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1.
Small ; : e2400164, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573934

RESUMO

Captured by high theoretical capacity and low-cost, Sodium-Sulfur (Na-S) batteries have been deemed as promising energy-storage systems. However, their electrochemical properties, containing both cycling and rate properties, still suffer from the notorious "shuttle effect" of polysulfide. Herein, through the effective regulation of pore sizes, a series of S@SiO2 cathode materials are obtained. Benefitting from the abundant pore channels of SiO2 particles, the sulfur loading is as high as 76.3%. Importantly, a suitable pore size can lead to adequate reaction and rapid diffusion behaviors, resulting in excellent electrochemical performances. Specifically, at 2.0 A g-1, the initial capacity of the as-optimized sample can be up to 1370.6 mAh g-1. Surprisingly, even after 1050 cycles, it could achieve a high reversible capacity of 1280.8 mAh g-1 with an attenuation rate of 0.089%. At 5.0 A g-1, after 500 cycles, the capacity can still remain ≈ 1132.6 mAh g-1 (capacity retention rate, 97.5%). Given this, the work is anticipated to offer an effective strategy for advanced electrodes for Na-S batteries.

2.
J Inflamm Res ; 17: 2173-2193, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617383

RESUMO

The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.

3.
bioRxiv ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38585812

RESUMO

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disassembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find assembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

4.
Expert Rev Proteomics ; 21(1-3): 115-123, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38372668

RESUMO

INTRODUCTION: Around 20% of individuals diagnosed with acute pancreatitis (AP) may develop severe acute pancreatitis (SAP), possibly resulting in a mortality rate ranging from 15% to 35%. There is an urgent need to thoroughly understand the molecular phenotypes of SAP resulting from diverse etiologies. The field of translational research on AP has seen the use of several innovative proteomic methodologies via the ongoing improvement of isolation, tagging, and quantification methods. AREAS COVERED: This paper provides a comprehensive overview of differentially abundant proteins (DAPs) identified in AP by searching the PubMed/MEDLINE database (2003-2023) and adds significantly to the current theoretical framework. EXPERT OPINION: DAPs for potentially diagnosing AP based on proteomic identification need to be confirmed by multi-center studies that include larger samples. The discovery of DAPs in various organs at different AP stages via proteomic technologies is essential better to understand the pathophysiology of AP-related multiple organ dysfunction syndrome. Regarding the translational research of AP, novel approaches like single-cell proteomics and imaging using mass spectrometry may be used as soon as they become available.


Assuntos
Pancreatite , Humanos , Pancreatite/diagnóstico , Pancreatite/complicações , Pancreatite/metabolismo , Proteômica , Doença Aguda , Insuficiência de Múltiplos Órgãos
5.
Sci Rep ; 14(1): 4342, 2024 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-38383583

RESUMO

Surgical intervention is typically recommended for thoracic ossification of the ligamentum flavum (TOLF). This study aimed to evaluate the efficacy and safety of a novel non-coaxial one-hole split endoscope (OSE) technique for treating TOLF. We performed OSE procedure on 13 patients with TOLF from June 2022 to July 2023. The mean operative time was 117.5 ± 15.4 min. VAS scores for lower limbs decreased from 6.5 ± 0.8 preoperative to 1.6 ± 0.4 at the last follow-up (P < 0.001). ODI scores improved from 62.4 ± 5.7 preoperative to 18.6 ± 2.2 at the last follow-up (P < 0.001), and mJOA scores increased from 5.1 ± 1.6 preoperative to 8.4 ± 1.5 at the latest follow-up (P < 0.001). All patients achieved ASIA scale grade D or E at the final follow-up, except for two patients remained residual limb numbness. None of the thirteen patients suffered from severe perioperative complications. The OSE technique proves to be a safe and effective procedure for treating TOLF or even with dura mater ossification, characterized by minimal surgical trauma, relatively smooth learning curve and flexible operation.


Assuntos
Ligamento Amarelo , Ossificação Heterotópica , Humanos , Osteogênese , Ossificação Heterotópica/cirurgia , Ossificação Heterotópica/complicações , Ligamento Amarelo/cirurgia , Vértebras Torácicas/cirurgia , Endoscópios , Resultado do Tratamento , Estudos Retrospectivos
6.
Trials ; 25(1): 130, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38365704

RESUMO

INTRODUCTION: Lung cancer is the most common cancer in China, with the highest mortality rate. Surgery is the primary treatment for early lung cancer. However, patients with lung cancer have a heavy burden of symptoms within 3 months after surgery, which seriously affects their quality of life (QOL). The symptom management model based on the patient-reported outcome (PRO) is considered the best caregiving model. The clinical evidence about the symptom management of lung cancer within 3 months after the operation is very limited. Herein, we propose a randomized controlled trial to evaluate the PRO score-based monitoring and alert system for follow-up on psychological and physiological symptoms of lung cancer patients within 3 months after surgery and further investigate the effect of intervention measures based on this PRO score-based system. METHODS AND ANALYSIS: This multicenter, open-label, randomized, parallel superiority trial will be conducted at four hospitals in China. A total of 440 lung cancer patients will be recruited in this study, who will be randomly assigned to the intervention group or the control group in a ratio of 1:1. Any of the target symptoms reaches the preset threshold (score ≥ 4), the patients will accept the symptom management advices based on the PRO. The patients in the control group will follow the current standard procedure of symptom management. The symptom management system is an electronic management system based on WeChat mini programs. All patients will be evaluated for symptoms through the lung cancer module of the MDASI lung cancer-specific scale on the day before surgery, days 1, 3, 5, and 7 after surgery, and once a week during the 12-week post-discharge period. Simultaneously, the EORTC QLQ-C30 scale will be used to evaluate patients' quality of life at baseline and the fourth and twelfth week after the surgery. The mean number of symptom threshold events of the intervention and the control groups were compared by t-test, and the changes of PRO were compared by a mixed effect model. The primary endpoint has been set as the 12-week post-discharge period. DISCUSSION: This study will test the feasibility of the symptom management system based on the mobile social media applet in postoperative caregiving and the efficacy of psychiatrist-assisted treatment and provide evidence in managing the symptoms of patients in the medium and long term. TRIALS REGISTRATION: Trials registration number: ChiCTR 2200058876, Registered 18 April 2022.


Assuntos
COVID-19 , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , SARS-CoV-2 , Qualidade de Vida , Assistência ao Convalescente , Alta do Paciente , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
7.
Chem Commun (Camb) ; 60(22): 3059-3062, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38384238

RESUMO

A chemical-physical investigation proved that the loss of active Li represents the main mechanism of capacity-fading in spent LiFePO4. Given this, functional Li2CuO2-coated separators were fabricated from spent Cu foil and found to contribute to the regeneration of spent LiFePO4 in a full-cell system. This study presents a novel method for cathode/Cu foil recovery.

8.
J Biophotonics ; 17(2): e202300289, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010284

RESUMO

Photoacoustic imaging (PAI) has been applied to many biomedical applications over the past decades. However, the received PA signal usually suffers from poor SNR. Conventional solution of employing higher-power laser, or doing long-time signal averaging, may raise the system cost, time consumption, and tissue damage. Another strategy is de-noising algorithm design. In this paper, we propose a gradient-based adaptive wavelet de-noising method, which sets the energy gradient mutation point of low-frequency wavelet components as the threshold. We conducted simulation, ex-vivo and in-vivo experiments using acoustic-resolution PAM. The quality of de-noised PA image/signal by our proposed algorithm has improved by at least 30%, in comparison to the traditional signal denoising algorithms, which produces better contrast and clearer details. Moreover, it produces good results when dealing with multi-layer structures. The proposed de-noising method provides potential to improve the SNR of PA signal under single-shot low-power laser illumination for biomedical applications in vivo.


Assuntos
Técnicas Fotoacústicas , Diagnóstico por Imagem , Algoritmos , Simulação por Computador
9.
J Biol Chem ; 300(2): 105531, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072051

RESUMO

Heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2) is a human ribonucleoprotein that transports RNA to designated locations for translation via its ability to phase separate. Its mutated form, D290V, is implicated in multisystem proteinopathy known to afflict two families, mainly with myopathy and Paget's disease of bone. Here, we investigate this mutant form of hnRNPA2 by determining cryo-EM structures of the recombinant D290V low complexity domain. We find that the mutant form of hnRNPA2 differs from the WT fibrils in four ways. In contrast to the WT fibrils, the PY-nuclear localization signals in the fibril cores of all three mutant polymorphs are less accessible to chaperones. Also, the mutant fibrils are more stable than WT fibrils as judged by phase separation, thermal stability, and energetic calculations. Similar to other pathogenic amyloids, the mutant fibrils are polymorphic. Thus, these structures offer evidence to explain how a D-to-V missense mutation diverts the assembly of reversible, functional amyloid-like fibrils into the assembly of pathogenic amyloid, and may shed light on analogous conversions occurring in other ribonucleoproteins that lead to neurological diseases such as amyotrophic lateral sclerosis and frontotemporal dementia.


Assuntos
Microscopia Crioeletrônica , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Modelos Moleculares , Humanos , Domínios Proteicos , Mutação , Concentração de Íons de Hidrogênio , Estabilidade Proteica , Estrutura Terciária de Proteína , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/química , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo
10.
J Med Virol ; 95(12): e29272, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38054501

RESUMO

The impact of severe acute respiratory syndrome coronavirus 2 infection on the potential development of pancreatitis is a subject of ongoing debate within academic discourse. Establishing a causal link between COVID-19 and pancreatitis may not be fully supported by relying only on retrospective studies or case reports. This study examined the relationship between COVID-19 phenotypes and pancreatitis by Mendelian randomization (MR) method. The identification of instrumental variables (single nucleotide polymorphisms) that exhibit a robust association with the COVID-19 phenotypes was accomplished through a meticulous process of rigorous screening procedures. We included acute pancreatitis and chronic pancreatitis (CP) as the outcomes in the MR analysis, even though no definitive studies exist between COVID-19 and CP. A direct causal relationship between genetically predicted COVID-19 phenotypes and pancreatitis risk cannot be established. There is an ongoing debate over the designation of COVID-19 as a definitive cause of pancreatitis.


Assuntos
COVID-19 , Pancreatite , Humanos , Doença Aguda , COVID-19/complicações , Estudo de Associação Genômica Ampla , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Análise da Randomização Mendeliana
11.
PNAS Nexus ; 2(12): pgad402, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38077690

RESUMO

We previously presented a bioinformatic method for identifying diseases that arise from a mutation in a protein's low-complexity domain that drives the protein into pathogenic amyloid fibrils. One protein so identified was the tropomyosin-receptor kinase-fused gene protein (TRK-fused gene protein or TFG). Mutations in TFG are associated with degenerative neurological conditions. Here, we present experimental evidence that confirms our prediction that these conditions are amyloid-related. We find that the low-complexity domain of TFG containing the disease-related mutations G269V or P285L forms amyloid fibrils, and we determine their structures using cryo-electron microscopy (cryo-EM). These structures are unmistakably amyloid in nature and confirm the propensity of the mutant TFG low-complexity domain to form amyloid fibrils. Also, despite resulting from a pathogenic mutation, the fibril structures bear some similarities to other amyloid structures that are thought to be nonpathogenic and even functional, but there are other factors that support these structures' relevance to disease, including an increased propensity to form amyloid compared with the wild-type sequence, structure-stabilizing influence from the mutant residues themselves, and double-protofilament amyloid cores. Our findings elucidate two potentially disease-relevant structures of a previously unknown amyloid and also show how the structural features of pathogenic amyloid fibrils may not conform to the features commonly associated with pathogenicity.

12.
J Environ Manage ; 348: 119405, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37924693

RESUMO

municipal solid waste incineration (MSWI) fly ash partially replaces cement to solidify sediment, and then can be used as intermediate cover materials in landfill as one of the resources utilization ways of MSWI fly ash and sediment. The strength and the semi-dynamic leaching characteristics of MSWI fly ash solidified sediment under hydrochloric acid attack at different pH were studied by means of unconfined compressive strength (UCS), semi-dynamic leaching, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA). Results revealed that the UCS strength increased as the curing age and cement content increased. When the curing content is 50% and the replacement ratio of MSWI fly ash is 75% and 80%, the UCS of 7 d can be greater than 50 kPa. The primary contribution to the strength development was from silicic acid gels such as calcium silicate hydrate (C-S-H) and carbonates. Notably, the leaching behavior of Zn and Cu within the solidified sediment underwent substantial alterations. The leaching amount of heavy metals in a strong acidic environment (pH = 2) is significantly greater than that in a weak acidic (pH = 4) and neutral (pH = 7) environment. Conversely, minimal disparities were observed in the leaching characteristics of Zn and Cu between the weakly acidic and neutral environments. Ca(OH)2, C-S-H and carbonate exhibits a remarkable acid-resistant buffering capacity in the solidified sediment. The obvious diffusion coefficient (Dobs) was less than 10-9 m2/s in semi-dynamic leaching tests. Moreover, the mobility of Zn and Cu surpassing 12.5, coupled with a leaching index exceeding 8, further attests to the favorable S/S outcome achieved. Based on these findings, the solidified material is confidently recommended to be used as suitable landfill middle soil cover material.


Assuntos
Metais Pesados , Eliminação de Resíduos , Cinza de Carvão/química , Incineração , Resíduos Sólidos/análise , Material Particulado , Carbono/química , Metais Pesados/análise
13.
Int J Nanomedicine ; 18: 6743-6761, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026528

RESUMO

Background: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear. Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO. Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats. Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO.


Assuntos
Lesão Pulmonar Aguda , Emodina , Exossomos , MicroRNAs , Pancreatite , Ratos , Animais , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Emodina/farmacologia , Doença Aguda , Exossomos/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , MicroRNAs/genética , MicroRNAs/metabolismo
14.
Discov Med ; 35(178): 823-830, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37811620

RESUMO

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is the gold standard surgery used to treat cervical degenerative disease. Dysphagia and hoarseness are the two most common complications that occur after anterior cervical surgery (ACS). In this study, we aim to evaluate the early effects of longus colli muscle (LCM) and anterior longitudinal ligament (ALL) reconstructions on swallowing function after ACS. METHODS: We recruited 91 patients (35 males and 56 females; mean age: 49.41 ± 8.60 years [range: 26-72 years]) who have undergone either ACDF or anterior cervical corpectomy and fusion (ACCF) between August 2019 and October 2021. Patients were divided into LCM and ALL suture group (Group A), and LCM and ALL non-suture group (Group B). Assessments of the incidence of dysphagia and the swallowing quality of life (SWAL-QOL) were completed in 2 days, 1 week, 1 month, 3 months and 6 months after surgery. Average prevertebral soft tissue thickness (APSTT) were measured on lateral cervical spine radiographs taken with X-rays 2 days, 1 month, 3 months and 6 months after surgery. RESULTS: In the 2-day, 1-week and 1-month postoperative follow-up, the incidence of dysphagia in group A was significantly lower than that in group B (p < 0.05), and the SWAL-QOL scores of group A were significantly higher than those of group B (p < 0.05). In the 3-month and 6-month postoperative follow-up, no significant differences were found between groups A and B in terms of the incidence of dysphagia (p > 0.05). In the 6-month postoperative follow-up, no significant differences were found between the groups in terms of SWAL-QOL scores (p > 0.05). There were no significant differences in APSTT between groups during postoperative follow-up (p > 0.05). CONCLUSION: The reconstructions of LCM and ALL in ACS can effectively improve short-term postoperative swallowing function.


Assuntos
Transtornos de Deglutição , Deglutição , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Seguimentos , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Qualidade de Vida , Resultado do Tratamento , Ligamentos Longitudinais/cirurgia , Músculos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
15.
Opt Express ; 31(17): 27136-27146, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710794

RESUMO

This paper presents a method for measuring the optical assembly results based on multi-beam biaxial LiDAR. This method analyzes the optical assembly parameters of a LiDAR system affecting the LiDAR operation, and an experimental measurement system is built using a collimator to simulate the infinity imaging field. An InGaAs infrared camera is used to take pictures of the laser spot from the LiDAR transmitter and receiver, and then fit the laser spot images with Gaussian equations to calculate the biaxial LiDAR optical assembly results. Finally, the possible effecting factors of LiDAR alignment results are analyzed. This method is experimentally proven to achieve the measurement of the optical assembly results of a large scale multi-beam LiDAR. The possibility of further optimizing the measurement method by shaping the transmit laser is also reported.

16.
Sensors (Basel) ; 23(18)2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37765990

RESUMO

Lidar presents a promising solution for bird surveillance in airport environments. However, the low observation refresh rate of Lidar poses challenges for tracking bird targets. To address this problem, we propose a gated recurrent unit (GRU)-based interacting multiple model (IMM) approach for tracking bird targets at low sampling frequencies. The proposed method constructs various GRU-based motion models to extract different motion patterns and to give different predictions of target trajectory in place of traditional target moving models and uses an interacting multiple model mechanism to dynamically select the most suitable GRU-based motion model for trajectory prediction and tracking. In order to fuse the GRU-based motion model and IMM, the approximation state transfer matrix method is proposed to transform the prediction of GRU-based network into an explicit state transfer model, which enables the calculation of the models' probability. The simulation carried out on an open bird trajectory dataset proves that our method outperforms classical tracking methods at low refresh rates with at least 26% improvement in tracking error. The results show that the proposed method is effective for tracking small bird targets based on Lidar systems, as well as for other low-refresh-rate tracking systems.

17.
Int J Mol Sci ; 24(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37569514

RESUMO

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP).


Assuntos
Lesão Pulmonar Aguda , Pancreatite , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Sepse , Humanos , Glucocorticoides/uso terapêutico , Doença Aguda , Pancreatite/complicações , Síndrome do Desconforto Respiratório/patologia , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/complicações , Sepse/complicações
18.
Acta Pharmacol Sin ; 44(10): 2125-2138, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37277492

RESUMO

Parthanatos is a type of programmed cell death dependent on hyper-activation of poly (ADP-ribose) polymerase 1 (PARP-1). SIRT1 is a highly conserved nuclear deacetylase and often acts as an inhibitor of parthanatos by deacetylation of PARP1. Our previous study showed that deoxypodophyllotoxin (DPT), a natural compound isolated from the traditional herb Anthriscus sylvestris, triggered glioma cell death via parthanatos. In this study, we investigated the role of SIRT1 in DPT-induced human glioma cell parthanatos. We showed that DPT (450 nmol/L) activated both PARP1 and SIRT1, and induced parthanatos in U87 and U251 glioma cells. Activation of SIRT1 with SRT2183 (10 µmol/L) enhanced, while inhibition of SIRT1 with EX527 (200 µmol/L) or knockdown of SIRT1 attenuated DPT-induced PARP1 activation and glioma cell death. We demonstrated that DPT (450 nmol/L) significantly decreased intracellular NAD+ levels in U87 and U251 cells. Further decrease of NAD+ levels with FK866 (100 µmol/L) aggravated, but supplement of NAD+ (0.5, 2 mmol/L) attenuated DPT-induced PARP1 activation. We found that NAD+ depletion enhanced PARP1 activation via two ways: one was aggravating ROS-dependent DNA DSBs by upregulation of NADPH oxidase 2 (NOX2); the other was reinforcing PARP1 acetylation via increase of N-acetyltransferase 10 (NAT10) expression. We found that SIRT1 activity was improved when being phosphorylated by JNK at Ser27, the activated SIRT1 in reverse aggravated JNK activation via upregulating ROS-related ASK1 signaling, thus forming a positive feedback between JNK and SIRT1. Taken together, SIRT1 activated by JNK contributed to DPT-induced human glioma cell parthanatos via initiation of NAD+ depletion-dependent upregulation of NOX2 and NAT10.


Assuntos
Glioma , Parthanatos , Sirtuína 1 , Humanos , Glioma/tratamento farmacológico , Acetiltransferases N-Terminal/genética , Acetiltransferases N-Terminal/metabolismo , NAD/metabolismo , NADPH Oxidase 2/metabolismo , Parthanatos/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Regulação para Cima
19.
Microbiol Spectr ; 11(4): e0366422, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37338348

RESUMO

The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased Firmicutes/Bacteroidetes ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. IMPORTANCE Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.


Assuntos
Lesão Pulmonar Aguda , Microbioma Gastrointestinal , Pancreatite , Camundongos , Animais , Pancreatite/tratamento farmacológico , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas Quinases Ativadas por AMP/uso terapêutico , Doença Aguda , Estudos Prospectivos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Ácidos Graxos Voláteis
20.
J Mol Biol ; 435(14): 168142, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37356907

RESUMO

Although nascent RNA profiling data are widely used in transcriptional regulation studies, the development and standardization of data processing pipeline lags far behind RNA-seq. We are filling this gap by establishing the nASAP web server (https://grobase.top/nasap/) to provide practical quality evaluation and comprehensive analysis of nascent RNA datasets. In nASAP, four customized analysis modules are provided, including i) quality assessment, which summarizes the sequencing statistics, mapping ratio, and evaluates RNA integrity and mRNA contamination; ii) quantification analysis for mRNAs, lncRNAs and eRNAs; iii) pausing analysis across the whole genome based on sequencing reads distribution; and iv) network analysis to better understand the gene regulatory mechanism by obtaining annotated enhancer-promoter interactomes. The nASAP is user-friendly and outperforms the existing pipeline for quality control of nascent RNA profiling data. We anticipate that nASAP, which eases both basic and advanced analysis of nascent RNA data, will be extremely useful in various fields.


Assuntos
Perfilação da Expressão Gênica , RNA Mensageiro , Software , Análise de Dados , Regulação da Expressão Gênica , RNA Mensageiro/genética , Análise de Sequência de RNA
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