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1.
BMC Pulm Med ; 24(1): 128, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481171

RESUMO

BACKGROUND: With the increasing research on extracellular vesicles (EVs), EVs have received widespread attention as biodiagnostic markers and therapeutic agents for a variety of diseases. Stem cell-derived EVs have also been recognized as a new viable therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). To assess their efficacy, we conducted a meta-analysis of existing preclinical experimental animal models of EVs for ALI treatment. METHODS: The database was systematically interrogated for pertinent data encompassing the period from January 2010 to April 2022 concerning interventions involving extracellular vesicles (EVs) in animal models of acute lung injury (ALI). The lung injury score was selected as the primary outcome measure for statistical analysis. Meta-analyses were executed utilizing RevMan 5.3 and State15.1 software tools. RESULTS: The meta-analyses comprised 31 studies, exclusively involving animal models of acute lung injury (ALI), categorized into two cohorts based on the presence or absence of extracellular vesicle (EV) intervention. The statistical outcomes from these two study groups revealed a significant reduction in lung injury scores with the administration of stem and progenitor cell-derived EVs (SMD = -3.63, 95% CI [-4.97, -2.30], P < 0.05). Conversely, non-stem cell-derived EVs were associated with an elevation in lung injury scores (SMD = -4.34, 95% CI [3.04, 5.63], P < 0.05). EVs originating from stem and progenitor cells demonstrated mitigating effects on alveolar neutrophil infiltration, white blood cell counts, total cell counts in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight ratios (W/D), and total protein in BALF. Furthermore, pro-inflammatory mediators exhibited down-regulation, while anti-inflammatory mediators demonstrated up-regulation. Conversely, non-stem cell-derived EVs exacerbated lung injury. CONCLUSION: In preclinical animal models of acute lung injury (ALI), the administration of extracellular vesicles (EVs) originating from stem and progenitor cells demonstrably enhances pulmonary function. This ameliorative effect is attributed to the mitigation of pulmonary vascular permeability and the modulation of immune homeostasis, collectively impeding the progression of inflammation. In stark contrast, the utilization of EVs derived from non-stem progenitor cells exacerbates the extent of lung injury. These findings substantiate the potential utility of EVs as a novel therapeutic avenue for addressing acute lung injury.


Assuntos
Lesão Pulmonar Aguda , Vesículas Extracelulares , Animais , Humanos , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/metabolismo , Pulmão , Inflamação/metabolismo , Líquido da Lavagem Broncoalveolar , Vesículas Extracelulares/metabolismo , Modelos Animais de Doenças
2.
Brain Topogr ; 37(3): 388-396, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-36892651

RESUMO

Previous research revealed various aspects of resting-state EEG for depression and insomnia. However, the EEG characteristics of depressed subjects with insomnia are rarely studied, especially EEG microstates that capture the dynamic activities of the large-scale brain network. To fill these research gaps, the present study collected resting-state EEG data from 32 subclinical depression subjects with insomnia (SDI), 31 subclinical depression subjects without insomnia (SD), and 32 healthy controls (HCs). Four topographic maps were generated from clean EEG data after clustering and rearrangement. Temporal characteristics were obtained for statistical analysis, including cross-group variance analysis (ANOVA) and intra-group correlation analysis. In our study, the global clustering of all individuals in the EEG microstate analysis revealed the four previously discovered categories of microstates (A, B, C, and D). The occurrence of microstate B was lower in SDI than in SD and HC subjects. The correlation analysis showed that the total Pittsburgh Sleep Quality Index (PSQI) score negatively correlated with the occurrence of microstate C in SDI (r = - 0.415, p < 0.05). Conversely, there was a positive correlation between Self-rating Depression Scale (SDS) scores and the duration of microstate C in SD (r = 0.359, p < 0.05). These results indicate that microstates reflect altered large-scale brain network dynamics in subclinical populations. Abnormalities in the visual network corresponding to microstate B are an electrophysiological characteristic of subclinical individuals with symptoms of depressive insomnia. Further investigation is needed for microstate changes related to high arousal and emotional problems in people suffering from depression and insomnia.


Assuntos
Mapeamento Encefálico , Distúrbios do Início e da Manutenção do Sono , Humanos , Mapeamento Encefálico/métodos , Depressão , Eletroencefalografia , Encéfalo/fisiologia
3.
J Transl Med ; 21(1): 881, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057857

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has impacted approximately 390 million people worldwide and the morbidity is increasing every year. However, due to the poor treatment efficacy of COPD, exploring novel treatment has become the hotpot of study on COPD. Endothelial progenitor cells (EPCs) aging is a possible molecular way for COPD development. We aimed to explore the effector whether intravenous administration of EPCs has therapeutic effects in COPD mice. METHODS: COPD mice model was induced by cigarette smoke exposure and EPCs were injected intravenously to investigate their effects on COPD mice. At day 127, heart, liver, spleen, lung and kidney tissues of mice were harvested. The histological effects of EPCs intervention on multiple organs of COPD mice were detected by morphology assay. Quantitative real-time PCR and Western blotting were used to detect the effect of EPCs intervention on the expression of multi-organ senescence-related indicators. And we explored the effect of EPCs systematically intervening on senescence-related USP7/p300 pathway. RESULTS: Compared with COPD group, senescence-associated ß-galactosidase activity was decreased, protein and mRNA expression of p16 was down-regulated, while protein and mRNA expression of cyclin D1 and TERT were up-regulated of multiple organs, including lung, heart, liver, spleen and kidney in COPD mice after EPCs system intervention. But the morphological alterations of the tissues described above in COPD mice failed to be reversed. Mechanistically, EPCs systemic administration inhibited the expression of mRNA and protein of USP7 and p300 in multiple organs of COPD mice, exerting therapeutic effects. CONCLUSIONS: EPCs administration significantly inhibited the senescence of multiple organs in COPD mice via down-regulating USP7/p300 pathway, which presents a possibility of EPCs therapy for COPD.


Assuntos
Células Progenitoras Endoteliais , Doença Pulmonar Obstrutiva Crônica , Transdução de Sinais , Animais , Humanos , Camundongos , Senescência Celular , Células Progenitoras Endoteliais/patologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Mensageiro/metabolismo , Peptidase 7 Específica de Ubiquitina/metabolismo , Regulação para Baixo
4.
Front Immunol ; 14: 1203687, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022612

RESUMO

Sepsis is a hyper-heterogeneous syndrome in which the systemic inflammatory response persists throughout the course of the disease and the inflammatory and immune responses are dynamically altered at different pathogenic stages. Gasdermins (GSDMs) proteins are pore-forming executors in the membrane, subsequently mediating the release of pro-inflammatory mediators and inflammatory cell death. With the increasing research on GSDMs proteins and sepsis, it is believed that GSDMs protein are one of the most promising therapeutic targets in sepsis in the future. A more comprehensive and in-depth understanding of the functions of GSDMs proteins in sepsis is important to alleviate the multi-organ dysfunction and reduce sepsis-induced mortality. In this review, we focus on the function of GSDMs proteins, the molecular mechanism of GSDMs involved in sepsis, and the regulatory mechanism of GSDMs-mediated signaling pathways, aiming to provide novel ideas and therapeutic strategies for the diagnosis and treatment of sepsis.


Assuntos
Gasderminas , Sepse , Humanos , Morte Celular , Mediadores da Inflamação , Síndrome
5.
Tob Induc Dis ; 21: 122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37794858

RESUMO

INTRODUCTION: Endothelial progenitor cells (EPCs) are the main source of endothelial cells. The senescence of EPCs is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke extract (CSE) can directly induce the dysfunction and increased expression of senescence-related markers in EPCs cultured in vitro. Histone acetyltransferase p300 is a transcriptional activator, and its changes can lead to cell senescence. The present study investigated whether CSE can induce the senescence of EPCs by upregulating p300. METHODS: EPCs were isolated from bone marrow of C57BL/6J mice by density gradient centrifugation. The p300 inhibitor C646 and agonist CTPB were used to interfere with EPCs, cell cycle and apoptosis were detected by flow cytometry, the proportion of senile cells was counted by ß-galactosidase staining, the protein expression of p300, H4K12, Cyclin D1, TERT and Ki67 were detected by western blot. RESULTS: Compared with the control group, the cell cycle of CSE group and CTPB group were blocked, the apoptosis rate and early apoptosis rate were increased, the proportion of senile cells counted by ß-galactosidase staining was increased, the expression of p300 and H4K12 protein were increased, the expression of Cyclin D1, TERT and Ki67 protein were decreased. C646 could partly alleviate the damages caused by CSE. CONCLUSIONS: CSE may promote the apoptosis and senescence of EPCs by upregulating the expression of p300 and H4K12 protein, thus preventing the transition of EPCs from G1 phase to S phase, affecting telomerase synthesis, and reducing EPCs proliferation.

6.
Bioorg Chem ; 139: 106756, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37544271

RESUMO

Marine fungi are prolific source for the discovery of structurally diverse and bioactive molecules. In our search for new anti-osteoporosis compounds from deep-sea-derived fungi, we prioritized a fungus whose extract exhibited moderate activity and rich chemical diversity. The investigation of this strain afforded a class of citrinins, including three new citrinin trimers, neotricitrinols A-C (1-3), and three known dimeric/monomeric precursors (4-6). Neotricitrinols A-C (1-3) feature a unique octacyclic carbon scaffold among the few reported citrinin trimers with their absolute configurations established by spectroscopic analysis, theoretical-statistical approaches (GIAO-NMR, TDDFT-ECD/ORD calculations), DP4+ probability analysis as well as biogenetic consideration. A plausible biosynthetic pathway linking 1-3 from the common intermediate metabolite penicitrinol A (4) was proposed. Biologically, neotricitrinol B (2) showed potential anti-osteoporosis activity by promoting osteoblastogenesis and inhibiting adipogenic differentiation on primary bone mesenchymal stem cells, while displaying no cytotoxicity.


Assuntos
Citrinina , Penicillium , Citrinina/química , Citrinina/farmacologia , Penicillium/química , Espectroscopia de Ressonância Magnética , Fungos , Estrutura Molecular
7.
Sheng Li Xue Bao ; 75(4): 575-586, 2023 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-37583045

RESUMO

Obstructive sleep apnea syndrome (OSAS), a prevalent sleep disorder in children, is characterized by recurring upper airway obstruction during sleep. OSAS in children can cause intermittent hypoxia and sleep fragmentation, ultimately affect brain development and further lead to cognitive impairment if lack of timely effective intervention. In recent years, magnetic resonance imaging (MRI) and electroencephalogram (EEG) have been employed to investigate brain structure and function abnormalities in children with OSAS. Previous studies have indicated that children with OSAS showed extensive gray and white matter damage, abnormal brain function in regions such as the frontal lobe and hippocampus, as well as a significant decline in general cognitive function and executive function. However, the existing studies mainly focused on the regional activity, and the mechanism of pediatric OSAS affecting brain networks remains unknown. Moreover, it's unclear whether the alterations in brain structure and function are associated with their cognitive impairment. In this review article, we proposed two future research directions: 1) future studies should utilize the multimodal neuroimaging techniques to reveal the alterations of brain networks organization underlying pediatric OSAS; 2) further investigation is necessary to explore the relationship between brain network alteration and cognitive dysfunction in children with OSAS. With these efforts, it will be promising to identify the neuroimaging biomarkers for monitoring the brain development of children with OSAS as well as aiding its clinical diagnosis, and ultimately develop more effective strategies for intervention, diagnosis, and treatment.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Criança , Apneia Obstrutiva do Sono/complicações , Cognição , Hipóxia/complicações , Hipocampo , Lobo Frontal
8.
bioRxiv ; 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37645897

RESUMO

The human Mitochondrial RNA Splicing 2 protein (MRS2) has been implicated in Mg2+ transport across mitochondrial inner membranes, thus playing an important role in Mg2+ homeostasis critical for mitochondrial integrity and function. However, the molecular mechanisms underlying its fundamental channel properties such as ion selectivity and regulation remain unclear. Here, we present structural and functional investigation of MRS2. Cryo-electron microscopy structures in various ionic conditions reveal a pentameric channel architecture and the molecular basis of ion permeation and potential regulation mechanisms. Electrophysiological analyses demonstrate that MRS2 is a Ca2+-regulated, non-selective channel permeable to Mg2+, Ca2+, Na+ and K+, which contrasts with its prokaryotic ortholog, CorA, operating as a Mg2+-gated Mg2+ channel. Moreover, a conserved arginine ring within the pore of MRS2 functions to restrict cation movements, likely preventing the channel from collapsing the proton motive force that drives mitochondrial ATP synthesis. Together, our results provide a molecular framework for further understanding MRS2 in mitochondrial function and disease.

9.
Front Physiol ; 14: 1079736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37398906

RESUMO

Background: Sepsis associated with acute lung injury (ALI) is a common acute and severe disease with severe socioeconomic burden. The aim of this study is to explore the literatures of sepsis associated with ALI from a bibliometric perspective. Methods: Articles and reviews related to sepsis associated with ALI published from 2012 to 2021 in the Web of Science Core Collection were retrieved. Countries, affiliations, journals, authors, references, co-citation and keyword analysis in this field were visually analyzed using WOS citation reports, bibliometric.com, CtieSpace and VOSviewer software. Results: Over the last decade (2012-2021), marked progress has been made in the area of sepsis associated with ALI research. 836 papers were enrolled in this study. China accounts for the most contributors. Articles from the United States has the highest average cited. Shanghai Jiao Tong University, University of California System and Huazhong University of Science Technology were the main contributing institutions. Articles in International Immunopharmacology, Inflammation, Shock and Critical Care were cited the most. Matthay MA and Ware LB were the main contributors to this field. Inflammation and NF-κB have always been the focus of sepsis associated with ALI related research, and programmed cell death (including apoptosis, necroptosis and pyroptosis) may be the important direction of future research. Conclusion: Research on the sepsis associated with ALI is flourishing. The research on programmed cell death is a hot spot and may be a promising research field in the coming years.

10.
Nat Commun ; 14(1): 1712, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973289

RESUMO

The pannexin 2 channel (PANX2) participates in multiple physiological processes including skin homeostasis, neuronal development, and ischemia-induced brain injury. However, the molecular basis of PANX2 channel function remains largely unknown. Here, we present a cryo-electron microscopy structure of human PANX2, which reveals pore properties contrasting with those of the intensely studied paralog PANX1. The extracellular selectivity filter, defined by a ring of basic residues, more closely resembles that of the distantly related volume-regulated anion channel (VRAC) LRRC8A, rather than PANX1. Furthermore, we show that PANX2 displays a similar anion permeability sequence as VRAC, and that PANX2 channel activity is inhibited by a commonly used VRAC inhibitor, DCPIB. Thus, the shared channel properties between PANX2 and VRAC may complicate dissection of their cellular functions through pharmacological manipulation. Collectively, our structural and functional analysis provides a framework for development of PANX2-specific reagents that are needed for better understanding of channel physiology and pathophysiology.


Assuntos
Conexinas , Proteínas de Membrana , Proteínas do Tecido Nervoso , Humanos , Ânions , Transporte Biológico , Conexinas/metabolismo , Microscopia Crioeletrônica , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo
11.
J Nat Prod ; 86(1): 157-165, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36547402

RESUMO

Chemical investigation of the deep-sea-derived fungus Rhizopus sp. W23 resulted in the identification of six new (1-3, 6, 8, 9) and 12 known (4, 5, 10-19) cyclocitrinol analogues, together with one handling artifact (7), all featuring an unusual 7/7/6/5-tetracyclic scaffold and bicyclo[4.4.1] A/B rings. Norcyclocitrinoic acids A and B (1, 2) represent the second occurrence of 24,25-bisnor cyclocitrinols. Structures were assigned to new steroids on the basis of extensive spectroscopic analysis and X-ray crystallography. Compound 13 significantly enhances osteoblastogenesis and inhibits adipogenesis in mature bone marrow stromal cells at 5 µM, indicating a potential to be an antiosteoporosis lead.


Assuntos
Fungos , Esteroides , Fungos/química , Esteroides/farmacologia , Análise Espectral , Cristalografia por Raios X , Estrutura Molecular
12.
Comput Biol Med ; 151(Pt A): 106236, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36370584

RESUMO

By taking a new perspective to combine a machine learning method with an evolutionary algorithm, a new hybrid algorithm is developed to predict cancer driver genes. Firstly, inspired by the search strategy with the capability of global search in evolutionary algorithms, a gravitational kernel is proposed to act on the full range of gene features. Constructed by fusing PPI and mutation features, the gravitational kernel is capable to produce repulsion effects. The candidate genes with greater mutation effects and PPI have higher similarity scores. According to repulsion, the similarity score of these promising genes is larger than ordinary genes, which is beneficial to search for these promising genes. Secondly, inspired by the idea of elite populations related to evolutionary algorithms, the concept of vital few is proposed. Targeted at a local scale, it acts on the candidate genes associated with vital few genes. Under attraction effect, these vital few driver genes attract those with similar mutational effects to them, which leads to greater similarity scores. Lastly, the model and parameters are optimized by using an evolutionary algorithm, so as to obtain the optimal model and parameters for cancer driver gene prediction. Herein, a comparison is performed with six other advanced methods of cancer driver gene prediction. According to the experimental results, the method proposed in this study outperforms these six state-of-the-art algorithms on the pan-oncogene dataset.


Assuntos
Algoritmos , Neoplasias , Humanos , Oncogenes , Aprendizado de Máquina , Mutação , Neoplasias/genética
13.
J Healthc Eng ; 2022: 6788569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199375

RESUMO

Methods: Gene expression profiles of GSE13904, GSE26378, GSE26440, GSE65682, and GSE69528 were obtained from the National Center for Biotechnology Information (NCBI). The differentially expressed genes (DEGs) were searched using limma software package. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs and screen hub genes. Results: A total of 108 DEGs were identified in the study, of which 67 were upregulated and 41 were downregulated. 15 superlative diagnostic biomarkers (CCL5, CCR7, CD2, CD27, CD274, CD3D, GNLY, GZMA, GZMH, GZMK, IL2RB, IL7R, ITK, KLRB1, and PRF1) for sepsis were identified by bioinformatics analysis. Conclusion: 15 hub genes (CCL5, CCR7, CD2, CD27, CD274, CD3D, GNLY, GZMA, GZMH, GZMK, IL2RB, IL7R, ITK, KLRB1, and PRF1) have been elucidated in this study, and these biomarkers may be helpful in the diagnosis and therapy of patients with sepsis.


Assuntos
Biologia Computacional , Sepse , Biomarcadores , Análise de Dados , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Receptores CCR7 , Sepse/diagnóstico , Sepse/genética
14.
Eur J Pediatr ; 181(12): 4019-4037, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36109390

RESUMO

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.


Assuntos
Antipiréticos , COVID-19 , Insuficiência Respiratória , Adolescente , Criança , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Imunoglobulinas Intravenosas , Oxigênio
15.
Nanomaterials (Basel) ; 12(18)2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36144943

RESUMO

Both MXene and black phosphorus (BP), which actg as hot two-dimensional (2D) materials, have unique optical properties and important applications for nano-micro optical devices. Here, a composite MXene/BP-based metasurface, consisting of Ti3C2Tx and BP layers, is proposed for investigating the optical responses and electric field by using the finite-difference time-domain numerical simulation method in the microwave band. The research results show that the Fano resonance-like spectra can be observed when the coupling of surface plasmons (SPs) on the BP and MXene layers appears. Furthermore, the field enhancement, based on the Fano resonance-like optical responses, can be improved by an order of magnitude through adjusting the structural parameters and the polarization direction of incident light for the proposed metasurface. The findings may provide important theoretical insights into the design and realization of high-performance plasmonic devices.

16.
iScience ; 25(7): 104647, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35800765

RESUMO

Silicosis is caused by inhalation of crystalline silica dust particles and known as one of the most serious occupational diseases worldwide. However, little is known about intrinsic factors leading to disease susceptibility. Single-cell sequencing of bronchoalveolar lavage fluid cells of mine workers with silicosis and their co-workers who did not develop silicosis revealed that the impaired interferon (IFN)-γ signaling in myeloid cells was strongly associated with the occurrence of silicosis. Global or myeloid cell-specific deletion of interferon γ receptor (IFN-γR) markedly enhanced the crystalline silica-induced pulmonary injury in wild-type but not in NLRP3 deficient mice. In vitro, IFN-γ priming of macrophages suppressed the crystalline silica-induced NLRP3 inflammasome activation partly by inducing the formation of spacious phagosomes with relatively reduced ratio of crystalline silica/phagosomal areas volumes to resistant crystalline silica-induced lysosomal membrane damage. Thus, these findings provide molecular insights into the intricate mechanisms underlying innate immunity-mediated host responses to environmental irritants.

17.
Front Immunol ; 13: 911152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720285

RESUMO

Sepsis, a systemic inflammatory response disease, is the most severe complication of infection and a deadly disease. High mobility group proteins (HMGs) are non-histone nuclear proteins binding nucleosomes and regulate chromosome architecture and gene transcription, which act as a potent pro-inflammatory cytokine involved in the delayed endotoxin lethality and systemic inflammatory response. HMGs increase in serum and tissues during infection, especially in sepsis. A growing number of studies have demonstrated HMGs are not only cytokines which can mediate inflammation, but also potential therapeutic targets in sepsis. To reduce sepsis-related mortality, a better understanding of HMGs is essential. In this review, we described the structure and function of HMGs, summarized the definition, epidemiology and pathophysiology of sepsis, and discussed the HMGs-related mechanisms in sepsis from the perspectives of non-coding RNAs (microRNA, long non-coding RNA, circular RNA), programmed cell death (apoptosis, necroptosis and pyroptosis), drugs and other pathophysiological aspects to provide new targets and ideas for the diagnosis and treatment of sepsis.


Assuntos
Sepse , Citocinas/genética , Proteínas de Grupo de Alta Mobilidade/genética , Humanos , Inflamação , Nucleossomos , Sepse/metabolismo
18.
Science ; 376(6593): 609-615, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35511979

RESUMO

Heatstroke is a heat stress-induced, life-threatening condition associated with circulatory failure and multiple organ dysfunctions. If global warming continues, heatstroke might become a more prominent cause of mortality worldwide, but its pathogenic mechanism is not well understood. We found that Z-DNA binding protein 1 (ZBP1), a Z-nucleic acid receptor, mediated heatstroke by triggering receptor-interacting protein kinase 3 (RIPK3)-dependent cell death. Heat stress increased the expression of ZBP1 through heat shock transcription factor 1 (HSF1) and activated ZBP1 through a mechanism independent of the nucleic acid sensing action. Deletion of ZBP1, RIPK3, or both mixed lineage kinase domain-like (MLKL) and caspase-8 decreased heat stress-induced circulatory failure, organ injury, and lethality. Thus, ZBP1 appears to have a second function that orchestrates host responses to heat stress.


Assuntos
Golpe de Calor , Ácidos Nucleicos , Morte Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética
19.
BMC Med Res Methodol ; 22(1): 89, 2022 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-35369859

RESUMO

BACKGROUND: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. RESULT: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining five recommendations ranged between 10 and 83%. Six of the ten recommendations used COVID-19 preprints as evidence support, and up to 50% of the studies with direct evidence on COVID-19 were preprints. CONCLUSIONS: In order to respond to public health emergencies, the development of RAG also requires a clear and transparent formulation process, usually using a large amount of indirect and non-peer-reviewed evidence to support the formation of recommendations. Strict following of the WHO RAG handbook does not only enhance the transparency and clarity of the guideline, but also can speed up the guideline development process, thereby saving time and labor costs.


Assuntos
COVID-19 , COVID-19/epidemiologia , Criança , Surtos de Doenças , Guias como Assunto , Humanos , Saúde Pública
20.
BMC Urol ; 22(1): 30, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35255882

RESUMO

BACKGROUND: Renal colic is a surgical emergency in pregnancy that is caused by a range of non-obstetric factors and known to occur more frequently during the second and third trimesters. Several studies have reported that up to 70-80% of stones pass spontaneously during pregnancy. There are some patients will not pass their stones and will ultimately require surgical intervention. Through retrospective analysis of the clinical data of 212 pregnant women with renal colic, the predictive factors of pregnant women with renal colic in need of surgical intervention were determined. METHODS: We conducted a retrospective review of 212 pregnant women presenting with renal colic between 1st January 2009 and 31st December 2020. Univariate and multivariate analyses identified a range of predictive variables for surgical intervention. In addition, we used receiver operating characteristic curve analysis to evaluate the predictive power of our model and created a nomogram for clinical application. RESULTS: Of the 212 patients presenting with acute renal colic in pregnancy, 100 patients (47.2%) underwent surgical intervention and 112 patients (52.8%) were treated conservatively. Univariate analysis identified significant differences between the two groups with regards to fever, the duration of pain, white blood cells, C-reactive protein, ureteral stone size, hydronephrosis, and stone location. Multivariate analysis further identified a number of independent predictors for surgical intervention, including fever, a duration of pain ≥ 4 days, a ureteral stone size ≥ 8 mm, and moderate or severe hydronephrosis. CONCLUSIONS: We identified several independent predictors for surgical intervention for renal colic in pregnancy. Fever, a duration of pain ≥ 4 days, a ureteral stone size ≥ 8 mm, and moderate/severe hydronephrosis, play significant roles in predicting surgical intervention. Our nomogram can help to calculate the probability of surgical intervention in a simple and efficient manner. Prospective studies are now required to validate our model.


Assuntos
Complicações na Gravidez/cirurgia , Cólica Renal/cirurgia , Adulto , Feminino , Humanos , Gravidez , Complicações na Gravidez/etiologia , Cólica Renal/etiologia , Estudos Retrospectivos
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