RESUMEN
In Extended Data Fig. 9a of this Article, the bottom micrographs of mPiezo1-ΔL3-4-IRES-GFP and mPiezo1-ΔL7-8-IRES-GFP (labelled 'permeabilized') are inadvertently the same images. The corrected figure panels are shown in the accompanying Amendment.
RESUMEN
The mechanosensitive Piezo channels function as key eukaryotic mechanotransducers. However, their structures and mechanogating mechanisms remain unknown. Here we determine the three-bladed, propeller-like electron cryo-microscopy structure of mouse Piezo1 and functionally reveal its mechanotransduction components. Despite the lack of sequence repetition, we identify nine repetitive units consisting of four transmembrane helices each-which we term transmembrane helical units (THUs)-which assemble into a highly curved blade-like structure. The last transmembrane helix encloses a hydrophobic pore, followed by three intracellular fenestration sites and side portals that contain pore-property-determining residues. The central region forms a 90 Å-long intracellular beam-like structure, which undergoes a lever-like motion to connect THUs to the pore via the interfaces of the C-terminal domain, the anchor-resembling domain and the outer helix. Deleting extracellular loops in the distal THUs or mutating single residues in the beam impairs the mechanical activation of Piezo1. Overall, Piezo1 possesses a unique 38-transmembrane-helix topology and designated mechanotransduction components, which enable a lever-like mechanogating mechanism.
Asunto(s)
Microscopía por Crioelectrón , Activación del Canal Iónico , Canales Iónicos/metabolismo , Canales Iónicos/ultraestructura , Mecanotransducción Celular , Animales , Canales Iónicos/química , Ratones , Modelos Moleculares , Movimiento , Relación Estructura-ActividadRESUMEN
Fabry disease (FD) is a rare X chromosome-linked disorder and can be easily misdiagnosed. Here, we report the case of a 69-year-old male patient with FD who developed heart failure and showed extremely high pulmonary artery pressure. His initial symptom was recurrent atrial fibrillation. The left and right atrial inner diameters were large, and the ventricular wall was thick. Gene analysis which showed GLA c.215T>C p.Met72Thr mutation and single photon emission computed tomography indicated the diagnosis of FD with coronary microvascular dysfunction. The patient was prescribed anti-heart failure drugs, including vericiguat. Following the treatment, his heart function and microvascular perfusion significantly improved, which might be due to the beneficial effects of vericiguat.
Asunto(s)
Enfermedad de Fabry , Compuestos Heterocíclicos con 2 Anillos , Pirimidinas , Humanos , Masculino , Anciano , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/tratamiento farmacológico , Enfermedad de Fabry/diagnóstico , Microcirculación , Electrocardiografía , MutaciónRESUMEN
PURPOSE: To investigate the impact of heterogeneity in patient indications or insemination protocols on neonatal outcomes of singletons following early rescue ICSI (rICSI) treatments. METHODS: A retrospective study was conducted. Propensity score matching and multivariable logistic regression were used to adjust for confounders and biases. RESULTS: A total of 9095 IVF patients, 2063 ICSI patients, and 642 early rICSI patients were included in the study. No differences were detected in neonatal outcomes except small for gestational age (SGA) which increased in early rICSI patients compared with both unmatched and matched IVF groups with the risk ratio (RR) of 1.31 (95% CI: 1.05, 1.64) and 1.49 (95% CI: 1.05, 2.12). Further analysis showed that SGA increased significantly in partial fertilization failure (PFF) cycles with RRs of 1.56 (95% CI: 1.08, 2.27) and 1.78 (95% CI: 1.22, 2.59) compared with both unmatched and matched IVF patients but not in TFF patients. A positive association between fertilization rate via IVF and birth weight z-score was revealed in the PFF patients. CONCLUSION: Early rICSI in patients with total fertilization failure (TFF) appeared to be safe in terms of neonatal outcomes. However, when expanding the indications of rICSI to PFF patients, the SGA in the offspring increased, suggesting a potential effect on long-term health. Since other treatment options, such as using only the IVF-origin embryos still exist for these patients, further studies were needed to confirm the optimal decision for these patients.
Asunto(s)
Enfermedades del Recién Nacido , Inyecciones de Esperma Intracitoplasmáticas , Recién Nacido , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Inyecciones de Esperma Intracitoplasmáticas/efectos adversos , Fertilización In Vitro/efectos adversos , Peso al Nacer , Recién Nacido Pequeño para la Edad Gestacional , Retardo del Crecimiento Fetal/etiología , Enfermedades del Recién Nacido/etiología , Índice de EmbarazoRESUMEN
The health monitoring of CRF (circulation water) pumps is essential for prognostics and management in nuclear power plants. However, the operational status of CRF pumps can vary due to environmental factors and human intervention, and the interrelationships between monitoring parameters are often complex. Consequently, the existing methods face challenges in effectively assessing the health status of CRF pumps. In this study, we propose a health monitoring model for CRF pumps utilizing a meta graph transformer (MGT) observer. Initially, the meta graph transformer, a temporal-spatial graph learning model, is employed to predict trends across the various monitoring parameters of the CRF pump. Subsequently, a fault observer is constructed to generate early warnings of potential faults. The proposed model was validated using real data from CRF pumps in a nuclear power plant. The results demonstrate that the average Mean Absolute Percentage Error (MAPE), Mean Absolute Error (MAE), and Root Mean Square Error (RMSE) of normal predictions were reduced to 1.2385, 0.5614, and 2.6554, respectively. These findings indicate that our model achieves higher prediction accuracy compared to the existing methods and can provide fault warnings at least one week in advance.
RESUMEN
The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration and crescent formation. Although protein markers have revealed the morphological heterogeneity of PECs, the molecular characteristics of PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis of PECs using single-cell RNA sequencing (scRNA-seq) data. Our analysis identified five distinct PEC subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 and PEC-B. Among these subpopulations, PEC- A1 and PEC-A2 were characterized as podocyte progenitors while PEC-A4 represented tubular progenitors. Further dynamic signaling network analysis indicated that activation of PEC-A4 and the proliferation of PEC-A3 played pivotal roles in crescent formation. Analyses suggested that upstream signals released by podocytes, immune cells, endothelial cells and mesangial cells serve as pathogenic signals and may be promising intervention targets in crescentic glomerulonephritis. Pharmacological blockade of two such pathogenic signaling targets, proteins Mif and Csf1r, reduced hyperplasia of the PECs and crescent formation in anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates that scRNA-seq-based analysis provided valuable insights into the pathology and therapeutic strategies for crescentic glomerulonephritis.
Asunto(s)
Glomerulonefritis , Enfermedades Renales , Podocitos , Ratones , Animales , Células Endoteliales/patología , Células Epiteliales/metabolismo , Glomérulos Renales/patología , Podocitos/patología , Glomerulonefritis/patología , Proteínas/metabolismo , Enfermedades Renales/patologíaRESUMEN
AIMS: The aim of this network meta-analysis is to analyze the difference in therapeutic effects between moist dressings and traditional dressings in the treatment of pressure injury (PI), explore the healing, healing time, direct cost, and number of dressing changes of different moist dressings for the management of pressure injuries. BACKGROUND: The incidence of pressure injury is high and the burden of disease is high, but there is no consensus on how to choose moist dressing treatment. DESIGN: A systematic review with network meta-analysis was performed. DATA SOURCES: We searched the Chinese Biomedicine Literature Database and China National Knowledge Infrastructure, Wanfang Database, VIP database, PubMed, Web of Science, EMBASE.com, CENTRAL (Cochrane Central Register of Controlled Trials) and CINAHL to obtain randomized controlled trials (RCTs) on the treatment of PI with moist dressings. REVIEW METHODS: R studio software and Stata 16.0 software were used to compare different moist dressings and traditional dressings. RESULTS: 41 RCTs of moist dressings in the treatment of PI were included. A total of seven kinds of moist dressings, Vaseline gauze and traditional gauze dressing were involved. All RCTs were at a medium to high risk of bias. Overall, moist dressings had more advantages than traditional dressings in terms of various outcome indicators. CONCLUSION: The effect of moist dressings in treating PI is more advantageous than traditional dressings. However, in terms of direct cost and the number of dressings changes, more research is needed to improve the credibility of the network meta-analysis. The results of the network meta-analysis show that the silver ion dressing and alginate dressing are the best choices in the treatment of PI. NO PATIENT OR PUBLIC CONTRIBUTION: This study is a network meta-analysis, which does not require the participation of patients and the public.
Asunto(s)
Úlcera por Presión , Humanos , Úlcera por Presión/terapia , Metaanálisis en Red , Vendajes , Cicatrización de Heridas , Infección de la Herida QuirúrgicaRESUMEN
This study aimed to investigate the effects of renal denervation (RDN) on diabetic cardiomyopathy (DCM) and explore the related mechanisms. Male Sprague-Dawley rats were fed high-fat chow and injected with low-dose streptozotocin to establish a DCM model. Six rats served as controls. The surviving rats were divided into three groups: control group, DCM group and DCM + RDN group. RDN surgery was performed in the fifth week. At the end of the experiment, all rats were subjected to 18F-FDG PET/CT and metabolic cage studies. Cardiac function and structure were evaluated by echocardiography and histology. Myocardial substrate metabolism and mitochondrial function were assessed by multiple methods. In the 13th week, the DCM rats exhibited cardiac hypertrophy and interstitial fibrosis accompanied by diastolic dysfunction. RDN ameliorated DCM-induced cardiac dysfunction (E/A ratio: RDN 1.07 ± 0.18 vs. DCM 0.93 ± 0.12, P < 0.05; E/E' ratio: RDN 10.74 ± 2.48 vs. DCM 13.25 ± 1.99, P < 0.05) and pathological remodeling (collagen volume fraction: RDN 5.05 ± 2.05% vs. DCM 10.62 ± 2.68%, P < 0.05). Abnormal myocardial metabolism in DCM rats was characterized by suppressed glucose metabolism and elevated lipid metabolism. RDN increased myocardial glucose uptake and oxidation while reducing the absorption and utilization of fatty acids. Meanwhile, DCM decreased mitochondrial ATP content, depolarized the membrane potential and inhibited the activity of respiratory chain complexes, but RDN attenuated this mitochondrial damage (ATP: RDN 30.98 ± 7.33 µmol/gprot vs. DCM 22.89 ± 5.90 µmol/gprot, P < 0.05; complexes I, III and IV activity: RDN vs. DCM, P < 0.05). Furthermore, both SGLT2 inhibitor and the combination treatment produced similar effects as RDN alone. Thus, RDN prevented DCM-induced cardiac dysfunction and pathological remodeling, which is related to the improvement of metabolic disorders and mitochondrial dysfunction.
Asunto(s)
Diabetes Mellitus , Cardiomiopatías Diabéticas , Transportador 2 de Sodio-Glucosa/metabolismo , Adenosina Trifosfato , Animales , Desnervación/métodos , Riñón , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Ratas , Ratas Sprague-DawleyRESUMEN
At present, the molecular mechanisms underlying inflammation remain unclear. In recent years, research on inflammation has focused on stimulating cell inflammation by using exogenous pro-inflammatory substances such as lipopolysaccharide (LPS) or inflammatory factors. To investigate the molecular mechanism of inflammation from a new perspective, we designed a nucleic acid nanoflowers (NFs) complex to directly activate inflammatory genes to study the inflammatory response without the need for external microbial factors to trigger an inflammatory response. An RNAa-type target gene-activated NFs was designed. Human umbilical vein endothelial cells (HUVECs) were transfected with NFs carrying small activating RNA (saRNAs) to directly co-activate microRNA (miR)-155 and SHIP1 genes. After RNA activation (RNAa)-type NFs were transferred into HUVECs, the expression of miR-155 and pro-inflammatory and cancer-related factors increased, anti-inflammatory factors were reduced, cell proliferation increased, and cell migration was promoted. IL-1ß protein levels were decreased and SHIP1 expression was downregulated. When miR-155 and its target SHIP1 were both activated, the expression of both was unaltered, maintaining cell homeostasis. This points towards miR-155 overexpression can trigger inflammation, and that miR-155 and its target genes act as a molecular switch role in the development of inflammation.
Asunto(s)
MicroARNs , Ácidos Nucleicos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inflamación/genética , Inflamación/metabolismo , Lipopolisacáridos , MicroARNs/genética , MicroARNs/metabolismo , Ácidos Nucleicos/metabolismoRESUMEN
BACKGROUND: Advanced models including time-lapse imaging and artificial intelligence technologies have been used to predict blastocyst formation. However, the conventional morphological evaluation of embryos is still widely used. The purpose of the present study was to evaluate the predictive power of conventional morphological evaluation regarding blastocyst formation. METHODS: Retrospective evaluation of data from 15,613 patients receiving blastocyst culture from January 2013 through December 2020 in our institution were reviewed. Generalized estimating equations (GEE) were used to establish the morphology-based model. To estimate whether including more features regarding patient characteristics and cycle parameters improve the predicting power, we also establish models including 27 more features with either LASSO regression or XGbosst. The predicted number of blastocyst were associated with the observed number of the blastocyst and were used to predict the blastocyst transfer cancellation either in fresh or frozen cycles. RESULTS: Based on early cleavage and routine observed morphological parameters (cell number, fragmentation, and symmetry), the GEE model predicted blastocyst formation with an AUC of 0.779(95%CI: 0.77-0.787) and an accuracy of 74.7%(95%CI: 73.9%-75.5%) in the validation set. LASSO regression model and XGboost model based on the combination of cycle characteristics and embryo morphology yielded similar predicting power with AUCs of 0.78(95%CI: 0.771-0.789) and 0.754(95%CI: 0.745-0.763), respectively. For per-cycle blastocyst yield, the predicted number of blastocysts using morphological parameters alone strongly correlated with observed blastocyst number (r = 0.897, P < 0.0001) and predicted blastocyst transfer cancel with an AUC of 0.926((95%CI: 0.911-0.94). CONCLUSION: The data suggested that routine morphology observation remained a feasible tool to support an informed decision regarding the day of transfer. However, models based on the combination of cycle characteristics and embryo morphology do not increase the predicting power significantly.
Asunto(s)
Inteligencia Artificial , Implantación del Embrión , Blastocisto , Técnicas de Cultivo de Embriones/métodos , Humanos , Estudios RetrospectivosRESUMEN
Atherosclerosis is generally accepted as a chronic inflammatory disease and is the most important pathological process underlying the cardiovascular diseases. MiR-22 exerts an important role in tumorgenesis, obesity and NAFLD development, as well as cardiovascular diseases. However, a certain role of miR-22 in the pathogenesis of atherosclerosis remains undetermined. Here, we showed that miR-22 exhibited a negative association with the deteriorated atherosclerotic plaque and showed significant downregulated expression in macrophages. Next, treatment of ApoE deficiency (ApoE-/-) mice with miR-22 inhibitors which were then subjected to high fat diet (HFD) for 12 weeks were performed to investigate the function of miR-22 on atherogenesis. The results exhibited that miR-22 inhibition dramatically promoted atherosclerotic plaques but attenuated plaque stabilization which were accompanied by decreased smooth muscle cell and collagen content, but increased macrophage infiltration and lipid accumulation. More importantly, the in vivo and in vitro experiments suggested that miR-22 inhibition accelerated inflammatory response and foam cell formation. Mechanistically, we demonstrated interferon regulator factor 5 (IRF5) was an important target of miR-22 and it was required for the regulation of inflammation mediated by miR-22 inhibition. Collectively, these evidences revealed that miR-22 inhibition promoted the atherosclerosis progression through activation of IRF5.
Asunto(s)
Aterosclerosis/patología , Células Espumosas/inmunología , Regulación de la Expresión Génica , Inflamación/patología , Factores Reguladores del Interferón/metabolismo , MicroARNs/antagonistas & inhibidores , Placa Aterosclerótica/patología , Animales , Apoptosis , Aterosclerosis/etiología , Aterosclerosis/metabolismo , Proliferación Celular , Células Cultivadas , Dieta Alta en Grasa , Inflamación/etiología , Inflamación/metabolismo , Factores Reguladores del Interferón/genética , Ratones , Ratones Noqueados para ApoE , MicroARNs/genética , Placa Aterosclerótica/etiología , Placa Aterosclerótica/metabolismoRESUMEN
Cluster of differentiation 8 (CD8) is a cell surface glycoprotein, which is expressed as 2 forms, αα homodimer or αß heterodimer. Peptide-loaded major histocompatibility complex class I (pMHC-I) molecules are major ligands for both forms of CD8. CD8αß is a coreceptor for the T cell receptor (TCR) and binds to the same cognate pMHC-I as the TCR, thus enabling or augmenting T cell responses. The function of CD8αα homodimers is largely unknown. While CD8αß heterodimer is expressed exclusively on CD8+ T cells, the CD8αα homodimer is present in subsets of T cells and human natural killer (NK) cells. Here, we report that the CD8αα homodimer functions as a coreceptor for KIR3DL1, an inhibitory receptor of NK cells that is specific for certain MHC-I allotypes. CD8αα enhances binding of pMHC-I to KIR3DL1, increases KIR3DL1 clustering at the immunological synapse, and augments KIR3DL1-mediated inhibition of NK cell activation. Additionally, interactions between pMHC-I and CD8αα homodimers regulate KIR3DL1+ NK cell education. Together, these findings reveal another dimension to the modulation of NK cell activity.
Asunto(s)
Antígenos CD8/química , Antígenos CD8/metabolismo , Multimerización de Proteína , Receptores KIR3DL1/metabolismo , Animales , Técnica del Anticuerpo Fluorescente , Antígenos HLA-B/química , Antígenos HLA-B/metabolismo , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Ratones , Modelos Moleculares , Unión Proteica , Conformación Proteica , Receptores KIR3DL1/química , Relación Estructura-ActividadRESUMEN
Galectin-3 is crucial to many physiological and pathological processes. The generally accepted dogma is that galectins function extracellularly by binding specifically to ß(1â4)-galactoside epitopes on cell surface glycoconjugates. Here, we used crystallography and NMR spectroscopy to demonstrate that negatively charged homogalacturonans (HG, linear polysaccharides of α(1â4)-linked-D-galacturonate (GalA)) bind to the galectin-3 carbohydrate recognition domain. The HG carboxylates at the C6 positions in GalA rings mandate that this saccharide bind galectin-3 in an unconventional, "topsy-turvy" orientation that is flipped by about 180o relative to that of the canonical ß-galactoside lactose. In this binding mode, the reducing end GalA ß-anomer of HGs takes the position of the nonreducing end galactose residue in lactose. This novel orientation maintains interactions with the conserved tryptophan and seven of the most crucial lactose-binding residues, albeit with different H-bonding interactions. Nevertheless, the HG molecular orientation and new interactions have essentially the same thermodynamic binding parameters as lactose. Overall, our study provides structural details for a new type of galectin-sugar interaction that broadens glycospace for ligand binding to Gal-3 and suggests how the lectin may recognize other negatively charged polysaccharides like glycoaminoglycans (e.g. heparan sulfate) on the cell surface. This discovery impacts on our understanding of galectin-mediated biological function.
Asunto(s)
Galectina 3/química , Oligosacáridos/química , Cristalografía por Rayos X , Humanos , Espectroscopía de Resonancia Magnética , Modelos MolecularesRESUMEN
The overproduction of proinflammatory cytokines, resulting in what has been described as a cytokine storm or cytokine release syndrome (CRS), may be the key factor in the pathology of severe coronavirus disease 2019 (COVID-19) and is also a crucial cause of death from COVID-19. With the purpose of finding effective and low-toxicity drugs to mitigate CRS, IL-1 blockade agents, which are one of the safest ways to stop this overwhelming innate immune response, are already available in several preliminary reports or are under observational trials and may offer an important treatment option in hyperinflammatory COVID-19. In this review, we described the key information in both case reports and clinical studies on the potential beneficial features of IL-1 inhibitors in COVID-19 patients.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Receptores Tipo I de Interleucina-1/antagonistas & inhibidores , Receptores de Interleucina-1/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/mortalidad , COVID-19/patología , Síndrome de Liberación de Citoquinas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/uso terapéutico , SARS-CoV-2/efectos de los fármacosRESUMEN
BACKGROUND: Health-related quality of life (HRQoL) is an important indicator when evaluating prognosis and disease-related treatments. Our current knowledge of the HRQoL outcomes of unruptured intracranial aneurysm (UIA) patients treated by the endovascular intervention appeared to be very limited. To fill this gap, the present study investigated the HRQoL outcomes and identified the influencing factors in UIA patients treated by endovascular intervention. METHODS: We conducted a single-center cross-sectional study on patients who underwent endovascular treatment for UIAs. HRQoL outcomes were assessed by the 36-item Short Form Health Survey (SF-36). The SF-36 results of the Chinese reference population were used as the reference data. The independent variables with a univariate analysis result of P < 0.05 were included in the multivariate analysis. Finally, multivariable linear regression analysis was performed to identify the factors influencing HRQoL. Bonferroni correction was utilized for multiple testing correction. RESULTS: A total of 200 patients (83 males and 117 females, mean age of 55.2 ± 9.48 years) with UIAs treated by endovascular intervention were enrolled. The scores of SF-36 in 8 domains for UIA patients treated by endovascular intervention did not all reach the average level of the Chinese reference population after an average recovery period of 30.67 ± 8.6 months. Ischemic cerebrovascular disease history, advanced age, and mRS progression at discharge were independent risk factors of HRQoL for UIA patients treated by endovascular intervention, but physical exercise at least once a week and daily sleep time no < 6 h were independent protective factors. CONCLUSION: The HRQoL of UIA patients treated by the endovascular intervention was decreased to varying degrees compared with those of the Chinese reference population. The influencing factors of HRQoL explored by this study provide insights for improving the clinical management and daily lives of these patients. HRQoL assessment should be included in future aneurysm prognostic studies to provide better evidence.
Asunto(s)
Procedimientos Endovasculares , Aneurisma Intracraneal , Estudios Transversales , Femenino , Humanos , Aneurisma Intracraneal/cirugía , Masculino , Persona de Mediana Edad , Calidad de Vida/psicología , Factores de Riesgo , Resultado del TratamientoRESUMEN
Facing the unprecedented global public health crisis caused by coronavirus disease 2019 (COVID-19), nucleic acid tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the gold standard for diagnosing COVID-19. The asymptomatic carriers were not suspected of playing a significant role in the ongoing pandemic, and universal nucleic acid screening in close contacts of confirmed cases and asymptomatic carriers has been carried out in many medium- and high-risk areas for the spread of the virus. Recently, anal swabs for key population screening have been shown to not only reduce missed diagnoses but also facilitate the traceability of infectious sources. As a specimen for the detection of viruses, the goal of this paper is to briefly review the transmission route of SARS-CoV-2 and the necessity of using anal swabs for SARS-CoV-2 screening to minimize transmission and a threat to other people with COVID-19.
Asunto(s)
COVID-19/diagnóstico , Heces/virología , SARS-CoV-2/aislamiento & purificación , COVID-19/transmisión , Prueba de Ácido Nucleico para COVID-19 , Ojo/virología , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Manejo de EspecímenesRESUMEN
Lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions, no effective and curative treatment options are available. Mesenchymal stromal cell (MSC)-based therapy is one of the cutting-edge topics in medical research today. It offers a novel and promising therapeutic option for various acute and chronic lung diseases due to its potent and broad-ranging immunomodulatory activities, bacterial clearance, tissue regeneration, and proangiogenic and antifibrotic properties, which rely on both cell-to-cell contact and paracrine mechanisms. This review covers the sources and therapeutic potential of MSCs. In particular, a total of 110 MSC-based clinical applications, either completed clinical trials with safety and early efficacy results reported or ongoing worldwide clinical trials of pulmonary diseases, are systematically summarized following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, including acute/viral pulmonary disease, community-acquired pneumonia (CAP), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), interstitial lung diseases (ILD), chronic pulmonary fibrosis, bronchiolitis obliterans syndrome (BOS) and lung cancer. The results of recent clinical studies suggest that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, large-scale clinical trials and evaluation of long-term effects are necessary in further studies.
Asunto(s)
Enfermedades Pulmonares/terapia , Trasplante de Células Madre Mesenquimatosas/estadística & datos numéricos , Ensayos Clínicos como Asunto , Humanos , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/tendencias , Resultado del TratamientoRESUMEN
Cytokine release syndrome (CRS) may be the key factor in the pathology of severe coronavirus disease 2019 (COVID-19). As a major driver in triggering CRS in patients with COVID-19, interleukin-6 (IL-6) appears to be a promising target for therapeutics. The results of inhibiting both trans- and classical- signaling with marketed IL-6 inhibitors (tocilizumab, siltuximab and sarilumab) in severe COVID-19 patients are effective based on several small studies and case reports thus far. In this review, we described the evidence of the IL-6 response in patients with COVID-19, clarified the pathogenesis of the role of IL-6-mediated CRS in severe COVID-19, and highlighted the rationale for the use of anti-IL-6 agents and key information regarding the potential features of these IL-6 inhibitors in COVID-19 patients.
Asunto(s)
COVID-19/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/inmunología , Interleucina-6/metabolismo , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , COVID-19/metabolismo , Síndrome de Liberación de Citoquinas/metabolismo , Humanos , Interleucina-6/antagonistas & inhibidores , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND Impaired heart function induced by myocardial infarction is a leading cause of chronic heart failure (HF). This study aimed to investigate the effects and mechanism of noninvasive positive-pressure ventilation (NIPPV) in a rat model of HF due to myocardial infarction. MATERIAL AND METHODS To explore the therapeutic effect and mechanism of NIPPV on acute myocardial infarction-induced HF, we established a rat model of HF by ligating the anterior descending branch of the left coronary artery and confirmed by ultrasonic cardiography and brain natriuretic peptide 45 detection. RESULTS The levels of heat-shock protein (HSP)-70 increased and matrix metalloproteinase (MMP)-2, MMP-9, and tumor necrosis factor (TNF)-alpha decreased in the group that received NIPPV treatment compared with the control group. In addition, the histopathologic results showed less severe inflammatory infiltration and a smaller area of myocardial fibrosis in the NIPPV treatment group. CONCLUSIONS In a rat model of HF due to myocardial infarction, NIPPV resulted in increased levels of HSP70 and reduced expression of MMP2, MMP9, and TNF-alpha and reduced myocardial neutrophil infiltration and fibrosis. Taken together, we showed that NIPPV is an effective treatment for HF induced by myocardial infarction by inhibiting the release of inflammatory factors and preventing microvascular embolism.
Asunto(s)
Insuficiencia Cardíaca/terapia , Infarto del Miocardio/terapia , Respiración con Presión Positiva/métodos , Animales , Cardiomiopatías/patología , Modelos Animales de Enfermedad , Ecocardiografía/métodos , Fibrosis/patología , Proteínas HSP70 de Choque Térmico/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Miocardio/patología , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo , Remodelación Ventricular/efectos de los fármacosRESUMEN
BACKGROUND: Network meta-analysis (NMA) has been widely used in the field of medicine and health, but the research topics and development trends are still unclear. This study aimed to identify the cooperation of countries and institutes and explore the hot topics and future prospects in the field of NMA. METHODS: Data of publications were downloaded from the Web of Science Core Collection. We used CiteSpace V, HistCite 2.1, and Excel 2016 to analyze literature information, including years, journals, countries, institutes, authors, keywords, and co-cited references. RESULTS: NMA research developed gradually before 2010 and rapidly in the following years. 2846 NMA studies were published in 771 journals in six languages. The PLoS One (110, 3.9%) was the most productive journal, and N Engl J Med (5904 co-citations) was the most co-cited journal. The most productive country was the United States (889, 31%) and the most productive institute was the University of Bristol (113, 4.0%). The active collaborations were observed between developed countries and between productive institutes. Of the top 10 authors, four were from the UK, and among the top 10 co-cited authors, six were from the UK. Randomized evidence, oral anti-diabetic drugs, coronary artery bypass, certolizumab pegol, non-valvular atrial fibrillation, and second-line antihyperglycemic therapy were the hot topics in this field. CONCLUSIONS: NMA studies have significantly increased over the past decade, especially from 2015 to 2017. Compared with developing countries, developed countries have contributed more to these publications and have closer cooperation, indicating that cooperation between developed and developing countries should be further strengthened. The treatment of diabetes, cardiovascular diseases, and immune rheumatism are the main hot topics.