RESUMEN
Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated T cells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.
Asunto(s)
Tolerancia Inmunológica , Péptidos y Proteínas de Señalización Intercelular , Macrófagos , FN-kappa B , Sepsis , Factores de Transcripción , Animales , Ratones , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Macrófagos/inmunología , FN-kappa B/metabolismo , Sepsis/inmunología , Sepsis/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factores de Transcripción/metabolismo , Huésped InmunocomprometidoRESUMEN
BACKGROUND: Given increases in China's aging population, the growing demand for public health services and the shortage of human resources among nurses have become more prominent. Under such a background, "Internet + Nursing Services" have received more attention. Thus, exploring the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and utilizing internet technology to increase the supply of nursing services has become a key issue. OBJECTIVE: This study aimed to develop a scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" and to test the validity and reliability of the scale. METHODS: A preliminary scale was developed based on a literature review, theoretical research, semistructured qualitative interviews, and two rounds of Delphi expert inquiry. A convenient sampling method was used for the questionnaire survey. A 5-point Likert scale was used to evaluate the importance of the items. The survey data of 659 clinical nurses obtained from February to March 2023 were used for item analysis, exploratory factor analysis (EFA), and reliability and validity tests of the scale. The survey data of 538 clinical nurses obtained in April 2023 were used for confirmatory factor analysis (CFA) of the final scale. RESULTS: The final scale consists of 25 items and 4 dimensions (performance expectations, perceived risk, need for professional knowledge training, and nonprofessional knowledge training). The scale showed good structural validity and content validity: the Cronbach's α coefficient of the scale was 0.955, the split-half reliability was 0.778, the test-retest reliability was 0.944, the kaiser-meyer-olkin(KMO) value was 0.960, and the cumulative variance contribution rate of the 4 common factors was 83.147%. The scale content validity index(S-CVI) was 0.914. The confirmatory factor analysis model had favorable fit indices: χ2/df = 4.234, RMSEA = 0.078, NFI = 0.940, IFI = 0.953, TLI = 0.947, and CFI = 0.953. CONCLUSION: The scale for assessing the barriers to and facilitators of nurses' willingness to participate in "Internet + Nursing Services" has good reliability and validity, and provides a reference for evaluating nurses' willingness to participate in "Internet + Nursing Services".
RESUMEN
BACKGROUND: Influenza B virus induced myocarditis is a rare complication with potentially wide variations in severity and clinical presentation, and the pathogenesis is unclear. CASE PRESENTATION: We describe a rare case of a 7-year-old boy who developed fulminant myocarditis (FM) due to influenza B virus infection. Treatment measures included mechanical ventilation, vasoactive agents, Extracorporeal membrane oxygenation (ECMO), Continuous Renal Replacement Therapy (CRRT), anti-inflammatory, antiviral, anti-infection, and enteral nutrition support. After 10 days of treatment, the patient succumbed to multiorgan failure. CONCLUSIONS: After a systematic review of the literature, we found that this disease predominantly affects females, with pediatric cases exceedingly rare. Fulminant myocarditis (FM) progresses rapidly, poses significant treatment challenges sporadic, and carries a poor prognosis. Interestingly, literature reports suggest that anti-thymocyte globulin therapy may have a positive impact in treating FM, potentially offering new insights into its pathogenesis and clinical management.
Asunto(s)
Virus de la Influenza B , Gripe Humana , Miocarditis , Niño , Humanos , Masculino , Oxigenación por Membrana Extracorpórea , Resultado Fatal , Gripe Humana/complicaciones , Gripe Humana/virología , Miocarditis/virología , Miocarditis/etiologíaRESUMEN
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Most patients with sepsis underwent a state of immune suppression after surviving the acute inflammatory response, and were susceptible to secondary nosocomial infections, leading to a prolonged hospitalization and increased mortality rate. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population with immunosuppressive activities, can contribute to the development of immunosuppression in patients with cancer and inhibit the host immune response, but the characteristics of MDSCs and their functional mechanism has not been fully addressed in the development of sepsis-induced immunosuppression. Thus, this review will summary the new findings on the mechanisms of MDSCs in septic immunosuppressionin order to provide ideas and directions for targeting MDSCs as treatment of septic immunosuppression.
Asunto(s)
Infección Hospitalaria , Células Supresoras de Origen Mieloide , Sepsis , Humanos , Terapia de Inmunosupresión , InflamaciónRESUMEN
COVID-19 is an acute, complex disorder that was caused by a new ß-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on current reports, it was surprising that the characteristics of many patients with COVID-19, who fulfil the Berlin criteria for acute respiratory distress syndrome (ARDS), are not always like those of patients with typical ARDS and can change over time. While the mechanisms of COVID-19-related respiratory dysfunction in COVID-19 have not yet been fully elucidated, pulmonary microvascular thrombosis is speculated to be involved. Considering that thrombosis is highly related to other inflammatory lung diseases, immunothrombosis, a two-way process that links coagulation and inflammation, seems to be involved in the pathophysiology of COVID-19, including respiratory dysfunction. Thus, the current manuscript will describe the proinflammatory milieu in COVID-19, summarize current evidence of thrombosis in COVID-19, and discuss possible interactions between these two.
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COVID-19/inmunología , COVID-19/patología , Inflamación/virología , Síndrome de Dificultad Respiratoria/virología , Trombosis/virología , Humanos , Inflamación/inmunología , Inflamación/patología , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/patología , SARS-CoV-2 , Trombosis/inmunología , Trombosis/patologíaRESUMEN
Mechanotransduction couples mechanical stimulation with ion flux, which is critical for normal biological processes involved in neuronal cell development, pain sensation, and red blood cell volume regulation. Although they are key mechanotransducers, mechanosensitive ion channels in mammals have remained difficult to identify. In 2010, Coste and colleagues revealed a novel family of mechanically activated cation channels in eukaryotes, consisting of Piezo1 and Piezo2 channels. These have been proposed as the long-sought-after mechanosensitive cation channels in mammals. Piezo1 and Piezo2 exhibit a unique propeller-shaped architecture and have been implicated in mechanotransduction in various critical processes, including touch sensation, balance, and cardiovascular regulation. Furthermore, several mutations in Piezo channels have been shown to cause multiple hereditary human disorders, such as autosomal recessive congenital lymphatic dysplasia. Notably, mutations that cause dehydrated hereditary xerocytosis alter the rate of Piezo channel inactivation, indicating the critical role of their kinetics in normal physiology. Given the importance of Piezo channels in understanding the mechanotransduction process, this review focuses on their structural details, kinetic properties and potential function as mechanosensors. We also briefly review the hereditary diseases caused by mutations in Piezo genes, which is key for understanding the function of these proteins.
RESUMEN
Sepsis is a clinical syndrome that resulting from a dysregulated inflammatory response to infection that leads to organ dysfunction. The dysregulated inflammatory response transitions from a hyper-inflammatory phase to a hypo-inflammatory or immunosuppressive phase. Currently, no phase-specific molecular-based therapies are available for monitoring the complex immune response and treating sepsis due to individual variations in the timing and overlap of the dysregulated immune response in most patients. Glucocorticoid-induced leucine zipper (GILZ), is broadly present in multiple tissues and circumvent glucocorticoid resistance (GCR) or unwanted side effects. Recently, the characteristics of GILZ downregulation during acute hyperinflammation and GILZ upregulation during the immunosuppressive phase in various inflammatory diseases have been well documented, and the protective effects of GILZ have gained attention in the field of sepsis. However, whether GILZ could be a promising candidate biomarker for monitoring and treating septic patients remains unknown. Here, we discuss the effect of GILZ in sepsis and sepsis-induced immunosuppression.