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1.
Ultrasound Med Biol ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34593278

RESUMO

This study sought to investigate the feasibility of using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) fusion imaging navigation (FIN) with needle tail intelligent positioning (NTIP) to guide puncture in percutaneous transforaminal endoscopic discectomy (PTED). First, in a pig experiment, we found that puncture errors in lumbar intervertebral foramen (LIF) puncture using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) FIN with NTIP for experienced and novice operators were 2.00 ± 1.00 and 2.57 ± 0.98 mm, respectively (p = 0.231), suggesting this technique was minimally dependent on experience. Then, two experienced surgeons agreed (inter-observer agreement к=0.801) that the quality of MR-MR fusion images was good or sufficient. Finally, we performed PTED in eight patients using MR-MR-US FIN with NTIP, and no significant complications were reported during LIF puncture. Overall, MR-MR-US FIN with NTIP may be a potential application for guiding puncture in PTED, but more clinical studies with a larger sample size are required to further evaluate the advantages of MR-MR-US FIN with NTIP.

2.
Eur Radiol ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665315

RESUMO

OBJECTIVE: To explore whether radiomics features extracted from pre-treatment magnetic resonance imaging (MRI) can predict the overall survival (OS) in patients with hypopharyngeal squamous cell carcinoma. METHODS: A total of 190 patients with hypopharyngeal squamous cell carcinoma were eligibly enrolled from two institutions. Radiomics features were extracted from contrast-enhanced axial T1-weighted (CE-T1WI) sequence. The least absolute shrinkage selection operator (LASSO) algorithm was applied to establish a radiomics score correlated with OS. Multivariate logistic regression analysis was applied to determine the independent risk factors, which was combined with radiomics score to build the final radiomics nomogram. RESULTS: A radiomics score with 6 CE-T1WI features for OS prediction was constructed and validated; its integration with specific clinicopathologic factors (N stage) showed a better prediction performance in the training, internal validation, and external validation cohorts (C-index 0.78, 0.75, and 0.75). Calibration curves determined a good agreement between the predicted and actual overall survival. CONCLUSIONS: The radiomics-clinical nomogram and radiomics score might be non-invasive and reliable methods for the risk stratification in patients with hypopharyngeal squamous cell carcinoma. KEY POINTS: • An MRI-based radiomics model was constructed to evaluate of OS in patients with hypopharyngeal squamous cell carcinoma. • A radiomics-clinical nomogram that combined radiomics features and clinical characteristics was established. • Multi-cohort study validated the predictive performance of the radiomics-clinical nomogram to stratify patients with high risk in clinical practice.

4.
Nanoscale ; 13(37): 15699-15710, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34529746

RESUMO

Although efforts have been devoted to develop new antibacterial agents and techniques, the challenge of bacterial infection remains unresolved and is even increasing. Sonodynamic therapy (SDT) driven by ultrasound (US) has demonstrated effectiveness in terms of penetration and it can help to clinically address the problem of deep tissue bacterial infection. In recent years, a variety of sonosensitizers, which were originally designed for photodynamic therapy, have been adopted for SDT. Yet, their unstable chemical stability and ineffective electron-hole separation are not favorable for clinical applications. Hence, we designed a new type of antibacterial sonosensitizer-namely, Au@Cu2O hybrid nanocubes-in which an interfacial Schottky junction was built between a p-type semiconductor Cu2O and a noble metal Au. When US stimulation was applied, the electrons from Cu2O could be excited at the junction and transferred to Au. Since the formed Schottky barrier could block the backflow of US-excited electrons, a prolonged electron-hole separation can be successfully established. Additionally, because of the boosted sonocatalytic activity, the Au@Cu2O hybrid nanocubes could produce a large amount of reactive oxygen species (ROS), which are subject to US stimulation. Furthermore, we found that the sonocatalytic activity of the Au@Cu2O hybrid nanocubes could be reinforced by increasing the amount of Au, enabling 99.67% of Staphylococcus aureus (S. aureus) to be killed by US stimulation for 15 minutes. The cytocompatibility of Au@Cu2O hybrid nanocubes was improved by a red blood cell membrane (RBC) coating over the surface, and the membrane did not sacrifice its superior antibacterial properties.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Antibacterianos/farmacologia , Humanos , Espécies Reativas de Oxigênio
5.
J Am Chem Soc ; 143(37): 15427-15439, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34516125

RESUMO

Traditional surgical intervention and antibiotic treatment are poor and even invalid for chronic diseases including periodontitis induced by diverse oral pathogens, which often causes progressive destruction of tissues, even tooth loss, and systemic diseases. Herein, an ointment comprising atomic-layer Fe2O3-modified two-dimensional porphyrinic metal-organic framework (2D MOF) nanosheets is designed by incorporating a polyethylene glycol matrix. After the atomic layer deposition surface engineering, the enhanced photocatalytic activity of the 2D MOF heterointerface results from lower adsorption energy and more charge transfer amounts due to the synergistic effect of metal-linker bridging units, abundant active sites, and an excellent light-harvesting network. This biocompatible and biodegradable 2D MOF-based heterostructure exhibits broad-spectrum antimicrobial activity (99.87 ± 0.09%, 99.57 ± 0.21%, and 99.03 ± 0.24%) against diverse oral pathogens (Porphyromonas gingivalis, Fusobacterium nucleatum, and Staphylococcus aureus) by the synergistic effect of reactive oxygen species and released ions. This photodynamic ion therapy exhibits a superior therapeutic effect to the reported clinical periodontitis treatment owing to rapid antibacterial activity, alleviative inflammation, and improved angiogenesis.

7.
Head Neck ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34516714

RESUMO

BACKGROUND: To establish a radiomics nomogram for survival prediction and determine if genomic data were related to radiomics signature in advanced nasopharyngeal carcinoma (NPC). METHODS: Radiomics features were extracted from contrast-enhanced T1-weighted images (CE-T1WI) in 316 patients. A progression-free survival (PFS) nomogram was developed and validated by the combination of the radiomics signature and clinicopathologic factors. Whole transcriptomics sequencing was performed in pretreatment tumor samples; correlation of gene expression and radiomics signature was further investigated. RESULTS: A 24-feature-combined radiomics signature was highly correlated with PFS; its integration with clinical predictors showed good prediction performance in the training and the validation cohort (C-index: 0.80 and 0.73). A significant correlation was observed between certain gene expression and Rad-score, especially the mRNA expression of CDKL2, PLIN5, and SPAG1. CONCLUSION: As a noninvasive method, the MRI-based radiomics signature might enable the pretreatment prediction of prognosis and gene expressions profile in advanced NPC.

8.
Front Med (Lausanne) ; 8: 712324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490301

RESUMO

Hepatic hemangioma (HH) is a congenital vascular anomaly comprising networks of abnormal blood and/or lymphatic vessels with endothelial cell proliferation. Their pathophysiology is not fully understood, and no specific drug is available to treat them. Conservative management, which limits observation, is preferred for most patients. A HH larger than 4 cm is considered a giant HH that may be treated using surgery ranging from embolization to hepatic resection or liver transplantation. Here, we describe a case with multiple and giant HHs that regressed significantly after treatment with azithromycin (AZM). A systematic literature review of HH and the effects of AZM on angiogenesis was then conducted.

9.
Clin Spine Surg ; 34(7): E382-E389, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397532

RESUMO

STUDY DESIGN: This was a cross-sectional study. OBJECTIVE: The objective of this study was to assess cervical paravertebral extensor degeneration in patients with cervical spondylotic myelopathy (CSM) and its impact on the sagittal parameters and functional status of the cervical spine. SUMMARY OF BACKGROUND DATA: Paravertebral extensor degeneration is well-studied in CSM; however, the effect of extensor degeneration on the sagittal balance and functional status of the cervical spine is unclear. MATERIALS AND METHODS: We enrolled 52 CSM patients (CSM group) and 52 age-matched and sex-matched healthy adults (control group). The C2-C7 and C0-C2 Cobb angles (CAs), C7 slope, T1 slope, cervical arc cord distance, cervical tilt (CERT), cranial tilt (CRAT), and C2-C7 sagittal vertical axis (SVA) were measured. The cross-sectional areas of the deep extensors (DEA), superficial extensors (SEA), and cervical vertebral body (VBA) of C4-C7 were measured. DEA/VBA and SEA/VBA were used to quantify the extensor volume. We analyzed the fatty infiltration ratio of the deep (DFIR) and superficial extensors (SFIR). The Visual Analog Scale, Neck Disability Index, and modified Japanese Orthopaedic Association Scale scores of the CSM group were calculated. RESULTS: The DEA/VBA was significantly lower and the DFIR and SFIR were significantly higher in the CSM group. The C4 DEA/VBA correlated with the C2-C7 SVA, C2-C7 CA, CERT, and the Neck Disability Index and modified Japanese Orthopaedic Association Scale scores (r=-0.608, 0.291, 0.335,-0.649, and 0.409, respectively). The DEA/VBA of C5 correlated with the cervical arc cord distance and CRAT (r=-0.350 and -0.356, respectively). The C4 DFIR correlated with the C2-C7 SVA, C2-C7 CA, and the Visual Analog Scale (r=0.286, -0.297, and 0.429, respectively). The SFIR of C7 correlated with the T1 slope and C7 slope (r=0.368 and 0.319, respectively). CONCLUSIONS: Paravertebral extensor degeneration negatively impacts the sagittal sequence and functional status of the cervical spine in CSM patients. Our study provides an insight into understanding the significance of cervical muscular degeneration in CSM patients. LEVEL OF EVIDENCE: Level III.

10.
ACS Appl Mater Interfaces ; 13(36): 42554-42563, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34464099

RESUMO

Residual Li and oxygen vacancies in Ni-rich cathode materials have a great influence on electrochemical performance, yet their role is still poorly understood. Herein, by simply adjusting the oxygen flow during the high-temperature sintering process, some Li2O can be carried into the exhaust gas and the contents of residual Li and oxygen vacancies in LiNi0.825Co0.115Mn0.06O2 cathodes can be accurately controlled. Residual Li reduces the surficial Li+ diffusion coefficient, thereby limiting the rate property of the cathode. Oxygen vacancies affect the oxygen release energy in the crystal, and the lowest oxygen release energy is found at an oxygen vacancy concentration of 8.35%, resulting in an unstable structure and thereby poor cycle performance. The Ni-rich cathode with low residual Li and oxygen vacancy contents exhibits superior capacity retention (89.55 and 77.66%) at 2C after 300 cycles between 2.7-4.3 and 2.7-4.5 V. These findings clarify the role of residual Li and oxygen vacancies in Ni-rich cathode materials and provide a simple way to obtain high-performance Ni-rich cathodes for high-energy-density Li-ion batteries.

11.
J Phys Condens Matter ; 33(46)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34425563

RESUMO

The asymmetrical long-range hopping amplitudes have a rich influence on the topological properties. Here, a non-Hermitian model including the long-range hopping amplitudes is constructed to explore those properties. It can be found that an extra topological invariantW= 2 emerges as a consequence of the long-range hopping amplitudes. Furthermore, we find that the phaseW= 2 can be directly characterized by the generalized Brillouin zone (GBZ) itself through the concept of the argument principle. Meanwhile, a gapless phase dubbed as topological semimetal phase can be induced by the asymmetrical long-range hopping. Moreover, the physical origin of the topological semimetal phase can be explained by the solutions of eigen-equation. It is also shown that the skin modes exist as long as the GBZ and the Brillouin zone differ from each other. These interesting phases may be realized in an electrical-circuit simulator.

12.
iScience ; 24(8): 102837, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34368653

RESUMO

A number of new cell death processes have been discovered in recent years, including ferroptosis, which is characterized by the accumulation of lipid peroxidation products derived from iron metabolism. The evidence suggests that ferroptosis has a tumor-suppressor function. However, the mechanism by which ferroptosis mediates the response of tumor cells to oncolytic viruses remains poorly understood. The Newcastle disease virus (NDV) can selectively replicate in tumor cells. We show that NDV-induced ferroptosis acts through p53-SLC7A11-GPX4 pathway. Meanwhile, the levels of intracellular reactive oxygen species and lipid peroxides increased in tumor cells. Ferritinophagy was induced by NDV promotion of ferroptosis through the release of ferrous iron and an enhanced Fenton reaction. Collectively, these observations demonstrated that the NDV can kill tumor cells through ferroptosis. Our study provides novel insights into the mechanisms of NDV-induced ferroptosis and highlights the critical role of viruses in treating therapy-resistant cancers.

13.
Int J Mol Sci ; 22(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299017

RESUMO

Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography-mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided.


Assuntos
Hipóxia Celular , Cromatografia de Fase Reversa/métodos , Células Epiteliais/metabolismo , Túbulos Renais Proximais/metabolismo , Metabolômica/métodos , Espectrometria de Massas em Tandem/métodos , Ativação Metabólica/genética , Ativação Metabólica/fisiologia , Hipóxia Celular/genética , Linhagem Celular , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Técnicas In Vitro , Rim/citologia , Rim/metabolismo , Rim/patologia , Metaboloma/genética , Análise Multivariada , Análise de Componente Principal
14.
Oncogene ; 40(37): 5639-5650, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34321604

RESUMO

Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

15.
Poult Sci ; 100(8): 101267, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34237546

RESUMO

The genotype VII Newcastle disease virus (NDV) vaccine has begun to replace the traditional genotype II NDV vaccine and is widely used in the commercial poultry of China. However, the effect of homologous and heterogeneous anti-NDV serum on the evolution of prevalent NDV is unknown. To understand the effect of genotype II and VII anti-NDV serum on the evolution of genotype VII NDV strains, ZJ1 (waterfowl origin) and CH/SD/2008/128 (ND128; chicken origin) were used for serial passage of 30 generations in DF-1 cells without anti-NDV serum or with genotype II and VII anti-NDV serum independently. The F and HN genes of the 2 viruses were amplified for the 10th, 20th, and 30th generations of each serial passage group and compared with their respective original viruses. We found that there was only one mutation at position 248 in the F gene of ZJ1 due to the serum pressure of genotype VII anti-NDV. Similarly, mutations at residue 527 of the F gene, and position 9 and 319 of the HN gene of ND128 were noted in both anti-NDV serum groups. The results show that the nonsynonymous (NS)-to-synonymous (S) ratio of the F gene of ZJ1 virus was 1.6, and for the HN gene, it was 2.5 in the anti-II serum group. In the anti-VII serum group, the NS/S ratio for the F gene was 2.1, and for the HN gene, it was 2.5. The NS/S ratio of the F gene of the ND128 virus was 0.8, and for the HN gene, it was 3 in the anti-II serum group. Furthermore, the NS/S ratio of the F gene was 0.8, and the HN gene was 2.3 in the anti-VII group. Taken together, our findings highlight that there was no significant difference in the variation of protective antigens in genotype VII NDV under the selection pressure of homologous and heterogeneous genotype NDV inactivated vaccines.


Assuntos
Doença de Newcastle , Doenças das Aves Domésticas , Vacinas Virais , Animais , Galinhas , China , Genótipo , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/genética , Doenças das Aves Domésticas/prevenção & controle
16.
J Clin Ultrasound ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240426

RESUMO

Acute transient swelling (ATS) of the thyroid is a rare complication following fine-needle aspiration (FNA) of thyroid nodules. We present 31 cases with 35 nodules encountered at our institute and reported in the literature, to provide further information. The incidence rate in our institute was 0.46%. Of these nodules, 74.3% (26/35) were solid, 65.7% (23/35) exhibited hypervascularity, and 77.2% (27/35) were benign or follicular neoplasms. Although most cases (87.1%, 27/31) occurred within 2 h after FNA, four patients experienced delayed ATS after 7 h to 2 days. Therefore, awareness of this complication, especially its delayed occurrence, should be raised.

17.
Int J Hyperthermia ; 38(1): 1060-1068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34265235

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) has been recommended as the treatment for benign thyroid nodules (BTNs) by some guidelines. However, detailed follow-up instructions for thyroid function about the timing and affected populations after RFA are lacked due to insufficient researches. This 12-month prospective study aimed to evaluate the incidence and risk factors of thyroid dysfunction at different time points after RFA, especially within 1 week that previous studies didn't concern. METHODS: Seventy-five euthyroid patients who underwent RFA for symptomatic BTNs were enrolled (ChiCTR-INR-16007884). The incidence of thyroid dysfunction within 1 week, at 1, 6, and 12 months after RFA was evaluated. The risk factors for different types of thyroid dysfunction in the different terms were further analyzed. RESULTS: Within 1 week after RFA, the incidence of thyroid dysfunction was as high as 36.00% unexpectedly, and only overt thyrotoxicosis and subclinical thyrotoxicosis occurred, which were significantly associated with the low-normal baseline thyrotropin (TSH) level (p = 0.001) and high ablation volume ratio (p = 0.008). From 1 to 12 months (the long term), the incidence dropped significantly and remained low (8.00-12.00%); and thyroid dysfunction presented as overt thyrotoxicosis, subclinical thyrotoxicosis, and subclinical hypothyroidism. The long-term thyrotoxicosis group had more cases with diabetes and lower baseline TSH levels. The long-term subclinical hypothyroidism group had more cases with positive thyroid peroxidase antibodies, higher baseline TSH levels, and higher ablation volume ratios. CONCLUSIONS: After the RFA of BTNs, thyroid dysfunction was more likely to occur within 1 week and in populations with risk factors.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Ablação por Cateter/efeitos adversos , Humanos , Estudos Prospectivos , Ablação por Radiofrequência/efeitos adversos , Fatores de Risco , Nódulo da Glândula Tireoide/cirurgia , Resultado do Tratamento
18.
BMC Musculoskelet Disord ; 22(1): 545, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126979

RESUMO

BACKGROUND: Acute compartment syndrome (ACS) is a potentially devastating condition. ACS is rare in the upper arm. CASE PRESENTATION: We report a case of acute compartment syndrome of the anterior compartment of the upper arm due to brachial muscle injury. The patient experienced abnormal progressive swelling and pain in his right upper arm, and passive pulling pain of the right wrist and right hand. It was highly suspected to be right upper arm compartment syndrome, and was confirmed by surgery. The patient transferred to the emergency operating room for fasciotomy that was performed under general anesthesia using the anterolateral approach. The brachial muscle was found to be heavily swollen and had the greatest tension. The brachial muscle fibers were split lengthwise, and a large amount of hematoma was cleared. The brachial muscles were injured and partly ruptured. After full decompression, a negative pressure drainage device was used to cover the wound in the first stage. Ten days after injury, the swelling of the affected limb subsided and the wound was sutured. The patient's limbs completely recovered to normal. The shoulder and elbow joints could move freely and the patient resumed normal farming work ability. CONCLUSION: Clinicians should fully recognize the fact that acute compartment syndrome can occur in the upper arm, rather than only the forearm and leg, and therefore avoid serious consequences caused by missed diagnosis and misdiagnosis.


Assuntos
Braço , Síndromes Compartimentais , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/etiologia , Síndromes Compartimentais/cirurgia , Fasciotomia , Antebraço , Humanos , Músculos
19.
Wideochir Inne Tech Maloinwazyjne ; 16(2): 329-335, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34136028

RESUMO

Introduction: The influence of anesthetic method on the immune function and oxidative stress in patients receiving laparoscopic herniorrhaphy remains largely unknown. Aim: To assess the effects of different anesthetic methods on the immune function and oxidative stress in patients undergoing laparoscopic herniorrhaphy. Material and methods: A total of 280 eligible patients were randomly divided into two groups to receive total intravenous anesthesia (TIVA group) and inhalation anesthesia (IA group). T lymphocyte subsets, oxidative stress response indices and inflammatory factor levels were measured before anesthesia, at the end of the operation, and 1 and 3 days after the operation. The incidence rates of adverse reactions were compared. Results: At the end of and 1 day after the operation, CD3+ and CD4+ T cells and CD4+/CD8+ decreased in both groups compared with those before anesthesia (p < 0.05). Three days after the operation, CD3+ and CD4+ T cells decreased in both groups compared with those before anesthesia, which were higher in the TIVA group (p < 0.05). Interleukin-6 and C-reactive protein levels were significantly lower in the TIVA group (p < 0.05). At the end of and 1 and 3 days after the operation, oxidative stress response indices superoxide dismutase, catalase and glutathione peroxidase declined in both groups compared with those before anesthesia, which were higher in the IA group (p < 0.05). The incidence rate of adverse reactions was significantly higher in the IA group (p = 0.002). Conclusions: Compared with IA, TIVA has less effect on the immune function and oxidative stress of patients undergoing laparoscopic herniorrhaphy, and controls the inflammatory response more effectively, accompanied by a lower incidence rate of adverse reactions.

20.
mBio ; 12(3): e0100521, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34125604

RESUMO

DEAD (Glu-Asp-Ala-Glu) box RNA helicases have been proven to contribute to antiviral innate immunity. The DDX21 RNA helicase was identified as a nuclear protein involved in rRNA processing and RNA unwinding. DDX21 was also proven to be the scaffold protein in the complex of DDX1-DDX21-DHX36, which senses double-strand RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes caspase-dependent cleavage after virus infection and treatment with RNA/DNA ligands, especially for RNA virus and ligands. Caspase-3/6 cleaves DDX21 at D126 and promotes its translocation from the nucleus to the cytoplasm in response to virus infection. The cytoplasmic cleaved DDX21 negatively regulates the interferon beta (IFN-ß) signaling pathway by suppressing the formation of the DDX1-DDX21-DHX36 complex. Thus, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immune response to virus. IMPORTANCE Innate immunity serves as the first barrier against virus infection. DEAD (Glu-Asp-Ala-Glu) box RNA helicases, originally considered to be involved in RNA processing and RNA unwinding, have been shown to play an important role in antiviral innate immunity. The precise regulation of innate immunity is critical for the host because the aberrant production of cytokines leads to unexpected pathological consequences. Here, we identified that DDX21 was cleaved at D126 by virus infection and treatment with RNA/DNA ligands via the caspase-3/6-dependent pathway. The cytoplasmic cleaved DDX21 negatively regulates the IFN-ß signaling pathway by suppressing the formation of the DDX1-DDX21-DHX36 complex. In sum, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immune response to virus.

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