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The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1ß was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1ß or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1ß-mediated comorbidities, offering a framework for secondary prevention immunotherapy.
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Lesiones Encefálicas , Inmunidad Innata , Memoria Inmunológica , Inflamación , Interleucina-1beta , Ratones Endogámicos C57BL , Monocitos , Animales , Ratones , Interleucina-1beta/metabolismo , Lesiones Encefálicas/inmunología , Humanos , Masculino , Monocitos/metabolismo , Monocitos/inmunología , Inflamación/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/inmunología , Cardiopatías/inmunología , Femenino , Receptores CCR2/metabolismo , Fibrosis , Epigénesis Genética , Inmunidad EntrenadaRESUMEN
Loss of lymphocytes, particularly T cell apoptosis, is a central pathological event after severe tissue injury that is associated with increased susceptibility for life-threatening infections. The precise immunological mechanisms leading to T cell death after acute injury are largely unknown. Here, we identified a monocyte-T cell interaction driving bystander cell death of T cells in ischemic stroke and burn injury. Specifically, we found that stroke induced a FasL-expressing monocyte population, which led to extrinsic T cell apoptosis. This phenomenon was driven by AIM2 inflammasome-dependent interleukin-1ß (IL-1ß) secretion after sensing cell-free DNA. Pharmacological inhibition of this pathway improved T cell survival and reduced post-stroke bacterial infections. As such, this study describes inflammasome-dependent monocyte activation as a previously unstudied cause of T cell death after injury and challenges the current paradigms of post-injury lymphopenia.
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Coinfección/inmunología , Proteínas de Unión al ADN/inmunología , Tolerancia Inmunológica/inmunología , Inflamasomas/inmunología , Transducción de Señal/inmunología , Animales , Apoptosis/inmunología , Infecciones Bacterianas/inmunología , Quemaduras/inmunología , Quemaduras/microbiología , Coinfección/microbiología , Humanos , Interleucina-1beta/inmunología , Ratones , Ratones Endogámicos C57BL , Monocitos/inmunología , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/microbiología , Linfocitos T/inmunologíaRESUMEN
The risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies1. Risk is particularly high in patients with atherosclerosis, with more than 10% of patients experiencing early recurrent events1,2. However, despite the enormous medical burden of this clinical phenomenon, the underlying mechanisms leading to increased vascular risk and recurrent stroke are largely unknown. Here, using a novel mouse model of stroke-induced recurrent ischaemia, we show that stroke leads to activation of the AIM2 inflammasome in vulnerable atherosclerotic plaques via an increase of circulating cell-free DNA. Enhanced plaque inflammation post-stroke results in plaque destabilization and atherothrombosis, finally leading to arterioarterial embolism and recurrent stroke within days after the index stroke. We confirm key steps of plaque destabilization also after experimental myocardial infarction and in carotid artery plaque samples from patients with acute stroke. Rapid neutrophil NETosis was identified as the main source of cell-free DNA after stroke and NET-DNA as the causative agent leading to AIM2 inflammasome activation. Neutralization of cell-free DNA by DNase treatment or inhibition of inflammasome activation reduced the rate of stroke recurrence after experimental stroke. Our findings present an explanation for the high recurrence rate after incident ischaemic events in patients with atherosclerosis. The detailed mechanisms uncovered here provide clinically uncharted therapeutic targets for which we show high efficacy to prevent recurrent events. Targeting DNA-mediated inflammasome activation after remote tissue injury represents a promising avenue for further clinical development in the prevention of early recurrent events.
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Fine particulates (FPs) are a major class of airborne pollutants. In mammals, FPs may reach the alveoli through the respiratory system, cross the air-blood barrier, spread into other organs, and induce hazardous effects. Although birds have much higher respiratory risks to FPs than mammals, the biological fate of inhaled FPs in birds has rarely been explored. Herein, we attempted to disclose the key properties that dictate the lung penetration of nanoparticles (NPs) by visualizing a library of 27 fluorescent nanoparticles (FNPs) in chicken embryos. The FNP library was prepared by combinational chemistry to tune their compositions, morphologies, sizes, and surface charges. These NPs were injected into the lungs of chicken embryos for dynamic imaging of their distributions by IVIS Spectrum. FNPs with diameters <16 nm could cross the air-blood barrier in 20 min, spread into the blood, and accumulate in the yolk sac. In contrast, large FNPs (>30 nm) were mainly retained in the lungs and rarely detected in other tissues/organs. In addition to size, surface charge was the secondary determinant for NPs to cross the air-blood barrier. Compared to cationic and anionic particles, neutrally charged FNPs showed the fastest lung penetration. A predictive model was therefore developed to rank the lung penetration capability of FNPs by in silico analysis. The in silico predictions could be well validated in chicks by oropharyngeal exposure to six FNPs. Overall, our study discovered the key properties of NPs that are responsible for their lung penetration and established a predictive model that will greatly facilitate respiratory risk assessments of nanoproducts.
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Pollos , Nanopartículas , Embrión de Pollo , Animales , Barrera Alveolocapilar , Nanopartículas/química , Pulmón , Colorantes , Tamaño de la Partícula , MamíferosRESUMEN
INTRODUCTION: Small airway dysfunction (SAD) is associated with type 2 inflammation in patients who have non-asthmatic chronic rhinosinusitis with nasal polyps (CRSwNPs); however, the risk factors for abnormal small airway function indicators in CRSwNP patients with and without asthma remain unclear. METHODS: We retrospectively analyzed 41 asthmatic and 109 non-asthmatic CRSwNP patients. Clinical characteristics were compared between groups, correlations between small airway function and clinical parameters were calculated, and independent risk factors for every small airway indicator were identified in each group. RESULTS: Asthmatic CRSwNP patients had significantly reduced small airway function, and the proportion of patients with SAD was higher in asthmatic CRSwNP patients (65.85%) than in patients without asthma (9.17%). With regard to specific airway function indicators, age and a patient's blood eosinophil (%) were identified as independent risk factors for lower FEF50% %pred and FEF25-75% pred, with age being an independent risk factor for FEF75% %pred in asthmatic CRSwNP patients. In non-asthmatic CRSwNP patients, allergic rhinitis comorbidity was found to be an independent risk factor for FEF50% %pred, FEF75% %pred, and FEF25-75% %pred. CONCLUSION: Physicians should pay greater attention to risk factors for abnormal small airway function indicators in patients with CRSwNPs to prevent the occurrence of SAD.
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Asma , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/epidemiología , Estudios Retrospectivos , Rinitis/complicaciones , Rinitis/epidemiología , Asma/complicaciones , Asma/epidemiología , Sinusitis/complicaciones , Sinusitis/epidemiología , Factores de Riesgo , Enfermedad CrónicaRESUMEN
Background: Allergic asthma accounts for the majority of childhood asthma and is characterized by elevated total serum immunoglobulin E (tIgE). However, whether tIgE can predict allergic asthma in childhood asthma remains unclear. Objective: The purpose of this study was to identify the potential of tIgE for predicting allergic asthma in childhood asthma and provide a reliable reference value. Methods: Clinical characteristics and the level of tIgE from children with asthma in 2008 (n = 280) and 2018 (n = 479) were retrospectively analyzed. Receiver operating characteristic (ROC) curves were generated to determine the optimal cutoff points and predictive values of tIgE for diagnosing allergic asthma in childhood asthma in 2008 and 2018, and the diagnosis efficiency of tIgE was validated in 491 children with asthma of 2019. Results: The level of tIgE was significantly lower in 2018 than that in 2008. Receiver operating characteristic curves showed cutoff values of tIgE were 142.50 IU/mL (area under the curve [AUC] = 0.864) and 96.25 IU/mL (AUC = 0.835) for diagnosing allergic asthma in 2008 and 2018, respectively. The level of tIgE from children with asthma in 2019 was similar to that in 2018 but was significantly lower than that in 2008. We further used the cutoff value of tIgE = 96.25 IU/mL to validate the diagnosis efficiency in children with asthma of 2019 and found that the diagnostic accuracy, sensitivity, specificity of allergic asthma, and the Youden index reached 76.78%, 76.10%, 78.03%, and 0.540, respectively. Conclusion: The tIgE value is an effective predictor for diagnosing allergic asthma in childhood asthma, with tIgE = 96.25 IU/mL being the recommended limit.
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Asma , Niño , Humanos , Estudios Retrospectivos , Asma/diagnóstico , Inmunoglobulina E , Curva ROC , Valores de ReferenciaRESUMEN
The WRKY transcription factor (TF) family is one the largest plant-specific transcription factor families. It has been proven to play significant roles in multiple plant biological processes, especially stress response. Although many WRKY TFs have been identified in various plant species, WRKYs in white birch (Betula platyphylla Suk.) remain to be studied. Here, we identified a total of 68 BpWRKYs, which could be classified into four main groups. The basic physiochemical properties of these TFs were analyzed using bioinformatics tools, including molecular weight, isoelectric point, chromosome location, and predicted subcellular localization. Most BpWRKYs were predicted to be located in the nucleus. Synteny analysis found 17 syntenic gene pairs among BpWRKYs and 52 syntenic gene pairs between BpWRKYs and AtWRKYs. The cis-acting elements in the promoters of BpWRKYs could be enriched in multiple plant biological processes, including stress response, hormone response, growth and development, and binding sites. Tissue-specific expression analysis using qRT-PCR showed that most BpWRKYs exhibited highest expression levels in the root. After ABA, salt (NaCl), or cold treatment, different BpWRKYs showed different expression patterns at different treatment times. Furthermore, the results of the Y2H assay proved the interaction between BpWRKY17 and a cold-responsive TF, BpCBF7. By transient expression assay, BpWRKY17 and BpWRKY67 were localized in the nucleus, consistent with the previous prediction. Our study hopes to shed light for research on WRKY TFs and plant stress response.
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Proteínas de Plantas , Factores de Transcripción , Factores de Transcripción/metabolismo , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Betula/genética , Betula/metabolismo , Regulación de la Expresión Génica de las Plantas , FilogeniaRESUMEN
Biofilm formation is a major threat to industry, the environment and human health. While killing of embedded microbes in biofilms may inevitably lead to the evolution of antimicrobial resistance (AMR), catalytic quenching of bacterial communications by lactonase is a promising antifouling approach. Given the shortcomings of protein enzymes, it is attractive to engineer synthetic materials to mimic the activity of lactonase. Herein, an efficient lactonase-like Zn-Nx -C nanomaterial was synthesized by tuning the coordination environment around zinc atoms to mimic the active domain of lactonase for catalytical interception of bacterial communications in biofilm formation. The Zn-Nx -C material could selectively catalyze 77.5 % hydrolysis of N-acylated-L-homoserine lactone (AHL), a critical bacterial quorum sensing (QS) signal in biofilm construction. Consequently, AHL degradation downregulated the expression of QS-related genes in antibiotic resistant bacteria and significantly prevented biofilm formation. As a proof of concept, Zn-Nx -C-coated iron plates prevented 80.3 % biofouling after a month exposure in river. Overall, our study provides a nano-enabled contactless antifouling insight to avoid AMR evolution by engineering nanomaterials for mimicking the key bacterial enzymes (e.g., lactonase) functioning in biofilm construction.
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Biopelículas , Percepción de Quorum , Humanos , Bacterias/metabolismo , Acil-Butirolactonas/metabolismo , Proteínas Bacterianas/metabolismoRESUMEN
As an emerging pollutant in the life cycle of plastic products, micro/nanoplastics (M/NPs) are increasingly being released into the natural environment. Substantial concerns have been raised regarding the environmental and health impacts of M/NPs. Although diverse M/NPs have been detected in natural environment, most of them display two similar features, i.e.,high surface area and strong binding affinity, which enable extensive interactions between M/NPs and surrounding substances. This results in the formation of coronas, including eco-coronas and bio-coronas, on the plastic surface in different media. In real exposure scenarios, corona formation on M/NPs is inevitable and often displays variable and complex structures. The surface coronas have been found to impact the transportation, uptake, distribution, biotransformation and toxicity of particulates. Different from conventional toxins, packages on M/NPs rather than bare particles are more dangerous. We, therefore, recommend seriously consideration of the role of surface coronas in safety assessments. This review summarizes recent progress on the eco-coronas and bio-coronas of M/NPs, and further discusses the analytical methods to interpret corona structures, highlights the impacts of the corona on toxicity and provides future perspectives.
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Contaminantes Ambientales , Nanopartículas , Microplásticos , Nanopartículas/toxicidad , Medición de RiesgoRESUMEN
BACKGROUND: Aspiration pneumonitis is an inflammatory disease of the lungs which is difficult to diagnose accurately. Large-volume aspiration of oropharyngeal or gastric contents is essential for the development of aspiration pneumonitis. The role of cerebrospinal fluid (CSF) rhinorrhea is often underestimated as a rare etiological factor for aspiration in the diagnosis process of aspiration pneumonitis. CASE PRESENTATION: We present a case of a patient with 4 weeks of right-sided watery rhinorrhea accompanied by intermittent postnasal drip and dry cough as the main symptoms. Combined with clinical symptoms, imaging examination of the sinuses, and laboratory examination of nasal secretions, she was initially diagnosed as spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, and intraoperative endoscopic findings and postoperative pathology also confirmed this diagnosis. Her chest computed tomography showed multiple flocculent ground glass density shadows in both lungs on admission. The patient underwent endoscopic resection of meningoencephalocele and repair of skull base defect after she was ruled out of viral pneumonitis. Symptoms of rhinorrhea and dry cough disappeared, and pneumonitis was improved 1 week after surgery and cured 2 months after surgery. Persistent CSF rhinorrhea caused by spontaneous sphenoid sinus meningoencephalocele was eventually found to be a major etiology for aspiration pneumonitis although the absence of typical symptoms and well-defined risk factors for aspiration, such as dysphagia, impaired cough reflex and reflux diseases. CONCLUSIONS: We report a rare case of aspiration pneumonitis caused by spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, which can bring more attention and understanding to the uncommon etiology for aspiration, so as to make more accurate diagnosis of the disease and early surgical treatment.
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Rinorrea de Líquido Cefalorraquídeo/complicaciones , Encefalocele/complicaciones , Meningocele/complicaciones , Neumonía por Aspiración/etiología , Seno Esfenoidal/patología , Rinorrea de Líquido Cefalorraquídeo/diagnóstico , Rinorrea de Líquido Cefalorraquídeo/patología , Rinorrea de Líquido Cefalorraquídeo/cirugía , Encefalocele/diagnóstico , Encefalocele/cirugía , Endoscopía , Femenino , Humanos , Pulmón/diagnóstico por imagen , Meningocele/diagnóstico , Meningocele/cirugía , Persona de Mediana Edad , Neumonía por Aspiración/diagnóstico , Neumonía por Aspiración/cirugía , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/patología , Base del Cráneo/cirugía , Seno Esfenoidal/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
A facile synthesis is reported of two-dimensional (2D) bimetallic (Fe/Co=1:2) metal-organic frameworks (MOF, ca. 2.2â nm thick) via simple stirring of the reaction mixture of Fe/Co salts and 1,4-benzene dicarboxylic acid (1,4-BDC) in the presence of triethylamine and water at room temperature. The mechanism of the 2D, rather than bulk, MOF was revealed by studying the role of each component in the reaction mixture. It was found that these 2D MOF-Fe/Co(1:2) exhibited excellent electrocatalytic activity for the oxygen evolution reaction (OER) under basic conditions. The electrocatalytic mechanism was disclosed via both experimental results and density functional theory (DFT) calculation. The 2D morphology and co-doping of Fe/Co contributed to the superior OER performance of the 2D MOF-Fe/Co(1:2). The simple and efficient synthetic method is suitable for the mass production and future commercialization of functional 2D MOF with low cost and high yield.
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The leaves and roots of Liriope muscari (Decne.) Baily were subjected to high-throughput Illumina transcriptome sequencing. Bioinformatics analysis was used to investigate the enzyme genes and key transcription factors involved in regulating the accumulation of steroidal saponins, which are the main active ingredient in L. muscari. These analyses aimed to reveal the molecular mechanism behind steroidal saponin accumulation. The sequencing results of L. muscari revealed 31 enzymes, including AACT, CAS, DXS and DXR, that are involved in the synthesis of steroidal saponins. Among these enzymes, 16 were in the synthesis of terpenoid skeleton, 3 were involved in the synthesis of sesquiterpene and triterpene, and 12 were involved in the synthesis of steroidal compound. Differential gene expression identified 15 metabolic enzymes coded by 34 differentially expressed genes (DEGs) in the leaves and roots, which were associated with steroidal saponin synthesis. Further analysis using gene co-expression patterns showed that 14 metabolic enzymes coded by 31 DEGs were co-expressed. In addition, analysis using gene co-expression analysis and PlantTFDB's transcription factor analysis tool predicted the involvement of 8 transcription factors, including GAI, PIF4, PIL6, ERF8, SVP, LHCA4, NF-YB3 and DOF2.4, in regulating 6 metabolic enzymes such as DXS, DXR, HMGR, DHCR7, DHCR24, and CAS. These eight transcription factors were predicted to play important roles in regulating steroidal saponin accumulation in L. muscari. Promoter analysis of these transcription factors indicated that their main regulatory mechanisms involve processes such as abscisic acid response, drought-induction stress response and light response, especially abscisic acid responsive elements (ABRE) response and MYB binding site involved in drought-inducibility (MBS) response pathway. Furthermore, qRT-PCR analysis of these eight key transcription factors demonstrated their specific differences in the leaves and roots.
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Biología Computacional , Liriope (Planta) , Hojas de la Planta , Saponinas , Factores de Transcripción , Transcriptoma , Saponinas/metabolismo , Saponinas/biosíntesis , Biología Computacional/métodos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Liriope (Planta)/genética , Liriope (Planta)/metabolismo , Esteroides/metabolismo , Esteroides/biosíntesis , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Regulación de la Expresión Génica de las Plantas , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Aiming to decrease the recurrence of tumors and achieve patient satisfaction, the elicitation of immunotherapy and its integrated synergistic employment is a bright new direction in oncotherapy, yet an emergently challenging task. In particular, tumor-associated macrophage (TAM) regulation though light-induced photodynamic and photothermal therapy (PDT and PTT) is regarded as a powerful approach, which focuses on the systemic immune system instead of the tumor itself. Herein, this study reports an acceptor-donor-acceptor (A-D-A) aggregation-induced emission luminogen (AIEgen), named TPA-2CN, which was applied as a photosensitizer (PS) and photothermal agent (PTA). Attributed to its A-D-A structure and AIE properties, TPA-2CN exhibits a high molar absorption coefficient and acts as a perfect template in regulating radiative and nonradiative transitions, which mainly utilize excited energy. The generation of type I reactive oxygen promoted its application in hypoxic tumor sites and the combination of hyperpyrexia forcefully induces macrophages to polarize towards the immune response M1 phenotype. In in vitro and in vivo, the successful reversion and reprogramming of the immune microenvironment was impressively proved. This method optimally concentrated immune therapy, PDT and PTT as one and exhibited excellent synergistic therapeutic effects with good biosafety.
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Fármacos Fotosensibilizantes , Macrófagos Asociados a Tumores , Animales , Ratones , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Macrófagos Asociados a Tumores/efectos de los fármacos , Fototerapia/métodos , Humanos , Ratones Endogámicos BALB C , Luz , Antineoplásicos/química , Antineoplásicos/farmacología , Estructura Molecular , Fotoquimioterapia , Femenino , Tamaño de la Partícula , Células RAW 264.7 , Supervivencia Celular/efectos de los fármacosRESUMEN
To explore the regulatory mechanism of endogenous hormones in the synthesis of anthocyanins in Anoectochilus roxburghii (Wall.) Lindl (A. roxburghii) under different light intensities, this study used metabolomics and transcriptomics techniques to identify the key genes and transcription factors involved in anthocyanin biosynthesis. We also analyzed the changes in and correlations between plant endogenous hormones and anthocyanin metabolites under different light intensities. The results indicate that light intensity significantly affects the levels of anthocyanin glycosides and endogenous hormones in leaves. A total of 38 anthocyanin-related differential metabolites were identified. Under 75% light transmittance (T3 treatment), the leaves exhibited the highest anthocyanin content and differentially expressed genes such as chalcone synthase (CHS), flavonol synthase (FLS), and flavonoid 3'-monooxygenase (F3'H) exhibited the highest expression levels. Additionally, 13 transcription factors were found to have regulatory relationships with 7 enzyme genes, with 11 possessing cis-elements responsive to plant hormones. The expression of six genes and two transcription factors was validated using qRT-PCR, with the results agreeing with those obtained using RNA sequencing. This study revealed that by modulating endogenous hormones and transcription factors, light intensity plays a pivotal role in regulating anthocyanin glycoside synthesis in A. roxburghii leaves. These findings provide insights into the molecular mechanisms underlying light-induced changes in leaf coloration and contribute to our knowledge of plant secondary metabolite regulation caused by environmental factors.
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Antocianinas , Regulación de la Expresión Génica de las Plantas , Luz , Metaboloma , Orchidaceae , Hojas de la Planta , Proteínas de Plantas , Transcriptoma , Antocianinas/biosíntesis , Antocianinas/genética , Antocianinas/metabolismo , Orchidaceae/genética , Orchidaceae/metabolismo , Orchidaceae/efectos de la radiación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Metaboloma/efectos de la radiación , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Reguladores del Crecimiento de las Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/genética , Perfilación de la Expresión Génica/métodos , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
A series of 3-aryl-4-pyrrolyl-maleimides were designed, synthesized, and evaluated for their glycogen synthase kinase-3ß (GSK-3ß) inhibitory activity. Most compounds exhibited potent activity against GSK-3ß. Among them, compounds 11a, 11c, 11h, 11i, and 11j significantly reduced Aß-induced Tau hyperphosphorylation, showing the inhibition of GSK-3ß at the cellular level. Structure-activity relationships were discussed based on the experimental data obtained.
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Inhibidores Enzimáticos/farmacología , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Maleimidas/farmacología , Línea Celular Tumoral , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Glucógeno Sintasa Quinasa 3 beta , Humanos , Maleimidas/síntesis química , Maleimidas/química , Fosforilación/efectos de los fármacos , Relación Estructura-Actividad , Proteínas tau/metabolismoRESUMEN
Background: We describe a patient with sinonasal mucosal melanoma (SNMM) and an inverted papilloma, which existed independently in both nasal cavities. Case presentation: We describe an unusual case of a 74-year-old male patient with SNMM and an inverted papilloma. He presented with symptoms of coughing up blood and pain in the left forehead. The patient underwent surgical resection of the lesion, and the SNMM and inverted papilloma were confirmed by histopathology. The patient refused further treatment after surgery, but was re-admitted 7 months later with local recurrence of the left tumor and systemic metastases. Conclusions: Nasal malignant melanoma with an inverted papilloma in the contralateral nasal cavity is rare and can easily be misdiagnosed as the same tumor by imaging. Simultaneous histopathology of bilateral nasal masses is very necessary. The recommended treatment is surgery for the inverted papilloma. An SNMM is a devastating tumor with poor outcomes.
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Inflammation driven by DNA sensors is now understood to be important to disease pathogenesis. Here, we describe new inhibitors of DNA sensing, primarily of the inflammasome forming sensor AIM2. Biochemistry and molecular modeling has revealed 4-sulfonic calixarenes as potent inhibitors of AIM2 that likely work by binding competitively to the DNA-binding HIN domain. Although less potent, these AIM2 inhibitors also inhibit DNA sensors cGAS and TLR9 demonstrating a broad utility against DNA-driven inflammatory responses. The 4-sulfonic calixarenes inhibited AIM2-dependent post-stroke T cell death, highlighting a proof of concept that the 4-sulfonic calixarenes could be effective at combating post-stroke immunosuppression. By extension, we propose a broad utility against DNA-driven inflammation in disease. Finally, we reveal that the drug suramin, by virtue of its structural similarities, is an inhibitor of DNA-dependent inflammation and propose that suramin could be rapidly repurposed to meet an increasing clinical need.
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[This corrects the article DOI: 10.1093/nsr/nwab232.].
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Background: Pain management, as a key component of enhanced recovery after surgery (ERAS), can effectively relieve perioperative pain and anxiety. However, there are few studies on the application of pain management based on ERAS in pediatric surgery patients. We aimed to examine the effect of ERAS-based perioperative pain management in children with obstructive sleep apnea (OSA) undergoing adenotonsillectomy. Methods: From March 2021 to July 2021, a randomized controlled single-blind study was conducted on children with OSA and scheduled to undergo adenotonsillectomy. The children were randomly assigned to either control group (n = 60) or ERAS group (n = 60). Traditional analgesia measures were provided to children in the control group, whereas ERAS-based optimized analgesia measures were provided to children in the ERAS group. The pain scores, anxiety scores and diet quality scores were compared between the two groups. Results: The pain scores after surgery in the ERAS group were significantly lower than those in the control group at 6 h, 1 day, 3 days, and 5 days after surgery. Furthermore, the diet quality scores in the ERAS group were significantly higher than those in the control group at 6 h, 1 day, 3 days, and 5 days after surgery. The anxiety scores after surgery in the ERAS group were significantly lower than those in the control group. Conclusions: Perioperative pain management based on ERAS can significantly alleviate postoperative pain, improve quality of life, and promote the accelerated rehabilitation of children with OSA undergoing adenotonsillectomy. Level of evidence: 1.
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Potential immune responses resulting from exposure to metal oxide nanoparticles (MeONPs) have been the subject of intensive discussion in the last decade. Despite the extensive use of MeONPs in several applications, their toxic effects on immune cells have rarely been predicted in silico because of the complexity of immune responses and the complicated properties of MeONPs. In the present study, machine learning (ML) methods coupled with high-throughput in vitro bioassays were used to develop models for predicting the toxicity of MeONPs in immune cells. An ML model with a high prediction accuracy (97% and 96% in the training and test sets, respectively) was constructed by resolving the class imbalance problem in training and applying an ensembled algorithm. Further, to verify the model, MeONPs outside the scope of the datasets were selected to examine their cytotoxicity experimentally. The model was validated against independent MeONPs, with an accuracy of 91%. ML methods coupled with intracellular imaging revealed that the toxic ions released in the lysosome were an important determinant of toxicity in immune cells. Furthermore, ζ-potential, electronegativity, and size are crucial factors for predicting nanotoxicity. We believe the established modeling framework will provide useful insights for designing and applying safe nanoparticles and facilitating decision-making for environmental and health protection.