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2.
PLoS Pathog ; 19(10): e1011694, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37831643

RESUMO

Alongshan virus (ALSV), a newly discovered member of unclassified Flaviviridae family, is able to infect humans. ALSV has a multi-segmented genome organization and is evolutionarily distant from canonical mono-segmented flaviviruses. The virus-encoded methyltransferase (MTase) plays an important role in viral replication. Here we show that ALSV MTase readily binds S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH) but exhibits significantly lower affinities than canonical flaviviral MTases. Structures of ALSV MTase in the free and SAM/SAH-bound forms reveal that the viral enzyme possesses a unique loop-element lining side-wall of the SAM/SAH-binding pocket. While the equivalent loop in flaviviral MTases half-covers SAM/SAH, contributing multiple hydrogen-bond interactions; the pocket-lining loop of ALSV MTase is of short-length and high-flexibility, devoid of any physical contacts with SAM/SAH. Subsequent mutagenesis data further corroborate such structural difference affecting SAM/SAH-binding. Finally, we also report the structure of ALSV MTase bound with sinefungin, an SAM-analogue MTase inhibitor. These data have delineated the basis for the low-affinity interaction between ALSV MTase and SAM/SAH and should inform on antiviral drug design.


Assuntos
Flavivirus , Metiltransferases , Humanos , Metiltransferases/genética , Flavivirus/genética , Flavivirus/metabolismo , S-Adenosilmetionina/metabolismo , Mutagênese
3.
Sci Rep ; 13(1): 3749, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36878956

RESUMO

Central airway obstruction caused by neck and chest tumors is a very dangerous oncological emergency with high mortality. Unfortunately, there is few literature to discuss an effective way for this life-threating condition. Providing effective airway managements, adequate ventilation and emergency surgical interventions are very important. However, traditional airway managements and respiratory support has only limited effect. In our center, using extracorporeal membrane oxygenation (ECMO) as a novel approach to manage patient with central airway obstruction caused by neck and chest tumors has been adopted. We aimed to show the feasibility: using early ECMO to manage difficult airway, provide oxygenation and support surgical procedure for patients with critical airway stenosis caused by neck and chest tumors. We designed a single-center, small sample size retrospective study based on real-world. We identified 3 patients with central airway obstruction caused by neck and chest tumors. ECMO was used to ensure adequate ventilation to emergency surgery. Control group cannot be established. Because traditional manner very likely led to death of such patients. Details of clinical characteristics, ECMO, surgery and survival outcomes were recorded. Acute dyspnea and cyanosis were the most frequent symptoms. All patients (3/3) showed descending arterial partial pressure of oxygen (PaO2). Computed tomography (CT) revealed severe central airway obstruction caused by neck and chest tumors in all cases (3/3). All patients (3/3) had definite difficult airway. All cases (3/3) received ECMO support and emergency surgical procedure. Venovenous ECMO was the common mode for all cases. 3 patients weaned off ECMO successfully without any ECMO-related complications. Mean duration of ECMO was 3 h (range: 1.5-4.5 h). Under ECMO support, difficult airway management and emergency surgical procedure were finished successfully for all cases (3/3). The mean ICU stay was 3.3 days (range: 1-7 days), and the mean general ward stay was 3.3 days (range: 2-4 days). Pathology demonstrated the tumor dignity for 3 patients including 2 malignant cases and 1 benign case. All patients (3/3) were discharged from hospital successfully. We showed that early ECMO initiation was a safe and feasible approach to manage difficult airway for patients with severe central airway obstruction caused by neck and chest tumors. Meanwhile, early ECMO initiation could ensure security for airway surgical procedure.


Assuntos
Obstrução das Vias Respiratórias , Oxigenação por Membrana Extracorpórea , Humanos , Estudos Retrospectivos , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/cirurgia , Manuseio das Vias Aéreas , Espinhas Dendríticas
5.
Brain Sci ; 12(12)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36552117

RESUMO

Cerebral ischemia impedes the functional or metabolic demands of the central nervous system (CNS), which subsequently leads to irreversible brain damage. While recanalization of blocked vessels recovers cerebral blood flow, it can also aggravate brain injury, termed as ischemia/reperfusion (I/R) injury. Exosomes, nanometric membrane vesicles, attracted wide attention as carriers of biological macromolecules. In the brain, exosomes can be secreted by almost all types of cells, and their contents can be altered during the pathological and clinical processes of cerebral I/R injury. Herein, we will review the current literature on the possible role of cargos derived from exosomes and exosomes-mediated intercellular communication in cerebral I/R injury. The PubMed and Web of Science databases were searched through January 2015. The studies published in English were identified using search terms including "exosomes", "cerebral ischemia-reperfusion injury", "brain ischemia-reperfusion injury", and "stroke". We will also focus on the potential therapeutic effects of stem cell-derived exosomes and underlying mechanisms in cerebral I/R injury. Meanwhile, with the advantages of low immunogenicity and cytotoxicity, high bioavailability, and the capacity to pass through the blood-brain barrier, exosomes also attract more attention as therapeutic modalities for the treatment of cerebral I/R injury.

6.
J Inflamm Res ; 15: 5337-5346, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36131781

RESUMO

Objective: To establish a rapid and concise prognosis scoring system for pancreatitis in the emergency department based on bedside arterial blood gas analysis (ABG). Methods: A single-center, retrospective cohort study was used to establish the new scoring system, and a validation group was used to verify it. The primary endpoint was 60-day death, and secondary endpoints were 28-day death, admission to the intensive care unit (AICU), requirement for mechanical ventilation (MV) and persistent organ failure (POF). Receiver operating characteristic (ROC) curves was drawn to validate the predictive value of the new scoring system. The performance of the new scoring system was compared with that of conventional predictive scoring. Results: 443 patients were in the derivation group and 217 patients in the validation group, of which 27 and 25 died during follow-up. A total of 443 patients in the derivation group, 27 of whom died during the follow-up period. Multivariate regression analysis showed that mental status, hematocrit (HCT), base excess (BE) and Serum ionic calcium (Ca2+) were independent risk factors for 60-day mortality of pancreatitis, and they were used to create a new scoring system (MHBC). In the derivation and validation, the ability of MHBC (AUC= 0.922, 0.773, respectively) to predict 60-day mortality from pancreatitis was no less than that of APACHE II (AUC= 0.838, 0.748, respectively) and BISAP (AUC= 0.791, 0.750, respectively), while, MHBC is more quickly and concisely than APACHE II and BISAP. Compared with MHBC less than or equal to 2, when MHBC is greater than 2, the 28-day mortality, 60-day mortality and the incidence of AICU, MV and POF increased significantly (P <0.001). Conclusion: The MHBC can quickly and concisely evaluate the 60-day mortality, 28-day mortality, and the incidence of AICU, MV and POF of patients with acute pancreatitis in the emergency department.

7.
J Inflamm Res ; 15: 3323-3335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692952

RESUMO

Purpose: The thrombo-inflammatory prognostic score (TIPS) and the bedside index for severity in acute pancreatitis (BISAP) are both scoring systems that enable the rapid prognostic assessment of early-stage acute pancreatitis (AP) patients, but the overall prognostic utility of these individual systems is limited. This study was thus developed to explore whether a combination of TIPS and BISAP scores would offer better insight to facilitate the risk stratification of AP patients. Methods: This single-center retrospective cohort research evaluated AP cases referred to the emergency department from January 1, 2017 to September 30, 2017. The ability of TIPS scores to improve BISAP-based AP patient risk stratification was appraised employing the curves of receiver-operating characteristic (ROC) and decision curve analysis (DCA) approaches. The initial endpoint for this research was 28-day mortality, while secondary endpoints comprised intensive care unit admission (AICU) and mechanical ventilation (MV) over a 28-day follow-up period. Results: Totally, 440 cases enrolled in the current study were divided at a ratio of 1:1 to derivation and validation cohorts. When estimating 28-day mortality, the combination of TIPS and BISAP (T-BISAP) improved the area under the curve (AUC) value in the derivation group from 0.809 to 0.903 (P < 0.05), in addition to similarly improving this AUC value from 0.709 to 0.853 (P < 0.05) in the validation cohort. Moreover, T-BISAP significantly improved the AUC values for 28-day AICU from 0.751 to 0.824 (P < 0.05) and the AUC values for 28-day MV from 0.755 to 0.808 (P < 0.05). A DCA approach revealed T-BISAP to exhibit higher net benefit when used for patient risk stratification as compared to BISAP alone. Conclusion: The addition of TIPS scores to BISAP scores can enable prediction of 28-day adverse clinical outcomes with AP patients in the ED.

8.
J Inflamm Res ; 15: 1227-1235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558187

RESUMO

Purpose: At present, simple, accurate, and efficient prognostic tools for the evaluation of cases with early-stage sepsis in the emergency department (ED) are lacking. An increased blood urea nitrogen to albumin ratio (BAR) has previously been shown to be a valuable biomarker with predictive utility in several diseases. The relationship between BAR and sepsis patient outcomes, however, is not well-understood. This exploration was thus developed for the exploration of the link between BAR values and the short-term prognosis of cases with sepsis. Methods: This was a retrospective cohort research of sepsis cases admitted to the West China Hospital of Sichuan University ED from July 2015 to June 2016. Laboratory data were collected upon ED admission, and 7-day all-cause mortality was the primary study endpoint. Relationships between BAR values and APACE II and SOFA scores were generated assessed with correlation coefficient heatmaps. Independent risk factors were identified through multivariate analyses, with the curves of receiver operating characteristic (ROC) being employed to gauge the value of BAR as a predictor of the risk of mortality in sepsis cases. Results: In sum, 801 patients participated in the present investigation. BAR values were strongly correlated with APACHE II and SOFA scores. In a multivariate logistic regression assessment, BAR was identified as an independent predictor of mortality among patients with sepsis (HR=1.032, 95% CI: 1.010-1.055, P=0.004). BAR exhibited an AUC of 0.741 (95% CI: 0.688-0.793, P<0.001) when used to predict patient mortality risk, with 5.27 being the optimal BAR cut-off. Conclusion: We found that BAR can be used as a reliable biomarker to predict mortality in patients with sepsis.

9.
Front Med (Lausanne) ; 9: 847089, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372375

RESUMO

Loss of gray-white matter discrimination is the primary early imaging finding within of cranial computed tomography in cardiac arrest survivors, and this has been also regarded as a novel predictor for evaluating neurologic outcome. As displayed clearly on computed tomography and based on sensitivity to hypoxia, the gray-white matter ratio at basal ganglia (GWR-BG) region was frequently detected to assess the neurologic outcome by several studies. The specificity of GWR-BG is 72.4 to 100%, while the sensitivity is significantly different. Herein we review the mechanisms mediating cerebral edema following cardiac arrest, demonstrate the determination procedures with respect to GWR-BG, summarize the related researches regarding GWR-BG in predicting neurologic outcomes within cardiac arrest survivors, and discuss factors associated with predicting the accuracy of this methodology. Finally, we describe the effective measurements to increase the sensitivity of GWR-BG in predicting neurologic outcome.

10.
Am J Emerg Med ; 53: 190-195, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35063891

RESUMO

BACKGROUND: Illness severity of patients with acute pancreatitis (AP) at early stage is crucial because the identified moderate and severe cases need early intensive care to reduce the risk of serious complications such as multi-organ failure. Although red blood cell distribution width(RDW)and serum calcium(Ca)alone can be used as predictors of the severity of AP, they have low sensitivity and specificity. Thus, this study is aimed at evaluating the value of the ratio of RDW to serum calcium, which can all be acquired on admission, in predicting the severity of AP. METHODS: This study was based on a retrospective cohort study on patients with AP at the emergency department (ED) of West China Hospital Hospital from January 2016 to June 2016. We divided the patients with AP into two groups, mild acute pancreatitis (MAP) and moderate severe acute pancreatitis (MSAP) + severe acute pancreatitis (SAP). A receiver-operating characteristic (ROC) curve analysis was used to valuate the predictive value of the ratio of RDW to serum calcium for the severity of AP patients and the cut-off value for the ratio of RDW to serum calcium was calculated with sensitivity and specificity. P < 0.05 was considered statistically significant. RESULTS: A total of 666 AP patients were enrolled in this study. These patients were divided into MAP (n = 518) and MSAP+SAP (n = 148) groups. The AUC of RDW/ Ca was 0.912 (95% CI 0.887 to 0.937, P < 0.001), larger than the AUCs of RDW (AUC = 0.768, 95% CI 0.723 to 0.812, P < 0.001) and Ca (AUC = 0.875, 95% CI 0.844 to 0.906, P < 0.001). The optimal cut-off value for RDW/ Ca to predict MSAP and SAP was 7.04 (sensitivity = 0.885, specificity = 0.834). CONCLUSION: The RDW/Ca might be a valuable predictor of the severity of patients with AP.


Assuntos
Cálcio , Pancreatite , Doença Aguda , Biomarcadores , Eritrócitos , Humanos , Pancreatite/diagnóstico , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
11.
J Inflamm Res ; 15: 395-408, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35068938

RESUMO

BACKGROUND: Acute pancreatitis (AP) is a multifactorial disease that is associated with substantial morbidity and mortality. Thrombosis and inflammation are involved in the development and progression of AP. AIM: To develop and validate a novel and simple scoring system for predicting 28-day adverse outcomes in AP patients based on a thrombotic and an inflammatory biomarker. METHODS: A single-center, retrospective cohort study was used to establish the new scoring system (thrombo-inflammatory prognostic score; TIPS), and another study was used to verify it. The study end points were 28-day mortality, requirement for mechanical ventilation (MV), persistent organ failure (POF), and admission to the intensive care unit (AICU). Receiver operating characteristic (ROC) curves was drawn to validate the predictive value of the TIPS. The performance of the TIPS was compared with that of conventional predictive scoring systems. Logistic regression models were used to investigate the relationship between the TIPS and the different end points. RESULTS: Among 440 patients with AP in the derivation group, 27 patients died within the 28-day follow-up period. Prothrombin time (PT) and interleukin-6 (IL-6) were used to calculate the TIPS. The TIPS (AUC=0.843) showed a performance comparable to that of the more established APACHE II (AUC=0.841), SOFA (AUC=0.797), BISAP (AUC=0.762), and Balthazar CT (AUC=0.655) in predicting 28-day mortality in AP. The 28-day mortality and the incidence of MV, POF, and AICU were significantly higher among patients with a higher TIPS (P<0.001). The results of logistic regression analyses indicated that the TIPS was independently associated with the risks of 28-day mortality, AICU, MV and POF. CONCLUSION: The TIPS can enable prediction of 28-day adverse clinical outcomes with AP patients in the ED.

12.
Disaster Med Public Health Prep ; 16(1): 29-32, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-32958087

RESUMO

OBJECTIVE: In this study, we aimed to evaluate the correlation between the trauma score of individuals wounded in the Lushan earthquake and emergency workload for treatment. We further created a trauma score-emergency workload calculation model. METHODS: We included data from patients wounded in the Lushan earthquake and treated at West China Hospital, Sichuan University. We calculated scores per the following models separately: Revised Trauma Score (RTS), Prehospital Index (PHI), Circulation Respiration Abdominal Movement Speech (CRAMS), Therapeutic Intervention Scoring System (TISS-28), and Nursing Activities Score (NAS). We assessed the association between values for CRAMS, PHI, and RTS and those for TISS-28 and NAS. Subsequently, we built a trauma score-emergency workload calculation model to quantitative workload estimation. RESULTS: Significant correlations were observed for all pairs of trauma scoring models with emergency workload scoring models. TISS-28 score was significantly associated with PHI score and RTS; however, no significant correlation was observed between the TISS-28 score and CRAMS score. CONCLUSIONS: CRAMS, PHI, and RTS were consistent in evaluating the injury condition of wounded individuals; TISS-28 and NAS scores were consistent in evaluating the required treatment workload. Dynamic changes in emergency workload in unit time were closely associated with wounded patient visits.


Assuntos
Terremotos , China , Correlação de Dados , Serviço Hospitalar de Emergência , Humanos , Carga de Trabalho
13.
Circ Res ; 130(1): 48-66, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34763521

RESUMO

BACKGROUND: Patients with acute myocardial infarction suffer systemic metabolic dysfunction via incompletely understood mechanisms. Adipocytes play critical role in metabolic homeostasis. The impact of acute myocardial infarction upon adipocyte function is unclear. Small extracellular vesicles (sEVs) critically contribute to organ-organ communication. Whether and how small extracellular vesicle mediate post-MI cardiomyocyte/adipocyte communication remain unknown. METHODS: Plasma sEVs were isolated from sham control (Pla-sEVSham) or 3 hours after myocardial ischemia/reperfusion (Pla-sEVMI/R) and incubated with adipocytes for 24 hours. Compared with Pla-sEVSham, Pla-sEVMI/R significantly altered expression of genes known to be important in adipocyte function, including a well-known metabolic regulatory/cardioprotective adipokine, APN (adiponectin). Pla-sEVMI/R activated 2 (PERK-CHOP and ATF6 [transcription factor 6]-EDEM [ER degradation enhancing alpha-mannosidase like protein 1] pathways) of the 3 endoplasmic reticulum (ER) stress pathways in adipocytes. These pathological alterations were also observed in adipocytes treated with sEVs isolated from adult cardiomyocytes subjected to in vivo myocardial ischemia/reperfusion (MI/R) (Myo-sEVMI/R). Bioinformatic/RT-qPCR analysis demonstrates that the members of miR-23-27-24 cluster are significantly increased in Pla-sEVMI/R, Myo-sEVMI/R, and adipose tissue of MI/R animals. Administration of cardiomyocyte-specific miR-23-27-24 sponges abolished adipocyte miR-23-27-24 elevation in MI/R animals, supporting the cardiomyocyte origin of adipocyte miR-23-27-24 cluster. In similar fashion to Myo-sEVMI/R, a miR-27a mimic activated PERK-CHOP and ATF6-EDEM-mediated ER stress. Conversely, a miR-27a inhibitor significantly attenuated Myo-sEVMI/R-induced ER stress and restored APN production. RESULTS: An unbiased approach identified EDEM3 (ER degradation enhancing alpha-mannosidase like protein 3) as a novel downstream target of miR-27a. Adipocyte EDEM3 deficiency phenocopied multiple pathological alterations caused by Myo-sEVMI/R, whereas EDEM3 overexpression attenuated Myo-sEVMI/R-resulted ER stress. Finally, administration of GW4869 or cardiomyocyte-specific miR-23-27-24 cluster sponges attenuated adipocyte ER stress, improved adipocyte endocrine function, and restored plasma APN levels in MI/R animals. CONCLUSIONS: We demonstrate for the first time that MI/R causes significant adipocyte ER stress and endocrine dysfunction by releasing miR-23-27-24 cluster-enriched small extracellular vesicle. Targeting small extracellular vesicle-mediated cardiomyocyte-adipocyte pathological communication may be of therapeutic potential to prevent metabolic dysfunction after MI/R.


Assuntos
Adipócitos/metabolismo , Comunicação Celular , Estresse do Retículo Endoplasmático , Vesículas Extracelulares/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Adiponectina/metabolismo , Animais , Masculino , Proteínas de Membrana/metabolismo , Camundongos , MicroRNAs/metabolismo , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo
14.
Int Immunopharmacol ; 102: 108395, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34915410

RESUMO

Septic acute kidney injury (AKI) always accounts for high mortality of septic patients in ICU. Due to its not well understood mechanism for infection and immune-regulation in kidney dysfunction, there is a lack of effective therapy without side effects. Dimethyl fumarate (DMF) as an immunomodulatory molecule has been approved for treatment to multiple sclerosis. However, the therapeutic effect and immunomodulatory role underlying DMF action in septic AKI is unclear. This study aimed to elucidate the role of DMF in lipopolysaccharide (LPS)-induced septic AKI involving macrophage regulation. In current study, we administered DMF by oral gavage to mice with LPS-induced AKI, then harvested serum and kidney at three different time points. We further isolated Bone marrow-derived macrophages (BMDMs) from mice and stimulated them with LPS followed by DMF treatment. To explore immunomodulatory role of DMF in macrophages, we depleted macrophages in mice using liposomal clodronate after DMF treatment upon LPS-induced septic AKI. Then we observed that DMF attenuated renal dysfunction and murine pathological kidney injury after LPS injection. DMF could inhibit translocation of phosphorylated NF-κB p65 and suppress macrophage activation in LPS-induced AKI. DMF reduced the secretion of TNF-α and IL-6 whereas increased the secretion of IL-10 and Arg-1 in BMDMs after LPS stimulation. DMF also inhibited NF-κB p65 phosphorylation in BMDMs after LPS stimulation. Importantly, the effect of DMF against LPS-induced AKI, macrophage activation, and translocation of phosphorylated NF-κB p65 was impaired upon macrophage depletion. Thus, DMF could attenuate LPS-induced septic AKI by suppression of NF-κB p65 phosphorylation and macrophage activation. This work suggested the potential therapeutic role of DMF for patients in ICU threatened by septic AKI.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Glutamatos/uso terapêutico , Ativação de Macrófagos/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Fosforilação
15.
Gastroenterol Res Pract ; 2021: 6699421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354747

RESUMO

INTRODUCTION: Acute pancreatitis (AP) is a sudden inflammatory process in the pancreas with variable involvement of nearby organs or other organ systems, and it is a common cause for hospitalization of gastrointestinal origin. Early prediction of the prognosis of patients with AP is important to help physicians triage the patients and decrease mortality. Red cell distribution width (RDW) and total serum calcium (TSC) have been reported to be useful predictors of the severity of AP, but if these parameters are associated with the prognosis of AP is unknown. The objective of the study was to evaluate whether RDW/TSC can be used to predict the prognosis of patients with AP at an early stage. METHODS: We retrospectively enrolled AP patients admitted to the emergency department of West China Hospital of Sichuan University from January 1, 2016, to June 30, 2016. According to the prognosis, AP patients were divided into ICU group and non-ICU group, surgery group and nonsurgery group, and hospital survival group and hospital death group. Demographic information and clinical and laboratory parameters of all enrolled patients after being admitted to ED were compared between the groups. The receiver operator characteristic (ROC) curves were used to evaluate the prognostic values of RDW, TSC, and RDW/TSC in patients with AP. RESULTS: A total of 666 AP patients were enrolled in this study, with an average age of 47.99 ± 14.11 years, including 633 patients who survived to discharge and 33 patients who died during hospitalization. The areas under the curve (AUC) of RDW and RDW/TSC predict that patients need to be admitted to ICU (0.773 vs. 0.824 vs. 0.723), patients need surgery treatment (0.744 vs. 0.768 vs. 0.690), and patients survived to hospital discharge (0.809 vs. 0.855 vs. 0.780) were greater than that of TSC, with RDW/TSC being the greatest. CONCLUSIONS: RDW/TSC may be a new method to identify the AP patients who need to be transferred to the ICU, accompanying complications which need surgery treatment, or may be died in hospital at an early stage, and we should pay more attention to RDW/TSC in patients with AP, for they may have a worse prognosis.

17.
Signal Transduct Target Ther ; 6(1): 223, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112762

RESUMO

CD38 is the main enzyme for nicotinamide adenine dinucleotide (NAD) degradation in mammalian cells. Decreased NAD levels are closely related to metabolic syndromes and aging-related diseases. Our study showed that CD38 deficiency significantly alleviated angiotensin II (Ang II)-induced vascular remodeling in mice, as shown by decreased blood pressures; reduced vascular media thickness, media-to-lumen ratio, and collagen deposition; and restored elastin expression. However, our bone marrow transplantation assay showed that CD38 deficiency in lymphocytes led to lack of protection against Ang II-induced vascular remodeling, suggesting that the effects of CD38 on Ang II-induced vascular remodeling might rely primarily on vascular smooth muscle cells (VSMCs), not lymphocytes. In addition, we observed that CD38 deficiency or NAD supplementation remarkably mitigated Ang II-induced vascular senescence by suppressing the biogenesis, secretion, and internalization of senescence-associated small extracellular vesicles (SA-sEVs), which facilitated the senescence of neighboring non-damaged VSMCs. Furthermore, we found that the protective effects of CD38 deficiency on VSMC senescence were related to restoration of lysosome dysfunction, particularly with respect to the maintenance of sirtuin-mediated mitochondrial homeostasis and activation of the mitochondria-lysosomal axis in VSMCs. In conclusion, our findings demonstrated that CD38 and its associated intracellular NAD decline are critical for Ang II-induced VSMC senescence and vascular remodeling.


Assuntos
ADP-Ribosil Ciclase 1/genética , Senescência Celular/genética , Hipertensão/genética , Glicoproteínas de Membrana/genética , Remodelação Vascular/genética , ADP-Ribosil Ciclase 1/antagonistas & inibidores , Angiotensina II/farmacologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Vesículas Extracelulares/efeitos dos fármacos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/patologia , Glicoproteínas de Membrana/antagonistas & inibidores , Camundongos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos
18.
Adv Mater ; 33(14): e2006302, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33656775

RESUMO

Room-temperature-high-efficiency light-emitting diodes based on metal halide perovskite FAPbI3 are shown to be able to work perfectly at low temperatures. A peak external quantum efficiency (EQE) of 32.8%, corresponding to an internal quantum efficiency of 100%, is achieved at 45 K. Importantly, the devices show almost no degradation after working at a constant current density of 200 mA m-2 for 330 h. The enhanced EQEs at low temperatures result from the increased photoluminescence quantum efficiencies of the perovskite, which is caused by the increased radiative recombination rate. Spectroscopic and calculation results suggest that the phase transitions of the FAPbI3 play an important role for the enhancement of exciton binding energy, which increases the recombination rate.

20.
Light Sci Appl ; 9: 89, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509296

RESUMO

Light-emitting diodes (LEDs) based on perovskites show great potential in lighting and display applications. However, although perovskite films with high photoluminescence quantum efficiencies are commonly achieved, the efficiencies of perovskite LEDs are largely limited by the low light out-coupling efficiency. Here, we show that high-efficiency perovskite LEDs with a high external quantum efficiency of 20.2% and an ultrahigh radiant exitance up to 114.9 mW cm-2 can be achieved by employing the microcavity effect to enhance light extraction. The enhanced microcavity effect and light out-coupling efficiency are confirmed by the study of angle-dependent emission profiles. Our results show that both the optical and electrical properties of the device need to be optimized to achieve high-performance perovskite LEDs.

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