatrização , Fibroínas/farmacologiaRESUMO
The granulosa cells (GCs) of birds are essential for the reproduction and maintenance of populations in nature. Atrazine (ATR) is a potent endocrine disruptor that can interfere with reproductive function in females and Diaminochlorotriazine (DACT) is the primary metabolite of ATR in the organism. Melatonin (MT) is an endogenous hormone with antioxidant properties that plays a crucial role in development of animal germ cells. However, how ATR causes mitochondrial dysfunction, abnormal secretion of steroid hormones, and whether MT prevents ATR-induced female reproductive toxicity remains unclear. Thus, the purpose of this study is to investigate the protective effect of MT against ATR-induced female reproduction. In the present study, the GCs of quail were divided into 6 groups, as follows: C (Serum-free medium), MT (10 µM MT), A250 (250 µM ATR), MA250 (10 µM MT+250 µM ATR), D200 (200 µM DACT) and MD200 (10 µM MT+200 µM DACT), and were cultured for 24 h. The results revealed that ATR prevented GCs proliferation and decreased cell differentiation. ATR caused oxidative damage and mitochondrial dysfunction, leading to disruption of steroid synthesis, which posed a severe risk to GC's function. However, MT supplements reversed these changes. Mechanistically, our study exhibited that the ROS/SIRT1/STAR axis as a target for MT to ameliorate ATR-induced mitochondrial dysfunction and steroid disorders in GCs, which provides new insights into the role of MT in ATR-induced reproductive capacity and species conservation in birds.
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Atrazina , Herbicidas , Melatonina , Doenças Mitocondriais , Animais , Feminino , Atrazina/toxicidade , Atrazina/metabolismo , Células da Granulosa/metabolismo , Herbicidas/toxicidade , Herbicidas/metabolismo , Melatonina/farmacologia , Doenças Mitocondriais/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/efeitos dos fármacos , Sirtuína 1/metabolismo , Esteroides/metabolismo , Codorniz/genética , Codorniz/metabolismoRESUMO
Recycling resources from wastewater is even more important for developing a more sustainable society. Disposing sewage sludge, which accumulates most pollutants and resources in sewage, is the main challenge in wastewater pollution control and resource utilization. Heavy metals (HMs) are the greatest constraint limiting the application of sewage sludge to land as a sustainable use of this material. We conducted a meta-analysis of the concentrations of HMs in Chinese sewage sludge by combining data from studies published from 2000 to 2019 (N = 8477). Over this period, the reported concentrations of HMs in sewage sludge declined in three stages (a fluctuating stage, a slight decrease stage, and a rapid and stable decrease stage). The results revealed that economic development and environmental policy implementation were the main factors mitigating HM pollution in sewage sludge in China. Moreover, if environmental regulations were strengthened and HM pollution-mitigation strategies were made consistent, such that the proportion of sewage sludge applied to land in China could be increased from 18.6% to 48.0% (the proportion applied to land in the United States), the ecosystem services analysis showed that huge ecological-economic benefits could be realized (3.1 billion Chinese Yuan) and the use of fertilizers could be substantially reduced (the use of nitrogen fertilizers by 8.5% and the use of phosphate fertilizers by 18.1%). This review shows that China should formulate a unified policy and interdepartmental committee for sustainable application of sewage sludge to land and wastewater resource recycling management.
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Metais Pesados , Esgotos , Esgotos/análise , Águas Residuárias , Ecossistema , Fertilizantes/análise , Estudos de Viabilidade , Nutrientes/análise , Metais Pesados/análise , ChinaRESUMO
Soybean is one of the most widely grown oilseed crops worldwide. Several unfavorable factors, including salt and salt-alkali stress caused by soil salinization, affect soybean yield and quality. Therefore, exploring the molecular basis of salt tolerance in plants and developing genetic resources for genetic breeding is important. Sucrose non-fermentable protein kinase 1 (SnRK1) belongs to a class of Ser/Thr protein kinases that are evolutionarily highly conserved direct homologs of yeast SNF1 and animal AMPKs and are involved in various abiotic stresses in plants. The GmPKS4 gene was experimentally shown to be involved with salinity tolerance. First, using the yeast two-hybrid technique and bimolecular fluorescence complementation (BiFC) technique, the GmSNF1 protein was shown to interact with the GmPKS4 protein. Second, the GmSNF1 gene responded positively to salt and salt-alkali stress according to qRT-PCR analysis, and the GmSNF1 protein was localized in the nucleus and cytoplasm using subcellular localization assay. The GmSNF1 gene was then heterologously expressed in yeast, and the GmSNF1 gene was tentatively identified as having salt and salt-alkali tolerance function. Finally, the salt-alkali tolerance function of the GmSNF1 gene was demonstrated by transgenic Arabidopsis thaliana, soybean hairy root complex plants overexpressing GmSNF1 and GmSNF1 gene-silenced soybean using VIGS. These results indicated that GmSNF1 might be useful in genetic engineering to improve plant salt and salt-alkali tolerance.
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Proteínas de Arabidopsis , Arabidopsis , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Soja/genética , Glycine max/metabolismo , Álcalis/metabolismo , Saccharomyces cerevisiae/metabolismo , Melhoramento Vegetal , Estresse Fisiológico/genética , Arabidopsis/metabolismo , Proteínas Quinases/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Arabidopsis/genéticaRESUMO
Eosinophilic gastritis is characterized by gastrointestinal symptoms accompanied by peripheral eosinophilia. This study aims to explore the association between eosinophilic gastritis and Synaptosome Associated Protein 25 (SNAP25), and provide a new direction for the diagnosis and treatment of eosinophilic gastritis. GSE54043 was downloaded from the gene expression omnibus database. Differentially expressed genes (DEGs) were screened. The functions of common DEGs were annotated by Database for Annotation, Visualization and Integrated Discovery and Metascape. The protein-protein interaction network of common DEGs was obtained by Search Tool for the Retrieval of Interacting Genes and visualized by Cytoscape. Significant modules were identified from the protein-protein interaction network. A total of 186 patients with eosinophilic gastritis were recruited. The clinical data were recorded and the expression levels of CPE, SST, PCSK2, SNAP25, and SYT4 were detected. Pearson chi-square test and Spearman correlation coefficient were used to analyze the relationship between eosinophilic gastritis and related parameters. Univariate and multivariate Logistic regression were used for further analysis. 353 DEGs were presented. The top 10 genes screened by cytoHubb were shown, and Veen diagram figured out 5 mutual genes. Pearson's chi-square test showed that SNAP25 (P < .001) was significantly associated with eosinophilic gastritis. Spearman correlation coefficient showed a significant correlation between eosinophilic gastritis and SNAP25 (ρ = -0.569, P < .001). Univariate logistic regression analysis showed that SNAP25 (OR = 0.046, 95% CI: 0.018-0.116, P < .001) was significantly associated with eosinophilic gastritis. Multivariate logistic regression analysis showed that SNAP25 (OR = 0.024, 95% CI: 0.007-0.075, P < .001) was significantly associated with eosinophilic gastritis. The low expression of SNAP25 gene in eosinophilic gastritis is associated with a higher risk of eosinophilic gastritis.
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Enterite , Eosinofilia , Humanos , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas , Eosinofilia/genética , Proteína 25 Associada a Sinaptossoma/genéticaRESUMO
Recognition of intracellular nucleic acids is a vital step for host to mount prompt immune responses against microbial pathogens. However, inappropriate response to self-nucleic acids leads to sustained type I interferon (IFN) production, which is implicated in the development of several autoimmune diseases, such as Aicardi-Goutières syndrome (AGS). Therefore, effective confinement of intracellular nucleic acid-induced IFN expression is a potential strategy for the treatment of such autoimmune diseases. In this study, we found that rosmarinic acid (RA), a natural compound isolated from rosemary, inhibits intracellular nucleic acid-stimulated IFN expression. Mechanistic investigation revealed that RA binds to both G3BP1 and cGAS, and impairs cGAS activation through disrupting the binding of DNA with cGAS. More importantly, we showed that RA could effectively attenuate the expression of IFN-stimulated genes (ISGs) in the well-established cell models for AGS. Thus, our study provides a promising compound for the treatment of autoimmune responses induced by aberrant nucleic acid-sensing.
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Doenças Autoimunes , Interferon Tipo I , Ácidos Nucleicos , Humanos , Interferon Tipo I/metabolismo , Autoimunidade , DNA Helicases/metabolismo , RNA Helicases/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas com Motivo de Reconhecimento de RNA , Doenças Autoimunes/genética , Nucleotidiltransferases/metabolismo , Ácido RosmarínicoRESUMO
The inhibition of tyrosinase is considered to be a common therapeutic strategy for some hyperpigmentation disorders. Screening of tyrosinase inhibitors is of great significance to the treatment of pigmentation diseases. In this study, tyrosinase was covalently immobilized on magnetic multi-walled carbon nanotubes for the first time, and the immobilized tyrosinase was applied for ligand fishing of tyrosinase inhibitors from complex medicinal plants. The immobilized tyrosinase was characterized by transmission electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, vibrating sample magnetometry, and thermo-gravimetric analyzer, which indicated that tyrosinase was immobilized onto magnetic multi-walled carbon nanotubes. The immobilized tyrosinase showed better thermal stability and reusability than the free one. The ligand was fished out from Radix Paeoniae Alba and identified as 1,2,3,4,6-pentagalloylglucose by ultra-performance liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. 1,2,3,4,6-pentagalloylglucose was found to be a tyrosinase inhibitor with similar half maximal inhibitory concentration values of 57.13 ± 0.91 µM compared to kojic acid (41.96 ± 0.78 µM). This work not only established a new method for screening tyrosinase inhibitors but also holds considerable potential for exploring the new medicinal value of medicinal plants.
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Monofenol Mono-Oxigenase , Nanotubos de Carbono , Monofenol Mono-Oxigenase/química , Nanotubos de Carbono/química , Ligantes , Fenômenos Magnéticos , Enzimas Imobilizadas/químicaRESUMO
To explore the stoichiometric characteristics of C, N and P and adaptive mechanism of mosses in mountain forest ecosystems, we set up 15 plots along the altitude gradient in Picea crassifolia forest in Helan Mountains, Ningxia. We analyzed the C:N:P stoichiometry of moss aboveground tissues and its relationship with environmental factors. The results showed the mean values of C, N and P concentration in moss aboveground tissues were 336.67, 20.31 and 0.66 mg·g-1, respectively. The mean value of aboveground tissue N:P was 33.4, indicating that the growth of mosses was limited by P. The C concentration in the aboveground tissues of mosses was positively correlated with soil total nitrogen concentration and negatively correlated with soil total phosphorus concentration. The N concentration in aboveground tissues of mosses was significantly negatively correlated with soil organic carbon and soil total nitrogen concentrations. Results of redundancy analysis showed that the interpretation rate of environmental factors on the stoichiometry was 48.5%, with canopy closure, soil total nitrogen and soil total phosphorus as the main factors. Canopy closure was the main environmental factor affecting the growth of mosses in P. crassifolia forest in Helan Mountains. High canopy closure facilitated the growth of mosses.
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Briófitas , Picea , Ecossistema , Carbono/análise , Solo , Florestas , China , Nitrogênio/análise , Fósforo/análiseRESUMO
BACKGROUND: Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for cytosolic DNA-sensing and the subsequent immune responses. The inappropriate activation of this pathway leads to DNA-induced autoimmune response. Understanding the precise regulation of cGAS-STING pathway is important for developing therapeutics to treat several autoimmune diseases caused by self-DNA. RESULTS: We report that Meloxicam (MXC) inhibits intracellular DNA-, but not RNA-induced immune responses. We find that MXC inhibits the phosphorylation of STING by examining in different cells with various DNA stimulations. We further find that MXC significantly dampens the expression levels of interferon-stimulated genes (ISGs) by using DNA 3' repair exonuclease 1 (TREX1)-deficient cell, an experimental model for self-DNA-induced autoimmune disease. Importantly, we demonstrate that MXC could promote the survival in Trex1-/- mouse model for Aicardi-Goutières syndrome (AGS). CONCLUSIONS: Our study identified a non-steroidal anti-inflammatory drug, MXC, that exhibits potential effect in treating the autoimmunity caused by self-DNA.