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Oil-contaminated wastewater has been one of the most concerned environmental issues. Superwetting materials-enabled remediation of oil contamination in wastewater faces the critical challenge of fouling problems due to the formation of intercepted phase. Herein, high-performance separation of emulsions wastewater was accomplished by developing collagen fibers (CFs)-derived water-oil dual-channels that were comprised of intertwisted superhydrophilic and superhydrophobic CFs. The dual-channels relied on the superhydrophilic CFs to accomplish efficient demulsifying, which played the role as water-channel to enable fast transportation of water, while the superhydrophobic CFs served as the oil-transport channel to permit oil transportation. The mutual repellency between water-channel and oil-channel was essential to guarantee the stability of established dual-channels. The unique dual-channel separation mechanism fundamentally resolved the intercepted phase-caused fouling problem frequently engaged by the superwetting materials that provided single-channel separation capability. Long-lasting (1440 min) anti-fouling separations were achieved by the superwetting CFs-derived dual-channels with separation efficiency high up to 99.99%, and more than 4-fold of stable separation flux as compared with that of superhydrophilic CFs with single-channel separation capability. Our investigations demonstrated a novel strategy by using superwetting CFs to develop water-oil dual-channels for achieving high-performance anti-fouling separation of emulsions wastewater. ENVIRONMENTAL IMPLICATION: Industrial processes discard a large amount of emulsion wastewater, which seriously imperils the aquatic ecosystem. This work demonstrated a conceptual-new strategy to achieve effective remediation of emulsion wastewater via the water-oil dual-channels established by the intertwisted superhydrophilic and superhydrophobic collagen fibers (CFs). The superhydrophilic CFs enabled efficient demulsification of emulsions and played the role of water-channel for the rapid transportation of water, while the superhydrophobic CFs worked as oil-channel to permit the efficient transportation of oil pollutants. Consequently, the long-term (1440 min) anti-fouling high-performance separation of emulsion wastewater was achieved.
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Viscous emulsions with poor fluidity and high adhesion are extremely difficult to separate. Herein, high-flux separation of viscous emulsions is realized by developing structural engineered collagen fibers (CFs)-based composite membrane that featured 3D conductive hierarchical fiber structure with the spaced carbon nanofibers (CNFs) and activated carbon (AC) serving as conductive network and competitive adsorption-based demulsifying sites, respectively. The as-designed membrane structure boosts fast spreading of emulsion droplets on membrane surface aided by the synergistic effect of joule heat in situ generated by the spaced CNFs and the capillary effect derived from CFs, which guarantees the full contact of viscous emulsions with the spaced AC for achieving ultra-efficient demulsifying. The permeation of resultant oily filtrate is accelerated by the capillary effect of hierarchically fibrous structured CFs to exhibit fast transport kinetics, therefore accomplishing high-flux separation. The structural engineered membrane achieves high-performance separation toward different viscous emulsions (55.4-123.7 mPa·s) with separation efficiency >99.9% and flux high up to 259 L m-2 h-1 . The investigations provide a novel structural engineering strategy for realizing high-performance separation of viscous emulsions.
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Pyrethroid insecticides (PIs), a class of structurally similar non-persistent organic pollutants, can be degraded and metabolized to more toxic, and longer half-life products. In this study, the binding interaction mechanisms between human serum albumin (HSA) and the main degradation metabolites of PIs, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), were studied by theoretical simulation and experimental verification. Steady state fluorescence spectra showed that the fluorescence quenching mechanism was static. According to the binding constant, 4-F-3-PBA (1.53 × 105 L mol-1) was bound more strongly to HSA than 3-PBA (1.42 × 105 L mol-1) in subdomain â ¡A (site I). It was found by isothermal titration calorimetry that the metabolites and HSA spontaneously combined mainly through hydrogen bond and van der Waals interaction. Ultraviolet absorption spectra and circular dichroism spectra showed that the metabolites caused slight changes in the microenvironment and conformation of HSA. The above results were proved by molecular docking. The toxicity properties of the metabolites were further analyzed by software, and 4-F-3-PBA was found to be more toxic than 3-PBA. Considering the high exposure level of these metabolites in food, the environment and human body, it is necessary to further explore the toxicity of PIs metabolites.
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Insecticidas , Albúmina Sérica Humana , Humanos , Albúmina Sérica Humana/metabolismo , Simulación del Acoplamiento Molecular , Unión Proteica , Espectrometría de Fluorescencia , Dicroismo Circular , Calorimetría , Sitios de Unión , TermodinámicaRESUMEN
OBJECTIVE: To explore strategies that could reduce coronavirus disease 2019 (COVID-19) vaccine hesitancy in pregnancy. METHODS: In 2021, the authors conducted a survey of pregnant women assessing attitudes and beliefs regarding COVID-19 vaccination. The present analysis reviewed trusted sources of information about COVID-19 vaccination that could reduce vaccine hesitancy among pregnant respondents. RESULTS: A total of 295 surveys were analyzed. Using 10-point Likert scales, intentions to accept COVID-19 vaccine were split between individuals with low (n = 126, 43%) and high (n = 141, 48%) intentions to receive the vaccine, with only a small percentage of women having midrange vaccination intentions (n = 28, 10%). When asked what would reduce their COVID-19 vaccine concerns, published data was the leading answer in both low (46.2%) and medium (35.7%) intention groups followed by personally knowing someone who got vaccinated during pregnancy (21.0% and 28.6% for low and medium groups, respectively). In contrast, an obstetrician's recommendation was the most common answer in the group with high intention to vaccinate (37.2%). Knowing someone who received the vaccine in pregnancy was the leading response for reducing concerns of COVID-19 vaccination among Black respondents. CONCLUSION: The survey identified several innovative and culturally specific approaches to address vaccine confidence and complacency and improve vaccine uptake in pregnant people.
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Vacunas contra la COVID-19 , COVID-19 , Embarazo , Femenino , Humanos , COVID-19/prevención & control , Mujeres Embarazadas , Estudios Prospectivos , VacunaciónRESUMEN
Oil contamination has been an increasingly concerned environmental issue due to the large quantity of oily wastewater discharged by the industry. The extreme wettability-enabled single-channel separation strategy guarantees efficient separation of oil pollutant from wastewater. However, the ultra-high selective permeability forces the intercepted oil pollutant to form a blocking layer, which weakens the separation capability and slows the kinetics of permeable phase. As a consequence, the single-channel separation strategy fails to maintain a stable flux for a long-term separation process. Herein, we reported a brand-new water-oil dual-channels strategy for accomplishing an ultra-stable long-term separation of emulsified oil pollutant from oil-in-water nano-emulsion by engineering two drastically opposite extreme wettabilities (i.e. superhydrophilicity and superhydrophobicity) to build the water-oil dual-channels. The strategy established the superwetting transport channels to permit water and oil pollutant to permeate through their own channel. In this way, the generation of intercepted oil pollutant was prevented, which guaranteed an exceptional long-lasting (20 h) anti-fouling performance for successful achievement of an ultra-stable separation of oil contamination from oil-in-water nano-emulsion with high flux retention and high separation efficiency. Therefore, our investigations provided a new route for realizing ultra-stable long-term separation of emulsified oil pollutant from wastewater.
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INTRODUCTION: Gestational diabetes (GDM) is traditionally thought to emerge from placental endocrine dysregulations, but recent evidence suggests that fetal sex can also impact GDM development. Understanding the molecular mechanisms through which sex modulates placenta physiology can help identify novel molecular targets for future clinical care. Thus, we investigated the nutrient-sensing O-GlcNAc pathway as a potential mediator of sex-specific placenta dysfunction in GDM. METHODS: Expression levels of O-GlcNAc enzymes were measured in male and female (n = 9+/gender) human placentas based on the maternal diagnosis of GDM. We then simulated the observed differences in both BeWo cells and human syncytiotrophoblasts primary cells (SCT) from male and female origins (n = 6/gender). RNA sequencing and targeted qPCR were performed to characterize the subsequent changes in the placenta transcriptome related to gestational diabetes. RESULTS: O-GlcNAc transferase (OGT) expression was significantly reduced only in male placenta collected from mothers with GDM compared to healthy controls. Similar downregulation of OGT in trophoblast-like BeWo male cells demonstrated significant gene expression deregulations that overlapped with known GDM-related genes. Notably, placental growth hormone (GH) production was significantly elevated, while compensatory factors against GH-related insulin resistance were diminished. Inflammatory and immunologic factors with toxic effects on pancreatic ß cell mass were also increased, altogether leaning toward a decompensatory diabetic profile. Similar changes in hormone expression were confirmed in male human primary SCTs transfected with siOGT. However, down-regulating OGT in female primary SCTs did not impact hormone production. CONCLUSION: Our study demonstrated the significant deregulation of placental OGT levels in mothers with GDM carrying a male fetus. When simulated in vitro, such deregulation impacted hormonal production in BeWo trophoblast cells and primary SCTs purified from male placentas. Interestingly, female placentas were only modestly impacted by OGT downregulation, suggesting that the sex-specific presentation observed in gestational diabetes could be related to O-GlcNAc-mediated regulation of placental hormone production.
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Diabetes Gestacional , Placenta , Embarazo , Femenino , Masculino , Humanos , Placenta/metabolismo , Diabetes Gestacional/metabolismo , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/metabolismo , Insulina/metabolismoRESUMEN
AIMS: While women with gestational diabetes mellitus (GDM) have a higher risk of developing type 2 diabetes mellitus (T2DM) and at a younger age, it is unknown whether T2DM following GDM is associated with worse clinical outcomes. This study aims to examine the impact of GDM on subsequent development of long-term complications of T2DM. METHODS: All women with T2DM from the National Health and Nutrition Examination Survey (NHANES), a nationally representative cross-sectional survey of US population, between 2007 and 2018 (n = 2494) were stratified into two groups: those with a history of GDM (n = 385) and those without (n = 2109). Rates of macrovascular and microvascular complications of T2DM were compared between the two groups using bivariate and multivariate analyses. RESULTS: Of 2494 participants with T2DM included in the analysis, 385 (15.4 %) had a history of GDM and 2109 (84.6 %) did not. A history of GDM was independently associated with increased risk of myocardial infarction (aOR 2.53, 95%Cl: 1.18-5.40) and likely coronary artery disease (aOR 2.15, 95 % Cl: 1.00-4.66). CONCLUSIONS: In this cohort, women with T2DM and a history of GDM had higher risk of macrovascular complications of myocardial infarction and coronary artery disease, compared to those with no history of gestational diabetes.
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Enfermedad de la Arteria Coronaria , Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Infarto del Miocardio , Enfermedad de la Arteria Coronaria/complicaciones , Estudios Transversales , Complicaciones de la Diabetes/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Femenino , Humanos , Infarto del Miocardio/complicaciones , Encuestas Nutricionales , Embarazo , Factores de RiesgoRESUMEN
Accurate prediction of crude oil prices (COPs) is a challenge for academia and industry. Therefore, the present research developed a new CEEMDAN-GA-SVR hybrid model to predict COPs, incorporating complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), a genetic algorithm (GA), and support vector regression machine (SVR). First, our team utilized CEEMDAN to realize the decomposition of a raw series of COPs into a group of comparatively simpler subseries. Second, SVR was utilized to predict values for every decomposed subseries separately. Owing to the intricate parametric settings of SVR, GA was employed to achieve the parametric optimisation of SVR during forecast. Then, our team assembled the forecasted values of the entire subseries as the forecasted values of the CEEMDAN-GA-SVR model. After a series of experiments and comparison of the results, we discovered that the CEEMDAN-GA-SVR model remarkably outperformed single and ensemble benchmark models, as displayed by a case study finished based on a time series of weekly Brent COPs.
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Petróleo , Máquina de Vectores de Soporte , PredicciónRESUMEN
The paper intends to optimize the landscape of the agricultural and animal husbandry (AG and AH) production park using the deep reinforcement learning (DRL) model under circular symbiosis. Therefore, after reviewing the relevant literature, decision tree evolutionary algorithm, and ensemble learning criteria, this paper studies and constructs the circular symbiotic industrial chain. Then, an experiment of landscaping the park and optimizing the production is made with full consideration of practical institutions. Finally, the numerical results show that the yield of several crops has been significantly improved after the landscape optimization by the proposed DRL model. Remarkably, the increase in rice yield is the most prominent. The yield of rice and wheat was about 12 kg before optimization and 18 kg after DRL model optimization, which has increased by 6 kg. This research has important reference value for improving the output efficiency of AG and AH products.
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Oryza , Simbiosis , Crianza de Animales Domésticos , Animales , Productos Agrícolas , Refuerzo en PsicologíaRESUMEN
Neural innervations exert essential roles in the prostate. However, spatial distribution and regulatory function of such neural inputs are incompletely characterized. Here, we exploited the advanced whole-tissue immunolabeling and optical clearing technique to assess the 3D anatomy of autonomic innervations in the mouse and human prostate for the first time. We observed that sympathetic and parasympathetic inputs in the mouse prostate remained unaffected during castration-induced tissue regression. However, the pharmacologic destruction of sympathetic innervations in the mouse prostate led to sterile inflammation of the tissue, mimicking the disease condition of chronic non-bacterial prostatitis. Also, the genetic ablation of sympathetic inputs produced a similar inflammatory response. Furthermore, we showed that treatment of the specific ß2-adrenergic receptor agonists could effectively mitigate the prostate inflammation caused by such sympathetic loss. Together, these results have elucidated the new immunomodulatory function of the sympathetic signal via the ß2-adrenergic receptor in prostate inflammatory disease.
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Membrane separation is a promising approach for the remediation of oil contamination in water. High-flux separation of membrane relies on the rational design of ultrathin active layer to significantly reduce mass transfer distance for achieving high separation flux, while the ultrathin active layer is usually fragile with poor mechanical strength, which has to be supported on a support. Herein, we employed collagen fiber membrane (CFM) as multi-functional support for the in-situ growth of polyacrylonitrile (PAN) layer by electrospinning to prepare the high-performance PAN/CFM composite membrane. Due to the amphiphilic nature and strong capillary effect, CFM played the role as multi-functional support to provide separation effectiveness and boosted separation flux. The PAN/CFM composite membrane enabled ultrahigh separation flux (e.g., 51751.59 L m-2 h-1 bar-1) to a variety of oil-in-water emulsion, which was one order of magnitude higher than that of commercial polyethersulfone membrane and 1.86-fold to that of cellulose acetate membrane. Furthermore, the PAN/CFM composite membrane retained high separation flux (e.g., 11046.97 L m-2 h-1 bar-1) during the 5th separation cycle, providing appreciable anti-fouling capability. Therefore, our findings provided a promising way to effectively resolve the problem of oil contamination in water.
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Colágeno , Contaminación por Petróleo , Contaminantes Químicos del Agua , Purificación del Agua , Aceites , Agua , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
Separation plays a critical role in a broad range of industrial applications. Developing advanced separation materials is of great significance for the future development of separation technology. Collagen fibers (CFs), the typical structural proteins, exhibit unique structural hierarchy, amphiphilic wettability, and versatile chemical reactivity. These distinctive properties provide infinite possibilities for the rational design of advanced separation materials. During the past 2 decades, many progressive achievements in the development of CFs-derived advanced separation materials have been witnessed already. Herein, the CFs-based separation materials are focused on and the recent progresses in this topic are reviewed. CFs widely existing in animal skins display unique hierarchically fibrous structure, amphiphilicity-enabled surface wetting behaviors, multi-functionality guaranteed covalent/non-covalent reaction versatility. These outstanding merits of CFs bring great opportunities for realizing rational design of a variety of advanced separation materials that were capable of achieving high-performance separations to diverse specific targets, including oily pollutants, natural products, metal ions, anionic contaminants and proteins, etc. Besides, the important issues for the further development of CFs-based advanced separation materials are also discussed.
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Animales , Humectabilidad , Aceites/química , ColágenoRESUMEN
The environmental and dietary pesticide exposures can cause thyroid hormones (THs) disorders, which are associated with the high incidence of thyroid diseases worldwide. The structures of diphenyl ether pesticides and their metabolites are very similar to the structure of THs. Based on this, in silico molecular simulation approaches were used to predict, screen, evaluate and identify the binding interactions of 98 diphenyl ether structure pesticides and their metabolites (DEPMs) with 10 THs related proteins in the study. The research results indicated that these DEPMs such as fluoroglycofen (FOG), rafoxanide, diclofop, ethoxyfen and difenopenten were considered to have the greater potentials to interfere with the related proteins of THs biosynthesis, blood transport, receptor binding and metabolism. And FOG can interact with thyroid hormone receptor beta (TRß) to form non-bond interactions. Furthermore, the results of molecular dynamics simulations showed that there were strong and stable interactions between FOG and TRß. These results suggested that the herbicide FOG was likely to disturb THs nuclear receptor. And benzene rings and hydrophobic groups might be the characteristic chemical functional groups for DEPMs to disrupt TRß. The relevant results of this study can be used to provide references for environmental toxicology evaluation, food safety risk assessment, and formulation and revision of pesticides and their metabolites residue limits in agricultural products and food.
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Ecotoxicología , Plaguicidas , Plaguicidas/toxicidad , Éteres Fenílicos , Hormonas TiroideasRESUMEN
BACKGROUND: Brain astroglia are activated preceding the onset of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We characterized the effects of brain astroglia on spinal cord inflammation, focusing on astroglial connexin (Cx)43, because we recently reported that Cx43 has a critical role in regulating neuroinflammation. METHODS: Because glutamate aspartate transporter (GLAST)+ astroglia are enriched in the brain gray matter, we generated Cx43fl/fl;GLAST-CreERT2/+ mice that were brain gray matter astroglia-specific Cx43 conditional knockouts (Cx43 icKO). EAE was induced by immunization with myelin oligodendroglia glycoprotein (MOG) 35-55 peptide 10 days after tamoxifen injection. Cx43fl/fl mice were used as controls. RESULTS: Acute and chronic EAE signs were significantly milder in Cx43 icKO mice than in controls whereas splenocyte MOG-specific responses were unaltered. Histologically, Cx43 icKO mice showed significantly less demyelination and fewer CD45+ infiltrating immunocytes, including F4/80+ macrophages, and Iba1+ microglia in the spinal cord than controls. Microarray analysis of the whole cerebellum revealed marked upregulation of anti-inflammatory A2-specific astroglia gene sets in the pre-immunized phase and decreased proinflammatory A1-specific and pan-reactive astroglial gene expression in the onset phase in Cx43 icKO mice compared with controls. Astroglia expressing C3, a representative A1 marker, were significantly decreased in the cerebrum, cerebellum, and spinal cord of Cx43 icKO mice compared with controls in the peak phase. Isolated Cx43 icKO spinal microglia showed more anti-inflammatory and less proinflammatory gene expression than control microglia in the pre-immunized phase. In particular, microglial expression of Ccl2, Ccl5, Ccl7, and Ccl8 in the pre-immunized phase and of Cxcl9 at the peak phase was lower in Cx43 icKO than in controls. Spinal microglia circularity was significantly lower in Cx43 icKO than in controls in the peak phase. Significantly lower interleukin (IL)-6, interferon-γ, and IL-10 levels were present in cerebrospinal fluid from Cx43 icKO mice in the onset phase compared with controls. CONCLUSIONS: The ablation of Cx43 in brain gray matter astroglia attenuates EAE by promoting astroglia toward an anti-inflammatory phenotype and suppressing proinflammatory activation of spinal microglia partly through depressed cerebrospinal fluid proinflammatory cytokine/chemokine levels. Brain astroglial Cx43 might be a novel therapeutic target for MS.
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Astrocitos/metabolismo , Conexina 43/deficiencia , Conexina 43/genética , Enfermedades Desmielinizantes , Sustancia Gris/metabolismo , Enfermedades Neuroinflamatorias , Médula Espinal/patología , Animales , Astrocitos/patología , Quimiocinas/líquido cefalorraquídeo , Conexina 43/metabolismo , Citocinas/líquido cefalorraquídeo , Enfermedades Desmielinizantes/etiología , Enfermedades Desmielinizantes/fisiopatología , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/genética , Expresión Génica , Sustancia Gris/patología , Ratones , Ratones Noqueados , Esclerosis Múltiple/fisiopatología , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/genética , Enfermedades Neuroinflamatorias/fisiopatología , Médula Espinal/inmunologíaRESUMEN
The α-type ADP-ribosylated peptides represent a class of important molecular tools in the field of protein ADP-ribosylation, however, they are difficult to access because of their inherent complicated structures and the lack of effective synthetic tools. In this paper, we present a biomimetic α-selective ribosylation reaction to synthesize a key intermediate, α-ADP-ribosyl azide, directly from native ß-nicotinamide adenine dinucleotide in a clean ionic liquid system. This reaction in tandem with click chemistry then offers a two-step modular synthesis of α-ADP-ribosylated peptides. These syntheses can be performed open air in eppendorf tubes, without the need for specialized instruments or training. Importantly, we demonstrate that the synthesized α-ADP-ribosylated peptides show high binding affinity and desirable stability for enriching protein partners, and reactivity in post-stage poly ADP-ribosylations. Owing to their simple chemistry and multidimensional bio-applications, the presented methods may provide a powerful platform to produce general molecular tools for the study of protein ADP-ribosylation.
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Adenosina Difosfato Ribosa/química , Materiales Biomiméticos/síntesis química , Péptidos/síntesis química , ADP-Ribosilación , Materiales Biomiméticos/química , Materiales Biomiméticos/metabolismo , Catálisis , Química Clic , Histonas/metabolismo , Líquidos Iónicos/química , NAD/química , Péptidos/química , Péptidos/metabolismo , Unión ProteicaRESUMEN
In multiple sclerosis plaques, oligodendroglial connexin (Cx) 47 constituting main gap junction channels with astroglial Cx43 is persistently lost. As mice with Cx47 single knockout exhibit no demyelination, the roles of Cx47 remain undefined. We aimed to clarify the effects of oligodendroglia-specific Cx47 inducible conditional knockout (icKO) on experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein peptide (MOG35-55) in PLP/CreERT;Cx47fl/fl mice at 14 d after tamoxifen injection. Cx47 icKO mice demonstrated exacerbation of acute and chronic relapsing EAE with more pronounced demyelination than Cx47 flox (fl)/fl littermates. CD3+ T cells more abundantly infiltrated the spinal cord in Cx47 icKO than in Cx47 fl/fl mice throughout the acute to chronic phases. CXCR3-CCR6+CD4+ and IL17+IFNγ-CD4+ helper T (Th) 17 cells isolated from spinal cord and brain tissues were significantly increased in Cx47 icKO mice compared with Cx47 fl/fl mice, while MOG35-55-specific proliferation and proinflammatory cytokine production of splenocytes were unaltered. Microarray analysis of isolated microglia revealed stronger microglial activation toward proinflammatory and injury-response phenotypes with increased expressions of chemokines that can attract Th17 cells, including Ccl2, Ccl3, Ccl4, Ccl7, and Ccl8, in Cx47 icKO mice compared with Cx47 fl/fl mice. In Cx47 icKO mice, NOS2+ and MHC class II+ microglia were more enriched immunohistochemically, and A1-specific astroglial gene expressions and astroglia immunostained for C3, a representative A1 astrocyte marker, were significantly increased at the acute phase, compared with Cx47 fl/fl mice. These findings suggest that oligodendroglia-specific Cx47 ablation induces severe inflammation upon autoimmune demyelination, underscoring a critical role for Cx47 in regulating neuroinflammation.
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Conexinas/inmunología , Esclerosis Múltiple/inmunología , Oligodendroglía/inmunología , Animales , Quimiocinas/genética , Quimiocinas/inmunología , Conexinas/genética , Enfermedades Desmielinizantes , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Noqueados , Esclerosis Múltiple/genética , Vaina de Mielina/genética , Vaina de Mielina/inmunología , Médula Espinal/inmunología , Células Th17/inmunologíaRESUMEN
Objective To assess maternal thyroid-stimulating immunoglobulin (TSI) as a predictor of neonatal thyroid hyperthyroidism in pregnancies complicated by Graves' disease. Methods This is a 10-year retrospective study of patients with a history of Graves' disease and elevated TSI activity level defined as 1.3 times the normal. All subjects underwent cordocentesis for ultrasound findings of suspected fetal thyrotoxicosis (fetal tachycardia, oligohydramnios, hydrops, and thyromegaly). Neonatal diagnosis was made based on neonatal thyroid function testing or symptoms. Results Fourteen patients were included in the study, seven with active Graves' disease requiring antithyroid drug ("ATD group") and seven with iatrogenic hypothyroidism on levothyroxine ("levothyroxine group"). Four cases (57%) of neonatal thyrotoxicosis were diagnosed in the levothyroxine group compared with two cases (28%) in the ATD group. The lowest maternal TSI level at which a neonate did not develop hyperthyroidism was 2.6 for the levothyroxine group and 2.5 for the ATD group. The odds ratio of a neonate from the levothyroxine group developing hyperthyroidism compared with one from the ATD group is 3.3 (95% confidence interval: 0.4-30.7). Conclusion For patients with Graves' disease, those with iatrogenic hypothyroidism and TSI > 2.5 times the basal level are at the highest risk for neonatal thyrotoxicosis.
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Objective: Immunoglobulin (Ig)G4-related disease is a major cause of hypertrophic pachymeningitis (HP), presenting as a progressive thickening of the dura mater. HP lacks an animal model to determine its underlying mechanisms. We developed a suitable animal model for the treatment of HP. Methods: We longitudinally evaluated dura in mice with a mutation (Y136F) in the linker for activation of T cells (LAT), which induced type 2 T helper (Th2) cell proliferation and IgG1 (IgG4 human equivalent) overexpression. Mice were therapeutically administered daily oral irbesartan from 3 to 6 weeks of age. Human IgG4-related, anti-neutrophil cytoplasmic antibody-related, and idiopathic HP dura were also immunohistochemically examined. Results: LATY136F mice showing dural gadolinium enhancement on magnetic resonance imaging had massive infiltration of B220+ B cells, IgG1+ cells, CD138+ plasma cells, CD3+ T cells, F4/80+ macrophages, and polymorphonuclear leukocytes in the dura at 3 weeks of age, followed by marked fibrotic thickening. In dural lesions, transforming growth factor (TGF)-ß1 was produced preferentially in B cells and macrophages while TGF-ß receptor I (TGF-ß RI) was markedly upregulated on fibroblasts. Quantitative western blotting revealed significant upregulation of TGF-ß1, TGF-ß RI, and phosphorylated SMAD2/SMAD3 in dura of LATY136F mice aged 13 weeks. A similar upregulation of TGF-ß RI, SMAD2/SMAD3, and phosphorylated SMAD2/SMAD3 was present in autopsied dura of all three types of human HP. Irbesartan abolished dural inflammatory cell infiltration and fibrotic thickening in all treated LATY136F mice with reduced TGF-ß1 and nonphosphorylated and phosphorylated SMAD2/SMAD3. Interpretation: TGF-ß1/SMAD2/SMAD3 pathway is critical in HP and is a potential novel therapeutic target.
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Duramadre/patología , Meningitis/tratamiento farmacológico , Meningitis/fisiopatología , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Animales , Duramadre/efectos de los fármacos , Duramadre/inmunología , Fibrosis , Humanos , Hipertrofia , Inflamación , Irbesartán/farmacología , Proteínas de la Membrana/deficiencia , Meningitis/metabolismo , Ratones , Ratones Transgénicos , Modelos Animales , Fosforilación , Transducción de Señal , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Hypertrophic pachymeningitis (HP) is a rare neurologic disease causing inflammatory fibrous thickening of the brain and spinal dura mater. We investigated the cerebrospinal fluid cytokine profile of HP by measuring 28 cytokines/chemokines/growth factors with a multiplexed fluorescent immunoassay in 8 patients with HP (6 idiopathic, 1 IgG4-related, 1 anti-neutrophil cytoplasmic antibody-related), and 11 with other non-inflammatory neurologic diseases (OND). Interleukin (IL)-4, IL-5, IL-9, IL-10, TNF-α, and CXCL8/IL-8 levels were significantly higher in idiopathic HP (IHP) than OND. Cluster analyses disclosed two major clusters: one mainly consisted of IHP and the other of OND, suggesting a unique cytokine profile in IHP.