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1.
Bioinformatics ; 39(4)2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37018146

RESUMEN

SUMMARY: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs. AVAILABILITY AND IMPLEMENTATION: eccDB is freely available at http://www.xiejjlab.bio/eccDB.


Asunto(s)
Cromatina , ADN Circular , Cromatina/genética , Cromosomas , ADN , Secuencia de Bases
2.
BMC Med Educ ; 24(1): 201, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413978

RESUMEN

BACKGROUND: To explore the feasibility and effectiveness of applying CBL teaching method and SEGUE Framework in the doctor-patient communication skills of resident physicians in the department of otolaryngology. METHODS: This is an observational study to compare the score changes in doctor-patient communication skills of 120 resident physicians, before and after using CBL combined SEGUE Framework teaching method. The effects of gender, age, grade, educational background and marital status on SEGUE score were analyzed. RESULTS: Through the combined application of CBL teaching method and SEGUE Framework, the SEGUE score of 120 resident physicians was significantly improved. There was no significant difference in SEGUE score among different sex and marital status of resident physicians. SEGUE score is positively correlated with age; Different grades and educational backgrounds have significant effects on SEGUE score. CONCLUSION: The combination of CBL teaching method and SEGUE Framework is feasible and effective in the education program of doctor-patient communication skills for resident physicians in the department of otolaryngology, and worthy of popularization and application in other medical specialties.


Asunto(s)
Internado y Residencia , Otolaringología , Médicos , Humanos , Competencia Clínica , Comunicación , Otolaringología/educación , Enseñanza , Estudios de Factibilidad
3.
Med Sci Monit ; 29: e940337, 2023 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-37480226

RESUMEN

BACKGROUND We explored a new method for measuring the length of artificial stapes during stapedotomy in otoendoscopic middle-ear surgery using a flexible ruler. MATERIAL AND METHODS A retrospective analysis was conducted on 56 cases of otosclerosis, comprising 56 ears with a follow-up of over 6 months and complete data. Patients were admitted to the Department of Otology, Huazhong University of Science and Technology Union Shenzhen Hospital from July 2020 to June 2022. SPSS statistical software was used for efficacy analysis. The results of different measurement methods on the implantation time of the prosthesis and postoperative hearing follow-up were compared. RESULTS The 56 patients were randomly divided into 2 groups. In 1 case measured by the metal measuring stick, the prosthesis was too short and was replaced during the operation; 2 patients experienced transient dizziness postoperatively, and the other patients had no surgical complications. All 56 patients had varying degrees of hearing improvement after surgery, and no dislocation of the ossicular chain was observed during the follow-up. There was a statistically significant difference in the implantation time of the prosthesis between the different measurement methods (P<0.05). The improvement in hearing in the flexible ruler group was statistically significant (P<0.05). CONCLUSIONS The selection of the length of the ossicular prosthesis is a crucial step in the operation and can directly affect hearing outcomes. The use of a flexible ruler to measure prosthesis length can significantly shorten operation time and improve hearing, and the ruler is easily obtainable. It is worth promoting its application in ear endoscopic stapedotomy.


Asunto(s)
Miembros Artificiales , Prótesis Osicular , Humanos , Estribo , Estudios Retrospectivos , Implantación de Prótesis
4.
Molecules ; 28(12)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37375148

RESUMEN

MOF-based luminescent sensors have garnered considerable attention due to their potential in recognition and discrimination with high sensitivity, selectivity, and fast response in the last decades. Herein, this work describes the bulk preparation of a novel luminescent homochiral MOF, namely, [Cd(s-L)](NO3)2 (MOF-1), from an enantiopure pyridyl-functionalized ligand with rigid binaphthol skeleton under mild synthetic condition. Except for the features of porosity and crystallinity, the MOF-1 has also been characterized with water-stability, luminescence, and homochirality. Most important, the MOF-1 exhibits highly sensitive molecular recognition toward the4-nitrobenzoic acid (NBC) and moderate enantioselective detection of proline, arginine, and 1-phenylethanol.

5.
Nanotechnology ; 33(21)2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35147518

RESUMEN

To improve the sensitivity for electro-chemiluminescent (ECL) detection of chloramphenicol (CAP), a common broad-spectrum antibiotic, boron nitride quantum dots (BNQDs) were prepared with excellent photoelectric property and low toxicity. After its structure and electrochemical property were investigated in detail, it was noted that the ECL signal of Ru(Phen)32+could be strengthened by the proposed BNQDs, which was further activated by ten's times in the presence of CAP. Under the optimized conditions, there was an excellent linear relationship between ΔECL and lgcCAPin a wide linear range from 1.0 × 10-10to 1.0 × 10-6mol l-1CAP. The detection limit was super-low to be 3.3 × 10-11mol l-1(S/N = 3). When applied for CAP detection in real pharmaceutical and food samples, the recoveries were between 97.8% and 105.7% with R.S.D. less than 3.3%. A possible CAP-activated ECL mechanism of BNQDs-Ru(phen)32+was also proposed. This work will offer a great potential for efficient monitoring of CAP pollution and clinical diagnosing of CAP-related diseases in future.

6.
Nanotechnology ; 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35144249

RESUMEN

To improve the sensitivity for electro-chemiluminescent (ECL) detection of chloramphenicol (CAP), a common broad-spectrum antibiotic, boron nitride quantum dots (BNQDs) were prepared with excellent photoelectric property and low toxicity. After its structure and electrochemical property were investigated in detail, it was noted that the ECL signal of Ru(Phen)32+ could be strengthened by the proposed BNQDs, which was further activated by ten's times in the presence of CAP. Under the optimized conditions, there was an excellent linear relationship between △ECL and lgcCAP in a wide linear range from 1.0×10-10 to 1.0×10-6 mol/L CAP. The detection limit was super-low to be 3.3×10-11 mol/L (S/N=3). When applied for CAP detection in real pharmaceutical and food samples, the recoveries were between 97.8 and 105.7 % with R.S.D. less than 3.3%. A possible CAP-activated ECL mechanism of BNQDs-Ru(phen)32+ was also proposed. This work will offer a great potential for efficient monitoring of CAP pollution and clinical diagnosing of CAP-related diseases in future.

7.
Med Sci Monit ; 28: e937928, 2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36372993

RESUMEN

BACKGROUND This study aimed to analyze the clinical characteristics of tracheobronchial foreign bodies in children in Shenzhen and to explore the diagnosis and treatment methods for special cases. MATERIAL AND METHODS This study included a total of 715 children who were diagnosed with tracheobronchial foreign bodies at Shenzhen Children's Hospital between October 2016 and October 2021. Data on sex, age, inducement, symptoms, foreign body type, foreign body location, foreign body retention time, foreign body history, and complications were recorded and analyzed. RESULTS Tracheal foreign bodies were found to occur primarily in children aged 0-2 years (90.6%). The overall incidence rates were 69.1% and 30.9% in boys and girls, respectively. Among them, 42.5% of the foreign bodies were detected in the left bronchus and 45.6% in the right bronchus. Inducements included playing while eating (n=398, 55.7%) and also crying (n=209, 29.2%). Operations were performed on 710 (99.3%) children, including 80 (11.2%) immediate surgeries and 2 tracheotomies. One child had no vital signs upon admission and died after emergency foreign body removal. All of the other children who underwent surgery recovered well postoperatively. CONCLUSIONS This study presents the characteristics and methods of diagnosis and treatment of tracheobronchial foreign bodies in pediatric patients in Shenzhen. Tracheobronchial foreign bodies are a major cause of accidental injury in infants and young children. In critical cases, airways should be immediately and rapidly cleared with multidisciplinary collaboration. In addition, public safety awareness should be strengthened, particularly among parents, teachers, and other child caregivers, to reduce and prevent instances of tracheobronchial foreign body accidents in children.


Asunto(s)
Broncoscopía , Cuerpos Extraños , Lactante , Masculino , Femenino , Niño , Humanos , Preescolar , Broncoscopía/métodos , Estudios Retrospectivos , Cuerpos Extraños/epidemiología , Cuerpos Extraños/terapia , Bronquios , Tráquea/cirugía
8.
Am J Otolaryngol ; 43(3): 103380, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35256206

RESUMEN

OBJECTIVE: To explore the novel technique of percutaneous endoscopic suture lateralization for bilateral vocal cord paralysis (BVCP) in neonates from Shenzhen, China, and to evaluate the safety and efficacy of the operation. METHODS: In this retrospective case series, we present four neonates with BVCP diagnosed within 3 days after birth from Shenzhen Children's Hospital. All had stridor, respiratory distress and hypoxemia requiring respiratory support at diagnosis. Endoscopic vocal fold lateralization was performed under general anesthesia using 3.0 mm endotracheal intubation through the improved technique of percutaneous needle-directed placement of a 4-0 Prolene suture, without the use of specialized equipment. A 4-0 Prolene wire was led out through two 10 ml syringe needles, the left vocal cord was fully moved and fixed under the skin with endoscopy monitoring. RESULTS: Overall, 3/4 of the patients showed clinical improvement in stridor and dyspnea 2-3 weeks after the operation and avoided a tracheostomy, two of them could breathe and feed normally when they were discharged from hospital, and one patient had a weak ability to suck but could breathe normally. The last patient had to undergo a tracheotomy due to the poor improvement in respiratory distress. None of the babies experienced any complications from this surgery, but case four presented with a series of complications and other problems in postoperative care related to the tracheostomy. At the last follow-up (mean 8 months), complete function of the bilateral vocal cords was acquired in case two (6 months) and partial function of the vocal cords was acquired in case one (13 months), with the other cases still experiencing paralysis. CONCLUSION: Endoscopic percutaneous suture lateralization may be a reversible, effective and minimally invasive primary treatment for neonatal BVCP. Most of neonates with BVCP undergoing this procedure avoided a tracheotomy.


Asunto(s)
Endoscopía , Técnicas de Sutura , Parálisis de los Pliegues Vocales , Disnea/cirugía , Humanos , Recién Nacido , Agujas , Polipropilenos , Síndrome de Dificultad Respiratoria , Ruidos Respiratorios , Estudios Retrospectivos , Técnicas de Sutura/efectos adversos , Jeringas , Parálisis de los Pliegues Vocales/cirugía , Pliegues Vocales
9.
Inorg Chem ; 60(4): 2563-2572, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33494596

RESUMEN

Recently, metal-organic frameworks (MOFs) have been investigated as potential materials for CO2 capture and light hydrocarbon storage/separation due to their high porosity, large surface area, and tunable skeleton structures. In this work, the six cobalt-based MOFs 1-6 were successfully synthesized under solvothermal conditions by a mixed-ligand strategy. 1 and 2 have the same framework structure with a topology of {42·5}2{44·510·67·76·8}, while the structures of the 3-6 frameworks are the same with a topology of {42·5}2{44·510·69·74·8}. The adsorption properties of these MOFs for CO2 and C2 hydrocarbons were then investigated, and the effect of the functional groups was discussed. The results revealed that the introduction of amino and bromo groups could effectively strengthen the adsorption performance.

10.
Acta Pharmacol Sin ; 42(5): 755-766, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32855529

RESUMEN

ß-arrestin2 (ß-arr2) is, a key protein that mediates desensitization and internalization of G protein-coupled receptors and participates in inflammatory and immune responses. Deficiency of ß-arr2 has been found to exacerbate collagen antibody-induced arthritis (CAIA) through unclear mechanisms. In this study we tried to elucidate the molecular mechanisms underlying ß-arr2 depletion-induced exacerbation of CAIA. CAIA was induced in ß-arr2-/- and wild-type (WT) mice by injection of collagen antibodies and LPS. The mice were sacrificed on d 13 after the injection, spleen, thymus and left ankle joints were collected for analysis. Arthritis index (AI) was evaluated every day or every 2 days. We showed that ß-arr2-/- mice with CAIA had a further increase in the percentage of plasma cells in spleen as compared with WT mice with CAIA, which was in accordance with elevated serum IgG1 and IgG2A expression and aggravating clinical performances, pathologic changes in joints and spleen, joint effusion, and joint blood flow. Both LPS stimulation of isolated B lymphocytes in vitro and TNP-LPS challenge in vivo led to significantly higher plasma cell formation and antibodies production in ß-arr2-/- mice as compared with WT mice. LPS treatment induced membrane distribution of toll-like receptor 4 (TLR4) on B lymphocytes, accordingly promoted the nuclear translocation of NF-κB and the transcription of Blimp1. Immunofluorescence analysis confirmed that more TLR4 colocalized with ß-arr2 in B lymphocytes in response to LPS stimulation. Depletion of ß-arr2 restrained TLR4 on B lymphocyte membrane after LPS treatment and further enhanced downstream NF-κB signaling leading to additional increment in plasma cell formation. In summary, ß-arr2 depletion exacerbates CAIA and further increases plasma cell differentiation and antibody production through inhibiting TLR4 endocytosis and aggravating NF-κB signaling.


Asunto(s)
Artritis Experimental/metabolismo , Artritis Reumatoide/metabolismo , Células Plasmáticas/metabolismo , Arrestina beta 2/deficiencia , Animales , Anticuerpos Monoclonales/inmunología , Artritis Experimental/inducido químicamente , Artritis Experimental/patología , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/patología , Peso Corporal/fisiología , Diferenciación Celular/fisiología , Colágeno Tipo II/inmunología , Inmunidad Humoral/fisiología , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Activación de Linfocitos/fisiología , Masculino , Ratones Endogámicos C57BL , Transducción de Señal/fisiología , Receptor Toll-Like 4/metabolismo
11.
Chemistry ; 26(10): 2154-2158, 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-31803978

RESUMEN

Metal-organic rotaxane frameworks (MORFs) attracted much attention in the past years for construction of intelligent functional materials. Herein, a one-pot synthesis is reported of a three-dimensional (3D) cucurbit[7]uril (Q[7])-based MORF under hydrothermal conditions, namely Q[7]-MORF-1, formed by encapsulating the anionic benzoate moieties of the tricarboxylate ligand into the cavity of Q[7]. Furthermore, Q[7]-MORF-1 shows dual-capture capacity for iodine and K+ selectively among the alkali metal ions. The captured molecular iodine is included in the cavity of Q[7] through halogen-bonding interactions and the K+ cations are positioned at the carbonyl port of the Q[7] through K-O coordination interactions.

12.
J Am Chem Soc ; 141(1): 76-79, 2019 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-30585063

RESUMEN

Rh(III)-catalyzed meta-C-H functionalization reactions are still rare. Herein, we report the first example of Rh(III)-catalyzed meta-C-H alkenylation with disubstituted alkynes directed by a U-shaped nitrile template. Exclusive regio-selectivity has been achieved using unsymmetrical aryl and alkyl-disubstituted alkynes to afford synthetically valuable trisubstituted olefins. Propargyl alcohols are also compatible, affording complex allylic alcohols. Notably, transition metal-catalyzed meta-alkenylation with alkynes has not been successful with Pd catalysts.

13.
Angew Chem Int Ed Engl ; 58(27): 9099-9103, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31124280

RESUMEN

A ligand-promoted RhIII -catalyzed C(sp2 )-H activation/thiolation of benzamides has been developed. Using bidentate mono-N-protected amino acid ligands led to the first example of RhIII -catalyzed aryl thiolation reactions directed by weakly coordinating directing amide groups. The reaction tolerates a broad range of amides and disulfide reagents.

14.
J Am Chem Soc ; 139(6): 2200-2203, 2017 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-28128942

RESUMEN

A range of Rh(III)-catalyzed ortho-C-H functionalizations have been developed; however, extension of this reactivity to remote C-H functionalizations through large-ring rhodacyclic intermediates has yet to be demonstrated. Herein we report the first example of the use of a U-shaped nitrile template to direct Rh(III)-catalyzed remote meta-C-H activation via a postulated 12-membered macrocyclic intermediate. Because the ligands used for Rh(III) catalysts are significantly different from those of Pd(II) catalysts, this offers new opportunities for future development of ligand-promoted meta-C-H activation reactions.

15.
Angew Chem Int Ed Engl ; 56(26): 7449-7453, 2017 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-28500664

RESUMEN

Ligand development for rhodium(III)-catalyzed C-H activation reactions has largely been limited to cyclopentadienyl (Cp) based scaffolds. 2-Methylquinoline has now been identified as a feasible ligand that can coordinate to the metal center of Cp*RhCl to accelerate the cleavage of the C-H bond of N-pentafluorophenylbenzamides, providing a new structural lead for ligand design. The compatibility of this reaction with secondary free amines and anilines also overcomes the limitations of palladium(II)-catalyzed C-H amination reactions.

16.
Inorg Chem ; 55(22): 11821-11830, 2016 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-27934302

RESUMEN

Metal-organic frameworks (MOFs) have attracted great attention in the past years due to their diverse structures as well as interesting properties. However, MOFs with multifunctionality are still challenging. Under solvothermal conditions, reactions of 1,3,5-tris(1-imidazolyl)benzene (tib) and 4,4',4″-benzene-1,3,5-triyl-tribenzoic acid (H3BTB) with Cd(II) salt give rise to two novel MOFs [Cd3(tib)2(BTB)2]·3DEF·4.5H2O (1) and [Cd3(tib)2(BTB)2(DMA)2(H2O)2]·2DMA·8H2O (2) (DEF = N,N-diethylformamide, DMA = N,N-dimethylacetamide) with three-dimensional framework structures. It is fascinating that 1 and 2 not only show unique selectivity for detection of acetone through fluorescence quenching mechanism but also exhibit selective adsorption of gas (CO2 over N2 at 298 K) and dye (methyl orange) molecules.

17.
Acta Pharmacol Sin ; 36(11): 1367-76, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26456588

RESUMEN

AIM: A number of evidence shows that the differentiation of B lymphocytes into plasma cells plays an important role in lupus pathogenesis. In this study we investigated how prednisone, a classical therapeutic drug for autoimmune diseases, regulated plasma cell differentiation in MRL/MpSlac-lpr mice. METHODS: MRL/lpr mice were treated with prednisone (2.5 or 5 mg·kg(-1)·d(-1), ig) for 13 weeks, and the proteinuria levels and survival times were monitored. After the mice were euthanized, blood sample, spleen and thymus were collected. The serum levels of anti-dsDNA antibody, anti-nuclear antibody, IL-21, and IL-10 were detected using ELISA kits. Subsets of splenic B and T lymphocytes were quantified with flow cytometry. Transcription factor Blimp-1 and Bcl-6 expression was determined using qPCR and Western blot. RESULTS: Prednisone treatment dose-dependently attenuated the lupus symptoms in MRL/lpr mice with decreased proteinuria levels, prolonged survival times, decreased serum anti-nuclear antibody levels, and reduced spleen and thymus indices. Prednisone treatment also significantly decreased the elevated percentages of plasma cells and plasma cell precursors, decreased the percentages of activated T cells, and increased the frequency of CD4(+)CD62L(+) cells, demonstrated that decreased anti-nuclear antibodies and improvements in lupus symptoms were associated with decreased plasma cells. Furthermore, prednisone treatment decreased serum IL-21 and IL-10 levels and reduced the expression of splenic Blimp-1 and Bcl-6 (two key regulatory factors for plasma cell differentiation) in MRL/lpr mice. CONCLUSION: Prednisone treatment restricts B lymphocyte differentiation into plasma cells in MRL/lpr mice, which may be correlated with the inhibition of IL-21 production and the restoration of the balance between Blimp-1 and Bcl-6.


Asunto(s)
Antiinflamatorios/uso terapéutico , Linfocitos B/efectos de los fármacos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Células Plasmáticas/efectos de los fármacos , Prednisona/uso terapéutico , Animales , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Linfocitos B/inmunología , Linfocitos B/patología , Diferenciación Celular/efectos de los fármacos , Citocinas/sangre , Citocinas/inmunología , Femenino , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Ratones Endogámicos MRL lpr , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Proteinuria/complicaciones , Proteinuria/tratamiento farmacológico , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/patología , Timo/efectos de los fármacos , Timo/inmunología , Timo/patología
18.
J Am Chem Soc ; 136(48): 16744-7, 2014 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-25397917

RESUMEN

Multidimensional supramolecular assemblies based on cucurbit[n]uril (n = 6 or 7) were constructed via the outer-surface interactions of cucurbit[n]urils with the polyaromatic compound 4,4',4″-benzene-1,3,5-triyl-tribenzoate as a structure-directing agent. Most impressively, the cucurbit[6]uril-based assembly exhibits high selectivity for capture of cesium cations among the common alkali metal ions in a basic medium and releases the cesium cations under acidic conditions. This reversible process enables possible applications in cesium cation capture.

19.
Laryngoscope ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189311

RESUMEN

PURPOSE: Bilateral vocal fold paralysis (BVFP) is a critical condition in newborns, which may present with significant airway distress necessitating tracheostomy. The purpose of this study is to report the safety and effectiveness of endoscopic percutaneous suture lateralization (EPSL) for newborns with BVFP, and evaluated the long-term results and the stability of the lateralization. METHODS: A review of patients undergoing EPSL for BVFP at our institutions was performed between October 2018 and June 2023. Preoperative and postoperative clinical information was collected. The functional outcomes of the surgery in terms of breathing, voice, and swallowing were evaluated and recorded. RESULTS: Twenty seven patients were included, with a median age at diagnosis of 12 days (range, 1-33 days). The maximum follow-up is for 5 years. EPSL was successful in 77.8% of cases, effectively avoiding the need for tracheostomy. Dyspnea was relieved within a month after surgery, enabling patients to tolerate oral feeds within 2 months after surgery. Notably, some patients experienced a return of vocal fold function, particularly in successful EPSL cases, underlining the procedure's efficacy. Minor complications, including granulation tissue and wound infection, were observed but were manageable. Major complications were notably absent. The results are durable and stable at long-term follow-up. CONCLUSION: EPSL for BVFP is a relatively simple, minimally invasive, non-destructive, safe, and effective procedure in newborns, which may avoid the need for a tracheostomy, preserves the laryngeal framework, and does not affect the natural recovery of vocal cords. LEVEL OF EVIDENCE: Level 3: retrospective case series Laryngoscope, 2024.

20.
Chemosphere ; 363: 142885, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39025314

RESUMEN

Particulate matter of aerodynamic diameter ≤2.5 µm (PM2.5) exposure induces oxidative stress in lung tissues. Ferroptosis is a form of regulated cell death based on oxidative damage and lipid peroxidation. Whether PM2.5 exposure-induced oxidative stress can promote ferroptosis to aggravate asthma is not known. To investigate if PM2.5 exposure induces oxidative stress to promote ferroptosis and influence asthma development, a cockroach extract-induced asthma model in mice was used for in vivo studies. Airway epithelial cell (AEC) ferroptosis was detected by assays (CCK8, malonaldehyde, and 4-hydroxynonenal). Molecular mechanisms were investigated by real-time reverse transcription-quantitative polymerase chain reaction, western blotting, flow cytometry, liquid chromatography-tandem mass spectrometry, and chromatin immunoprecipitation. We found that exposure to PM2.5 and Indeno[1,2,3-cd] pyrene (IP; one of the prominent absorbed polycyclic aromatic hydrocarbons in PM2.5) enhanced the sensitivity of AECs to ferroptosis to aggravate asthma, whereas ferroptosis inhibitors and cytosolic phospholipase A2 (cPLA2) inhibitors reversed this augmented inflammatory response in mice suffering from asthma. IP treatment enhanced cPLA2 expression/activation through aryl hydrocarbon receptor (AhR) genomic and non-genomic pathways, resulting in arachidonic-acid release to promote the sensitivity of AECs to ferroptosis. IP exposure enhanced the release of leukotriene-B4 from lung macrophages, resulting in enhanced expression of acyl-coA synthetase long chain family member4 (ACSL4) and the sensitivity of AECs to ferroptosis. This finding suggests that exposure to PM2.5 and IP promote ferroptosis sensitivity in AECs to aggravate asthma, which may provide new targets for the prevention and treatment of asthma.


Asunto(s)
Asma , Células Epiteliales , Ferroptosis , Material Particulado , Ferroptosis/efectos de los fármacos , Animales , Asma/inducido químicamente , Asma/metabolismo , Ratones , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Material Particulado/toxicidad , Estrés Oxidativo/efectos de los fármacos , Contaminantes Atmosféricos/toxicidad , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Ratones Endogámicos BALB C , Receptores de Hidrocarburo de Aril/metabolismo , Peroxidación de Lípido/efectos de los fármacos
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