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1.
BMC Pulm Med ; 21(1): 363, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763680

RESUMO

BACKGROUND: Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia. METHODS: This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1-9 days of the illness course) and the late BAL layer (received BAL within 10-14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups. RESULTS: Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p < 0.05). However, in the severe group, there were no statistically significant differences in the fever and hospital duration between patients who received BAL early and those who received BAL later. However, the need for mechanical ventilation and the incidence of BAL complications, such as new need for oxygen, were higher in patients who received BAL early than in those who received BAL later in the severe group (p < 0.05). CONCLUSION: For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications.

2.
Org Lett ; 23(22): 8843-8846, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34730988

RESUMO

The first total synthesis of (±)-furanether A, which exhibits good antifeedant activity, has been concisely achieved in 13 linear steps. Notably, the key rigid tetracyclic skeleton containing a 1-methyl-8-oxabicyclo[3.2.1]octane moiety with two vicinal quaternary carbon centers was rapidly constructed in one step through a unique tandem C-H oxidation/oxa-[3,3] Cope rearrangement/aldol cyclization sequence.

3.
Quant Imaging Med Surg ; 11(11): 4583-4593, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34737925

RESUMO

Background: Fresh ischemic lesions (FILs) can occur in both the brain's gray matter (GM) and white matter (WM), with each location signifying a different prognosis for patients. This study aims to investigate the application of ultra-high b value diffusion-weighted imaging (DWI) in distinguishing FILs in these two areas via a comparative study with routine and high b value DWI. Methods: Multiple b value DWI (b=0, 500, 1,000, 2,000, 4,000, 6,000, 8,000, 10,000 s/mm2) was performed on 47 patients with suspected acute ischemic stroke (AIS). Apparent diffusion coefficient (ADC) maps, including ADC500, ADC1,000, ADC2,000, ADC4,000, ADC6,000, ADC8,000, and ADC10,000, were calculated, and the mean ADC value of the FILs in the GM and WM on each map was obtained by referring to the structural magnetic resonance imaging (MRI). ADC value differences of the FILs in the GM and WM were compared using Mann-Whitney U tests, and receiver operating characteristic (ROC) curves evaluated the diagnostic efficiency of each ADC value in distinguishing FILs in the two areas. Results: In the enrolled 34 patients, 145 FILs were identified, of which 42 involved the GM, 87 the WM, and 16 both the GM and WM. A total of 161 regions were delineated, 58 in the GM and 103 in the WM. The values of FILs in the WM on ADC2,000, ADC4,000, ADC6,000, ADC8,000, and ADC10,000 maps were significantly lower than those in the GM (P=0.007, P<0.001, P<0.001, P<0.001 and P<0.001, respectively), while no significant differences were found on ADC500 and ADC1,000 maps (P=0.427 and P=0.225, respectively). ROC curves demonstrated that the area under the curve (AUC) paralleled the increasing b value, ascending from ADC500 to ADC10,000 (0.538, 0.558, 0.629, 0.766, 0.827, 0.859, 0.872, in that order). Conclusions: Ultra-high b value DWI is extremely sensitive to the slight diffusion difference between FILs in the GM and the WM. Its sensitivity parallels the increasing b value, indicating its clinical advantage in identifying the microstructure of FILs.

4.
Adv Mater ; : e2107327, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762328

RESUMO

Liquid gating membranes have been demonstrated to show unprecedented properties of dynamicity, stability, adaptivity, and stimulus-responsiveness. Most recently, smart liquid gating membranes have attracted increasing attention to bring some brand-new properties for real-world applications, and various environment-driven systems have been created. Here, a self-driven system of a smart liquid gating membrane is further developed, by designing a new liquid gating magnetoelastic membrane-based system with reversible meniscus-shaped deformations, and it is not subject to the complex gating liquid restriction of magnetorheological fluid. Compared with other systems, this magnetic responsive self-driven system has the advantage that it provides a universal and convenient way to realize active regulation of gas/liquid release. Experiments and theoretical calculations demonstrate the stability, the non-fouling behavior, and the tunability of the system. In addition, this system can be used to perfectly open and close gas transport, and the gating pressure threshold for the liquid release can be reduced under the same conditions. Based on the above capabilities, combined with the fast and three-dimensional contactless operation, it will be of benefit in fields ranging from visible gas/liquid mixture content monitoring and energy-saving multiphase separation, remote fluid release and beyond. This article is protected by copyright. All rights reserved.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 844-848, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622603

RESUMO

Objective: To compare and analyze the clinical manifestations and sleep structure of children with obstructive sleep apnea-hypopneasyndrome (OSAHS) with different body mass index (BMI). Methods: 452 children who were diagnosed with OSAHS between December 2016 and February 2021 by the Department of Respiratory Medicine, Children's Hospital of Soochow University were included in the study. All of them did polysomnography (PSG). They were divided, according to their BMI, into the normal BMI group, the overweight group, and the obesity group. Their clinical data and PSG results were collected. Results: 287 boys (63.5%) and 165 girls (36.5%) were enrolled, with their age ranging between 3 and 15, and the median age being 5.5 (4.5, 7.0). Their BMI ranged between 12.09 kg/m 2 and 38.48 kg/m 2, with the median being 16.29 kg/m 2. 275 cases (60.8%) had normal BMI, 76 cases (16.8%) were overweight, and 101 cases (22.3%) were obese. There was no significant difference in the distribution of clinical manifestations and severity of OSAHS among the three groups. The duration and proportion of rapid eye movement (REM) stage sleep in the obese group was lower than that of the overweight and the normal BMI groups ( P<0.05). The lowest oxyhemoglobin saturation (LSaO 2) of children in the overweight group was lower than that of the normal BMI group ( P=0.050). The oxygen desaturation index (ODI) of the obese group was higher than that of the normal BMI and the overweight groups ( P<0.05). Conclusion: Obesity worsens the degree of hypoxia in children with OSAHS and affects their sleep structure.


Assuntos
Apneia Obstrutiva do Sono , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Polissonografia , Sono , Apneia Obstrutiva do Sono/complicações , Sono REM
6.
Beilstein J Org Chem ; 17: 2488-2495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646397

RESUMO

A copper-catalyzed mono-selective C-H amination of ferrocenes assisted by 8-aminoquinoline is presented here. A range of amines, including bioactive molecules, were successfully installed to the ortho-position of ferrocene amides with high efficiency under mild conditions. A range of functionalized ferrocenes were compatible to give the aminated products in moderate to good yields. The gram-scale reaction was smoothly conducted and the directing group could be removed easily under basic conditions.

7.
Arch Microbiol ; 203(10): 6021-6031, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34698880

RESUMO

A Gram-stain-negative, aerobic, and yellow-pigmented bacterium, designated A3-108T, was isolated from seawater of the West Pacific Ocean. Cells were non-motile and rod-shaped, with carotenoid-type pigments. Strain A3-108T grew at pH 6.0-8.5 (optimum 6.5) and 15-40 °C (optimum 28 °C), in the presence of 0.5-10% (w/v) NaCl (optimum 1.0%). It possessed the ability to produce H2S. Based on the 16S rRNA gene analysis, strain A3-108T exhibited highest similarity with Aureisphaera salina A6D-50T (90.6%). Phylogenetic analysis shown that strain A3-108T affiliated with members of the family Flavobacteriaceae and represented an independent lineage. The principal fatty acids were iso-C15:0, iso-C17:0 3-OH, iso-C15:1 G, and summed feature 3 (C16:1ω7c and/or C16:1ω6c). The sole isoprenoid quinone was MK-6. The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, one unidentified aminolipid and one unidentified lipid. The ANIb, in silico DDH and AAI values among the genomes of strain A3-108T and three reference strains were 67.3-71.1%, 18.7-22.1%, and 58.8-71.4%, respectively. The G + C content was 41.0%. Distinctness of the phylogenetic position as well as differentiating chemotaxonomic and other phenotypic traits revealed that strain A3-108T represented a novel genus and species of the family Flavobacteriaceae, for which the name Luteirhabdus pelagi gen. nov., sp. nov. is proposed (type strain, A3-108T = CGMCC 1.18821T = KCTC 82563T).


Assuntos
Flavobacteriaceae , Técnicas de Tipagem Bacteriana , DNA Bacteriano , Ácidos Graxos , Flavobacteriaceae/genética , Oceano Pacífico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2
8.
Org Lett ; 23(20): 7910-7915, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34605653

RESUMO

A Pd(II)-catalyzed enantioselective C-H alkynylation of 2-(arylsulfinyl)pyridines via kinetic resolution using cheap and commercially available l-pGlu-OH as a chiral ligand is reported. A wide range of 2-(arylsulfinyl)pyridines were compatible with this protocol, giving the alkynylation products and recovered sulfoxides in high yields with high enantioselectivities (up to 99% ee). Furthermore, the enantioenriched products can be easily transformed to several other types of chiral sulfoxide scaffolds with the retention of enantiopurity.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34665909

RESUMO

A divergent synthesis of skeletally distinct arboridinine and arborisidine was achieved. The central divergent strategy was inspired by the divergent biosynthetic cyclization mode of arboridinine and arborisidine and their hidden topological connection. The branch point was reached through a Michael and Mannich cascade process. A site-selective intramolecular Mannich reaction was developed to construct the tetracyclic core of arboridinine, while a site-selective intramolecular α-amination of ketone was used to access the tetracyclic core of arborisidine. A strategic Peterson olefination through intramolecular nucleophile delivery was able to set up the exocyclic olefin of arboridinine.

10.
Brief Bioinform ; 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698349

RESUMO

Target identification of small molecules is an important and still changeling work in the area of drug discovery, especially for botanical drug development. Indistinct understanding of the relationships of ligand-protein interactions is one of the main obstacles for drug repurposing and identification of off-targets. In this study, we collected 9063 crystal structures of ligand-binding proteins released from January, 1995 to April, 2021 in PDB bank, and split the complexes into 5133 interaction pairs of ligand atoms and protein fragments (covalently linked three heavy atoms) with interatomic distance ≤5 Å. The interaction pairs were grouped into ligand atoms with the same SYBYL atom type surrounding each type of protein fragment, which were further clustered via Bayesian Gaussian Mixture Model (BGMM). Gaussian distributions with ligand atoms ≥20 were identified as significant interaction patterns. Reliability of the significant interaction patterns was validated by comparing the difference of number of significant interaction patterns between the docked poses with higher and lower similarity to the native crystal structures. Fifty-one candidate targets of brucine, strychnine and icajine involved in Semen Strychni (Mǎ Qián Zǐ) and eight candidate targets of astragaloside-IV, formononetin and calycosin-7-glucoside involved in Astragalus (Huáng Qí) were predicted by the significant interaction patterns, in combination with docking, which were consistent with the therapeutic effects of Semen Strychni and Astragalus for cancer and chronic pain. The new strategy in this study improves the accuracy of target identification for small molecules, which will facilitate discovery of botanical drugs.

11.
J Am Chem Soc ; 143(38): 15599-15605, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34533943

RESUMO

An electrochemical asymmetric coupling of secondary acyclic amines with ketones via a Shono-type oxidation has been described, affording the corresponding amino acid derivatives with good to excellent diastereoselectivity and enantioselectivity. The addition of an N-oxyl radical as a redox mediator could selectively oxidize the substrate rather than the product, although their oxidation potential difference is subtle (about 13 mV). This electrochemical transformation proceeds in the absence of stoichiometric additives, including metals, oxidants, and electrolytes, which gives it good functional group compatibility. Mechanistic studies suggest that proton-mediated racemization of the product is prevented by the reduction of protons at the cathode.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34567206

RESUMO

Astragalus membranaceus has complex components as a natural drug and has multilevel, multitarget, and multichannel effects on dilated cardiomyopathy (DCM). However, the immune mechanism, gene module, and molecular subtype of astragalus membranaceus in the treatment of DCM are still not revealed. Microarray information of GSE84796 was downloaded from the GEO database, including RNA sequencing data of seven normal cardiac tissues and ten DCM cardiac tissues. A total of 4029 DCM differentially expressed genes were obtained, including 1855 upregulated genes and 2174 downregulated genes. GO/KEGG/GSEA analysis suggested that the activation of T cells and B cells was the primary cause of DCM. WGCNA was used to obtain blue module genes. The blue module genes are primarily ADCY7, BANK1, CD1E, CD19, CD38, CD300LF, CLEC4E, FLT3, GPR18, HCAR3, IRF4, LAMP3, MRC1, SYK, and TLR8, which successfully divided DCM into three molecular subtypes. Based on the CIBERSORT algorithm, the immune infiltration profile of DCM was analyzed. Many immune cell subtypes, including the abovementioned immune cells, showed different levels of increased infiltration in the myocardial tissue of DCM. However, this infiltration pattern was not obviously correlated with clinical characteristics, such as age, EF, and sex. Based on network pharmacology and ClueGO, 20 active components of Astragalus membranaceus and 40 components of DMCTGS were obtained from TCMSP. Through analysis of the immune regulatory network, we found that Astragalus membranaceus effectively regulates the activation of immune cells, such as B cells and T cells, cytokine secretion, and other processes and can intervene in DCM at multiple components, targets, and levels. The above mechanisms were verified by molecular docking results, which confirmed that AKT1, VEGFA, MMP9, and RELA are promising potential targets of DCM.

13.
Arthritis Res Ther ; 23(1): 250, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587995

RESUMO

OBJECTIVE: Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of patients with primary Sjögren's syndrome and to correlate these findings with their disease activity. METHODS: Fifty-two patients with primary SS and 52 sex- and age-matched healthy control subjects were included. All of them underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerized testing including the three stages of smell: threshold, identification, and memory of the different odors. RESULTS: All the olfactory scores (olfactory threshold, identification, and memory) in patients with pSS were significantly decreased than the control group (all P < 0.01). Patients had higher proportion of anosmia (13.5% vs 0%) and hyposmia (19.2% vs 11.5%) than controls (χ2 = 10.526, P < 0.01). Multivariable regression analysis revealed that ESSDAI and the symptoms of dryness, fatigue, and limb pain had negative influence on olfactory function (adjusted R2 = 0.381, 0.387, 0.513, and 0.614, respectively). ESSPRI showed significantly negative association with olfactory threshold, identification, memory, and total scores. Olfactory identification and memory scores were decreased in pSS patients with thyroid dysfunction or hypocomplementemia (P < 0.05). Smell threshold scores were decreased in pSS patients with anti-SSA antibody or anti-nuclear antibody compared with those without those autoantibodies (P < 0.01). CONCLUSION: Our findings indicate that olfactory functions are impaired in pSS patients. There was a close correlation between olfactory dysfunction and disease severity and immunological abnormalities. Immune and systemic inflammation dysregulation might play a role in the mechanism of this defect.


Assuntos
Transtornos do Olfato , Síndrome de Sjogren , Fadiga , Humanos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Dor , Índice de Gravidade de Doença , Síndrome de Sjogren/complicações
14.
J Microbiol ; 59(10): 931-940, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34554454

RESUMO

C-Glycosides are an important type of natural product with significant bioactivities, and the C-glycosidic bonds of C-glycosides can be cleaved by several intestinal bacteria, as exemplified by the human faeces-derived puerarin-degrading bacterium Dorea strain PUE. However, glycoside hydrolases in these bacteria, which may be involved in the C-glycosidic bond cleavage of C-glycosides, remain largely unknown. In this study, the genomes of the closest phylogenetic neighbours of five puerarin-degrading intestinal bacteria (including Dorea strain PUE) were retrieved, and the protein-coding genes in the genomes were subjected to sequence similarity network (SSN) analysis. Only four clusters of genes were annotated as glycoside hydrolases and observed in the genome of D. longicatena DSM 13814T (the closest phylogenetic neighbour of Dorea strain PUE); therefore, genes from D. longicatena DSM 13814T belonging to these clusters were selected to overexpress recombinant proteins (CG1, CG2, CG3, and CG4) in Escherichia coli BL21(DE3). In vitro assays indicated that CG4 efficiently cleaved the O-glycosidic bond of daidzin and showed moderate ß-D-glucosidase and ß-D-xylosidase activity. CG2 showed weak activity in hydrolyzing daidzin and pNP-ß-D-fucopyranoside, while CG3 was identified as a highly selective and efficient α-glycosidase. Interestingly, CG3 and CG4 could be selectively inhibited by daidzein, explaining their different performance in kinetic studies. Molecular docking studies predicted the molecular determinants of CG2, CG3, and CG4 in substrate selectivity and inhibition propensity. The present study identified three novel and distinctive glycoside hydrolases, highlighting the potential of SSN in the discovery of novel enzymes from genomic data.

15.
Ann Rheum Dis ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556485

RESUMO

OBJECTIVES: We previously identified a hypomorphic variant, p.Arg90His (p.R90H) of neutrophil cytosolic factor 1 (NCF1, a regulatory subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 complex), as an putative causal variant for systemic lupus erythematosus (SLE), and established a knock-in (KI) H90 variant in the C57BL/6 background to study how this variant promotes lupus development. METHODS: Wild type (WT) and KI littermates were assessed for immune profiles and lupus-like features. Disease activity and renal damage of patients with SLE were assessed by systemic lupus erythematosus disease activity index (SLEDAI) and renal items of systemic lupus international collaborating clinics (SLICC), respectively. RESULTS: Compared with WT littermates, 5-week-old homozygous KI mice had reduced oxidative burst, splenomegaly, elevated type I interferon (IFN-I) scores, increased ratios of splenic follicular T helper 2 (Tfh2) to either T follicular regulatory (Tfr) or Tfh1 cells, increased ANA+ follicular, germinal centre and plasma cells without spontaneous kidney disease up to 1 year of age. Pristane treatment exacerbated the immune dysregulation and induced IFN-I-dependent kidney disease in 36-week-old H90 KI female mice. Decreased efferocytosis of macrophages derived from KI mice and patients with homozygous H90 SLE promoted elevated ratios of Tfh2/Tfr and Tfh2/Tfh1 as well as dysregulated humoral responses due to reduced voltage-gated proton channel 1 (Hv1)-dependent acidification of phagosome pH to neutralise the decreased electrogenic effect of the H90 variant, resulting in impaired maturation and phagosome proteolysis, and increased autoantibody production and kidney damage in mice and patients with SLE of multiple ancestries. CONCLUSIONS: A lupus causal variant, NCF1-H90, reduces macrophage efferocytosis, enhances Tfh2 responses and promotes autoantibody production and kidney damage in both mice and patients with SLE.

16.
Environ Microbiol ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34490968

RESUMO

Bacterial secondary metabolites are rich sources of novel drug leads. The diversity of secondary metabolite biosynthetic gene clusters (BGCs) in genome-sequenced bacteria, which will provide crucial information for the efficient discovery of novel natural products, has not been systematically investigated. Here, the distribution and genetic diversity of BGCs in 10 121 prokaryotic genomes (across 68 phyla) were obtained from their PRISM4 outputs using a custom python script. A total of 18 043 BGCs are detected from 5743 genomes with non-ribosomal peptide synthetases (25.4%) and polyketides (15.9%) as the dominant classes of BGCs. Bacterial strains harbouring the largest number of BGCs are revealed and BGC count in strains of some genera vary greatly, suggesting the necessity of individually evaluating the secondary metabolism potential. Additional analysis against 102 strains of discovered bacterial genera with abundant amounts of BGCs confirms that Kutzneria, Kibdelosporangium, Moorea, Saccharothrix, Cystobacter, Archangium, Actinosynnema, Kitasatospora, and Nocardia, may also be important sources of natural products and worthy of priority investigation. Comparative analysis of BGCs within these genera indicates the great diversity and novelty of the BGCs. This study presents an atlas of bacterial secondary metabolite BGCs that provides a lot of key information for the targeted discovery of novel natural products.

17.
Nano Lett ; 21(19): 8151-8159, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34586821

RESUMO

Differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into functional neural cells has been widely investigated for treating neural diseases. However, the limited neural differentiation of BMSCs remains a big challenge to overcome. Herein, for the first time, ginseng-derived exosomes (G-Exos) were demonstrated to have excellent efficiency in stimulating the neural differentiation of BMSCs by transferring the incorporated miRNAs to BMSCs efficiently. In vivo, a photo-cross-linkable hydrogel with chemokine and G-Exos loaded shows strong efficacy in recruiting and directing the neural differentiation of BMSCs in the program. G-Exos were demonstrated to be promising nanoplatforms in transferring plant-derived miRNAs to mammalian stem cells for neural differentiation both in vitro and in vivo, possessing great potential in neural regenerative medicine.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Animais , Diferenciação Celular , Hidrogéis , MicroRNAs/genética
19.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3873-3876, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472262

RESUMO

Compounds(1-6) were isolated and identified from 90% ethanol extract of the stems and leaves of Cassia occidentalis through column chromatography with silica gel, ODS, and Sephadex LH-20. These compounds were identified as 7-hydroxy-5-(3-hydroxy-2-oxopropyl)-2-methyl-4H-chromen-4-one(1), saccharonol A(2), S-6-hydroxymullein(3), 2-methyl-5-acetonyl-7-hydroxy-chromone(4), 2-(2'-hydroxypropyl)-5-methyl-7-hydroxychromone(5) and 7,4'-dihydroxyflavone(6) based on their physicochemical and spectroscopic data. Among them, compound 1 was a new compound, and all the compounds were isolated from this plant for the first time. DPPH method was employed to determine the antioxidant activities of these compounds in vitro. Six compounds exhibited weak antioxidant activities.


Assuntos
Senna (Planta) , Cromonas , Folhas de Planta , Análise Espectral
20.
Cell Death Differ ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34511601

RESUMO

Gasdermin-D (GSDMD), the executioner of pyroptotic cell death when it is cleaved by inflammatory caspases, plays a crucial role in host defense and the response to danger signals. So far, there are no known mechanisms, other than cleavage, for regulating GSDMD. Here, we show that tripartite motif protein TRIM21 acts as a positive regulator of GSDMD-dependent pyroptosis. TRIM21 interacted with GSDMD via its PRY-SPRY domain, maintaining GSDMD stable expression in resting cells yet inducing the N-terminus of GSDMD (GSDMD-N) aggregation during pyroptosis. TRIM21-deficient cells displayed a reduced cell death in response to NLRP3 or NLRC4 inflammasome activation. Genetic ablation of TRIM21 in mice conferred protection from LPS-induced inflammation and dextran sulfate sodium-induced colitis. Therefore, TRIM21 plays an essential role in GSDMD-mediated pyroptosis and may be a viable target for controlling and treating inflammation-associated diseases.

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