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Increasing evidence links metabolism, protein synthesis, and growth signaling to impairments in the function of hematopoietic stem and progenitor cells (HSPCs) during aging. The Lin28b/Hmga2 pathway controls tissue development, and the postnatal downregulation of this pathway limits the self-renewal of adult vs fetal hematopoietic stem cells (HSCs). Igf2bp2 is an RNA binding protein downstream of Lin28b/Hmga2, which regulates messenger RNA stability and translation. The role of Igf2bp2 in HSC aging is unknown. In this study, an analysis of wild-type and Igf2bp2 knockout mice showed that Igf2bp2 regulates oxidative metabolism in HSPCs and the expression of metabolism, protein synthesis, and stemness-related genes in HSCs of young mice. Interestingly, Igf2bp2 expression and function strongly declined in aging HSCs. In young mice, Igf2bp2 deletion mimicked aging-related changes in HSCs, including changes in Igf2bp2 target gene expression and impairment of colony formation and repopulation capacity. In aged mice, Igf2bp2 gene status had no effect on these parameters in HSCs. Unexpectedly, Igf2bp2-deficient mice exhibited an amelioration of the aging-associated increase in HSCs and myeloid-skewed differentiation. The results suggest that Igf2bp2 controls mitochondrial metabolism, protein synthesis, growth, and stemness of young HSCs, which is necessary for full HSC function during young adult age. However, Igf2bp2 gene function is lost during aging, and it appears to contribute to HSC aging in 2 ways: the aging-related loss of Igf2bp2 gene function impairs the growth and repopulation capacity of aging HSCs, and the activity of Igf2bp2 at a young age contributes to aging-associated HSC expansion and myeloid skewing.
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Envelhecimento , Células-Tronco Hematopoéticas , Proteínas de Ligação a RNA , Envelhecimento/genética , Animais , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Camundongos Knockout , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
INTRODUCTION: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies. METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL. RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels. CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.
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Fatores de Coagulação Sanguínea , Humanos , Tempo de Tromboplastina Parcial , Estudos Retrospectivos , Fatores de Coagulação Sanguínea/análise , Feminino , Masculino , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/diagnóstico , Curva ROC , Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/normas , Indicadores e ReagentesRESUMO
Chondrocyte senescence is a decisive component of age-related osteoarthritis, however, the function of small noncoding RNAs (sncRNAs) in chondrocyte senescence remains underexplored. Human hip joint cartilage chondrocytes were cultivated up to passage 4 to induce senescence. RNA samples were extracted and then analyzed using small RNA sequencing and qPCR. ß-galactosidase staining was used to detect the effect of sncRNA on chondrocyte aging. Results of small RNA sequencing showed that 279 miRNAs, 136 snoRNAs, 30 snRNAs, 102 piRNAs, and 5 rasiRNAs were differentially expressed in senescent chondrocytes. The differential expression of 150 sncRNAs was further validated by qPCR. Transfection of sncRNAs and ß-galactosidase staining were also performed to further revealed that hsa-miR-135b-5p, SNORA80B-201, and RNU5E-1-201 have the function to restrain chondrocyte senescence, while has-piR-019102 has the function to promote chondrocyte senescence. Our data suggest that sncRNAs have therapeutic potential as novel epigenetic targets in age-related osteoarthritis.
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MicroRNAs , Osteoartrite , Pequeno RNA não Traduzido , Humanos , Condrócitos/metabolismo , Osteoartrite/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Pequeno RNA não Traduzido/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismo , Epigênese Genética , Senescência CelularRESUMO
Eucommiae Cortex (EC) is frequently used alone or in combination with other active ingredients to treat a range of illnesses. An efficient technical instrument for changing cheap or plentiful organic chemicals into rare or costly counterparts is biotransformation. It combines EC with biotransformation techniques with the aim of producing some novel active ingredients, using different strains of bacteria that were introduced to biotransform EC in an aseptic environment. The high-quality strains were screened for identification after the fermentation broth was found using HPLC, and the primary unidentified chemicals were separated and purified in order to be structurally identified. Strain 1 was identified as Aspergillus niger and strain 2 as Actinomucor elegans; the main transformation product A was identified as pinoresinol (Pin) and B as dehydrodiconiferyl alcohol (DA). The biotransformation of EC utilizing Aspergillus niger and Actinomucor elegans is reported for the first time in this study's conclusion, resulting in the production of Pin and DA.
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Aspergillus niger , Biotransformação , Eucommiaceae , Fermentação , Lignanas , Mucor , Extratos Vegetais , Aspergillus niger/metabolismo , Mucor/metabolismo , Lignanas/química , Lignanas/metabolismo , Eucommiaceae/química , Extratos Vegetais/química , Furanos/metabolismo , Furanos/química , Cromatografia Líquida de Alta PressãoRESUMO
Highly efficient and reusable adsorbents for pesticide removal from wastewater have received increasing attention. In this study, Fe3O4 was synthesized using the solvothermal method. Fe3O4/xSiO2 and Fe3O4/xSiO2/ySiO2 were obtained through layer-by-layer silica (SiO2) coating on the surface of Fe3O4. SiO2 coating improved the dispersibility of the adsorbent, which can be separated from water rapidly under the action of the external magnetic field. The adsorption capacity of the adsorbent was investigated through removing pyraclostrobin from synthetic wastewater. The adsorbent showed the highest adsorption effect at the adsorbent concentration of 1 mg mL-1, at a pH of 7, and the adsorbent time of 110 min. The fitting model of the adsorption process conformed to the second-order kinetic model and the Langmuir model. The maximum adsorption capacity of Fe3O4/xSiO2/ySiO2 nanoparticles was 94.89 mg g-1, and the removal efficiency was about 96% at adsorption equilibrium. Acetone as the eluent can effectively desorb the adsorbent, and the desorbed adsorbent had high reusability. Particularly, the removal efficiency was still greater than 86% after 9 times of reuse. These results provide a reference for designing reusable nanoparticles to effectively absorb pesticides in wastewater.
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Hematopoietic stem cells (HSCs) undergo an age-related functional decline, which leads to a disruption of the blood system and contributes to the development of aging-associated hematopoietic diseases and malignancies. In this section, we provide a summary of the key hallmarks associated with HSC aging. We also examine the causal factors that contribute to HSC aging and emphasize potential approaches to mitigate HSC aging and age-related hematopoietic disorders.
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Doenças Hematológicas , Rejuvenescimento , Humanos , Envelhecimento , Células-Tronco Hematopoéticas/patologiaRESUMO
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus affecting human health globally. G-quadruplex secondary structures attract great attention as potential targets for antiviral strategy. In this study, we show that the CHIKV genome possesses several conserved potential G-quadruplex sequences. G-quadruplex ligands BRACO-19 and TMPyP4 could stabilize the CHIKV G-quadruplex and inhibit the transcription of constructs containing CHIKV G-quadruplex sequences. Importantly, BRACO-19 and TMPyP4 suppress CHIKV replication. Our study not only reinforces the presence of viral G-quadruplex sequences but also suggests that targeting G-quadruplex structure could represent a novel strategy to inhibit CHIKV.
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Febre de Chikungunya , Vírus Chikungunya , Animais , Antivirais/farmacologia , Vírus Chikungunya/genética , Humanos , Ligantes , Replicação ViralRESUMO
Antibiotics are broadly restricted in modern husbandry farming, necessitating the need for efficient and low-cost immunomodulatory preparations in antibiotic-free and healthful farming. As is known to all, CpG oligonucleotides (CpG-ODNs, an effective innate immunostimulatory agent) recognized by TLR9 in mammals (while TLR21 in avians) could collaborate with some united agent to induce stronger immune responses, but the cost is prohibitively expensive for farmers. Here, considering the coordination between TLR2 and TLR9/TLR21, we firstly proposed the idea that the well-fermented Lactococcus lactis could be utilized as a CpG-plasmid carrier (LACpG10) to enhance the host's innate immunity against pathogenic invasion. In the present study, after obtaining LACpG10-HL from homogenized and lyophilized recombinant strain LACpG10, we treated primary chicken lymphocytes, two cell lines (HD11 and IPEC-J2), and chickens with LACpG10-HL, CpG plasmids (pNZ8148-CpG10), and other stimulants, and respectively confirmed the effects by conducting qRT-PCR, bacterial infection assays, and a zoological experiment. Our data showed that LACpG10-HL could induce excellent innate immunity by regulating autophagy reactions, cytokine expression, and motivating PRRs. Interestingly, despite having no direct antiseptic effect, LACpG10-HL improved the antibacterial capacities of lymphocytes and enterocytes at the first line of defense. Most importantly, water-supplied LACpG10-HL treatment reduced the average adverse event rates, demonstrating that LACpG10-HL maintained its excellent immunostimulatory and protective properties under farming conditions. Our research not only contributes to revealing the satisfactory effects of LACpG10-HL but also sheds new light on a cost-effective solution with optimal immune effects in green, antibiotic-free, and healthful husbandry farming.
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Anti-Infecciosos Locais , Receptor Toll-Like 9 , Adjuvantes Imunológicos/farmacologia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos Locais/farmacologia , Galinhas/metabolismo , Citocinas/farmacologia , Imunidade Inata , Mamíferos/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Receptor 2 Toll-Like , Receptor Toll-Like 9/metabolismo , Água/farmacologiaRESUMO
The transformation of methane into high value-added chemicals such as aromatics provides a more desired approach towards sustainable chemistry but remains a critical challenge due to the low selectivity of aromatics and poor stability. Herein, we first report a coupling reaction of CH3 Cl and CO (CCTA) based on methane conversion, which achieves extremely high aromatics selectivity (82.2 %) with the selectivity of BTX up to ca. 60 % over HZSM-5. The promoting effects have been demonstrated on other zeolites especially 10-membered rings (10 MR) zeolites. Multiple characterizations show that 2,3-dimethyl-2-cyclopentene-1-one (DMCPO) is generated from acetyl groups and olefins. Furthermore, isotopic labeling analysis confirms that CO is inserted into the DMCPO and aromatics rings. A new aromatization mechanism is proposed, including the formation of the above intermediates, which conspicuously weakens the hydrogen transfer reaction, leading to a considerable increase of aromatics selectivity and a dramatic drop in alkanes.
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The selective conversion of methane to high value-added chemicals under mild conditions is of great significance for the commercially viable and sustainable utilization of methane but remains a formidable challenge. Herein, we report a strategy for efficiently converting methane to acetic acid via CH3 Cl as an intermediate. Up to 99.3 % acetic acid and methyl acetate (AA+MA) selectivity was achieved over pyridine-pretreated MOR (MOR-8) under moderate conditions of 523â K and 2.0â MPa. Water, conventionally detrimental to carbonylation reaction over zeolite catalysts, was conducive to the production of AA in the current reaction system. In the 100â h continuous test with the MOR-8 catalyst, the average AA+MA selectivity remained over 98 %. AA was formed by carbonylation of methoxy groups within 8-membered rings of MOR followed by hydrolysis. This strategy provided an approach for highly efficient utilization of methane to oxygenates under mild reaction conditions.
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Liver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Fibrose , Humanos , Hipóxia/complicações , Hipóxia/patologia , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Qualidade de VidaRESUMO
Nanoemulsions have become extremely popular water-insoluble pesticide delivery systems in recent years. In this study, prochloraz nanoemulsions were obtained by selecting the mixing ratio of surfactants (6:1, 3:1, 2:1, 1:1, 1:2, 1:3, and 1:6), surfactant concentration, and shearing time. The optimal formula was 10 wt % prochloraz, 6 wt % surfactant (2 wt % CO-100 + 4 wt % CO-360) dissolved in 6 wt % hydrocarbon solvent (S-100A), and deionized water replenished to 100 wt %. This formula meets the quality index standards of the Food and Agriculture Organization. Compared with oil-in-water emulsion (EW), the prochloraz nanoemulsion exhibited higher antifungal activity against Penicillium citrinum in vitro (lower LC50 of 1.17 mg L-1) and in vivo (fewer lesions). In addition, the L02 cells treated with the nanoemulsion had a higher survival rate and lower apoptosis rate at the same concentration. Results showed that the toxicity of the prochloraz nanoemulsion on L02 cells was lower than that of EW. The findings provide an important method for developing an efficient, safe, and environment-friendly nanoemulsion for postharvest fruit storage.
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Citrus sinensis , Penicillium , Emulsões , ImidazóisRESUMO
Misgurnus anguillicaudatus (M. anguillicaudatus) is a widely cultivated fish. However, in M. anguillicaudatus breeding, the frequent cold stress during daily breeding could induce immune suppression and increase the risk of infection, causing serious economic loss. Based on existing findings, CpG Oligonucleotides (CpG-ODNs) may be an ideal protective agent for low temperature fish breeding, performing anti-infective when faced with cold stress with cold shock proteins Y box binding proteins (YBX). Although YBX has pleiotropic functions, its roles in CpG-ODNs-mediated immunity (especially under cold situations) remain largely unexplored. To clarify the relationship among them, we identified the YBX1/YBX2 in M. anguillicaudatus and analyzed using a series of bioinformatics methods. After that, we immunized the fish with 3 types of CpG-ODNs and challenged with Aeromonas hydrophila (A. hydrophila). Here we showed that the best anti-bacterial effect of CpG-B was accompanied by the significant upregulation of YBX1. And the detection of the YBX1 downstream effectors confirmed that CpG-B induced the YBX1-mediated Th1 oriented responses to A. hydrophila by regulation of the NLRP3 (Caspase-A/-B), IL-1ß, IL-12 and IFN-γ. Afterwards, we found that under cold stress, CpG-B can activate the NLRP3 and NF-κB pathways through YBX1, a key mediator of anti-A. hydrophila in CpG-B immunization. In this study, we demonstrated CpG-B protection against infection in low temperature, and its interaction with YBX1, expanded the research of CpG-ODN under cold stress, and provided a new CpG-ODN application for low temperature fish farming.
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Infecções Bacterianas , Cipriniformes , Adjuvantes Imunológicos , Animais , Resposta ao Choque Frio , Proteína 3 que Contém Domínio de Pirina da Família NLR , OligodesoxirribonucleotídeosRESUMO
Clostridium butyricum (C. butyricum) is a probiotic that could promote animal growth and protect gut health. So far, current studies mainly keep up with the basic biological functions of C. butyricum, missing the effective strategy to further improve its protective efficiency. A recent report about C. butyricum alleviating intestinal injury through epidermal growth factor receptor (EGFR) inspired us to bridge this gap by porcine epidermal growth factor (EGF) overexpression. Lacking a secretory overexpression system, we constructed the recombinant strains overexpressing pEGF in C. butyricum for the first time and obtained 4 recombinant strains for highly efficient secretion of pEGF (BC/pPD1, BC/pSPP, BC/pGHF, and BC/pDBD). Compared to the wild-type strain, we confirmed that the expression level ranges of the intestinal development-related genes (Claudin-1, GLUT-2, SUC, GLP2R, and EGFR) and anti-inflammation-related gene (IL-10) in IPECs were upregulated under recombinant strain stimulation, and the growth of Staphylococcus aureus and Salmonella typhimurium was significantly inhibited as well. Furthermore, a particular inhibitor (stattic) was used to block STAT3 tyrosine phosphorylation, resulting in the downregulation on antibacterial effect of recombinant strains. This study demonstrated that the secretory overexpression of pEGF in C. butyricum could upregulate the expression level of EGFR, consequently improving the intestinal protective functions of C. butyricum partly following STAT3 signal activation in IPECs and making it a positive loop. These findings on the overexpression strains pointed out a new direction for further development and utilization of C. butyricum. KEY POINTS: ⢠By 12 signal peptide screening in silico, 4 pEGF overexpression strains of C. butyricum/pMTL82151-pEGF for highly efficient secretion of pEGF were generated for the first time. ⢠The secretory overexpression of pEGF promoted the intestinal development, antimicrobial action, and anti-inflammatory function of C. butyricum. ⢠The overexpressed pEGF upregulated the expression level of EGFR and further magnified the gut protective function of recombinant strains which in turn partly depended on STAT3 signal pathway in IPECs.
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Clostridium butyricum , Probióticos , Animais , Fator de Crescimento Epidérmico , Sinais Direcionadores de Proteínas , Transdução de Sinais , SuínosRESUMO
Compared with conventional lasers, the random laser is realized through strong multiple scatterings in disordered gain system. In this paper, random lasing (RL) in one-dimensional metal surface plasmon (SP) waveguide with gold-plated self-formed silicon pyramids was investigated comprehensively. Consequently, the emission intensity of RL was enhanced dramatically and the RL threshold was reduced significantly through Au-coated Si spiky tips. Meanwhile, one-dimensional metal SP channel waveguides confined the emitting light in a certain direction with a small divergence angle. Using FDTD simulations, it was found that the enhancement effect for RL is likely attributed to the localized surface plasmon (LSP) field. In addition, the LSP field nearby the spiky tips can enhance field-molecule interaction, which was benefit for lasing in small scale. The results in this letter supplied a feasible method to realize the application of RL in subwavelength optical elements.
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Proteus hauseri ZMd44, a biodecolorizing bacterium, has been known to produce electricity and multicopper oxidase (Mco-laccase) under copper induction. However, optimization and regulation of production have not been explored. This study is the first attempt to evaluate several parameters on biomass and Mco-laccase production of P. hauseri ZMd44. Through orthogonal experiments with Taguchi's L9, it was found that P. hauseri ZMd44 was sensitive to pH value. The cells grew relatively quickly at pH 7, thus the biomass and Mco-laccase production reached 1.66 g/L and 1043.6 U/L, respectively. Higher pH values also influenced the swarming motility, which is an important characteristic of P. hauseri ZMd44 that affects urinary tract infection. The swarming circle and the diameter of the swarm, represented by the motility velocity, were found to be more controlled after 24 h of growth at pH 6. The swarming ability of P. hauseri was completely inhibited by the addition of 3 mM copper or zinc ions. Therefore, the Mco-laccase and swarming motility could be controlled by regulating pH and ion content.
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Proteínas de Bactérias/metabolismo , Cobre/metabolismo , Lacase/metabolismo , Proteus/citologia , Proteus/metabolismo , Proliferação de Células , Eletricidade , Humanos , Concentração de Íons de Hidrogênio , Infecções por Proteus/microbiologia , Zinco/metabolismoRESUMO
The conversion of methanol into aromatics over unmodified H-ZSM-5 zeolite is generally not high because the hydrogen transfer reaction results in alkane formation. Now circa 80 % aromatics selectivity for the coupling reaction of methanol and carbon monoxide over H-ZSM-5 is reported. Carbonyl compounds and methyl-2-cyclopenten-1-ones (MCPOs), which were detected in the products and catalysts, respectively, are considered as intermediates. The latter species can be synthesized from the former species and olefins. 13 C isotope tracing and 13 C liquid-state NMR results confirmed that the carbon atoms of CO molecules were incorporated into MCPOs and aromatic rings. A new aromatization mechanism that involves the formation of the above intermediates and co-occurs with a dramatically decreased hydrogen transfer reaction is proposed. A portion of the carbons in CO molecules are incorporated into aromatic, which is of great significance for industrial applications.
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Wild-type p53-induced phosphatase 1 (Wip1), a phosphatase previously considered as an oncogene, has been implicated in the regulation of thymus homeostasis and neutrophil maturation. However, the role of Wip1 in B-cell development is unknown. We show that Wip1-deficient mice exhibit a significant reduction of B-cell numbers in the bone marrow, peripheral blood, and spleen. A reciprocal transplantation approach revealed a cell-intrinsic defect in early B-cell precursors caused by Wip1 deficiency. Further experiments revealed that Wip1 deficiency led to a sustained activation of p53 in B cells, which led to increased level of apoptosis in the pre-B-cell compartment. Notably, the impairment of B-cell development in Wip1-deficient mice was completely rescued by genetic ablation of p53, but not p21. Therefore, loss of Wip1 phosphatase induces a p53-dependent, but p21-independent, mechanism that impairs B-cell development by enhancing apoptosis in early B-cell precursors. Moreover, Wip1 deficiency exacerbated a decline in B-cell development caused by aging as evidenced in mice with aging and mouse models with serial competitive bone marrow transplantation, respectively. Our present data indicate that Wip1 plays a critical role in maintaining antigen-independent B-cell development in the bone marrow and preventing an aging-related decline in B-cell development.
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Linfócitos B/citologia , Linfócitos B/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Envelhecimento/imunologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Apoptose , Linfócitos B/imunologia , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Diferenciação Celular , Inibidor de Quinase Dependente de Ciclina p21/deficiência , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Feminino , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfoproteínas Fosfatases/deficiência , Fosfoproteínas Fosfatases/genética , Células Precursoras de Linfócitos B/citologia , Células Precursoras de Linfócitos B/imunologia , Células Precursoras de Linfócitos B/metabolismo , Proteína Fosfatase 2C , Transdução de SinaisRESUMO
BACKGROUND AND OBJECTIVE: The mammalian target of rapamycin (mTOR) signalling pathway regulates immune responses, and promotes cell growth and differentiation. Inhibition of mTOR with rapamycin modulates allergic asthma, while the underlying molecular mechanisms remain elusive. Here, we demonstrate that rapamycin, effectively inhibits eosinophil differentiation, contributing to its overall protective role in allergic airway inflammation. METHODS: Rapamycin was administered in a mouse model of ovalbumin-induced allergic airway inflammation, and the eosinophil differentiation was analysed in vivo and in vitro. RESULTS: Rapamycin significantly attenuated allergic airway inflammation and markedly decreased the amount of eosinophils in local airways, peripheral blood and bone marrow, independently of levels of interleukin-5 (IL-5). In vitro colony forming unit assay and liquid culture demonstrated that rapamycin directly inhibited IL-5-induced eosinophil differentiation. In addition, rapamycin reduced the production of IL-6 and IL-13 by eosinophils. Rapamycin was also capable of reducing the eosinophil levels in IL-5 transgenic NJ.1638 mice, again regardless of the constitutive high levels of IL-5. Interestingly, rapamycin inhibition of eosinophil differentiation in turn resulted in an accumulation of eosinophil lineage-committed progenitors in bone marrow. CONCLUSIONS: Altogether these results clearly demonstrate a direct inhibitory role of rapamycin in eosinophil differentiation and function, and reemphasize the importance of rapamycin and possibly, mTOR, in allergic airway disease.
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Asma , Diferenciação Celular , Eosinófilos , Inflamação , Sirolimo/farmacologia , Animais , Asma/tratamento farmacológico , Asma/imunologia , Asma/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Hipersensibilidade/imunologia , Imunossupressores/farmacologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Interleucinas/imunologia , Contagem de Leucócitos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Ovalbumina/farmacologia , Inibidores de Serina Proteinase/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/imunologiaRESUMO
The food industry holds immense promise for 3D printing technology. Current research focuses mainly on optimizing food material composition, molding characteristics, and printing parameters. However, there is a notable lack of comprehensive studies on the shape changes of food products, especially in modeling and simulating deformations. This study addresses this gap by conducting a detailed simulation of the starch gel printing and deformation process using COMSOL Multiphysics 6.2 software. Additive manufacturing (AM) technology is widely acclaimed for its user-friendly operation and cost-effectiveness. The 3D printing process may lead to changes in part dimensions and mechanical properties, attributable to the accumulation of residual stresses. Studies require a significant amount of time and effort to discover the optimal composition of the printed material and the most effective deformed 3D structure. There is a risk of failure, which can lead to wasted resources and research delays. To tackle this issue, this study thoroughly analyzes the physical properties of the gel material through COMSOL Multiphysics 6.2 software, It simulates the heat distribution during the 3D printing process, providing important insights into how materials melt and solidify. Three-part models with varying aspect ratios were meticulously designed to explore shape changes during both the printing process and exposure to an 80 °C environment, employing NMR and rheological characterization. Using the generalized Maxwell model for material simulation in COMSOL Multiphysics, the study predicted stress and deformation of the parts by analyzing solid heat transfer and solid mechanics physical fields. Simulation results showed that among three models utilizing a gel-PET plastic membrane bilayer structure, Model No. 1, with the largest aspect ratio, exhibited the most favorable deformation under an 80 °C baking environment. It displayed uniform bending in the transverse direction without significant excess warpage in the edge direction. In contrast, Models No. 2 and No. 3 showed varying degrees of excess warpage at the edges, with Model No. 3 exhibiting a more pronounced warpage. These findings closely aligned with the actual printing outcomes.